CN118055742A

CN118055742A - System for shaping and implanting a biological intraocular stent for increasing water outflow and reducing intraocular pressure

Info

Publication number: CN118055742A
Application number: CN202280066262.0A
Authority: CN
Inventors: T·艾恩丘勒夫; L·克劳森; D·内尔森; D·罗伯森; D·巴克尔; S·巴克斯顿
Original assignee: Antlake
Current assignee: Antlake
Priority date: 2021-09-08
Filing date: 2022-09-08
Publication date: 2024-05-17

Abstract

A system for deploying an implant cut from biological tissue into an eye of a patient includes a delivery device and a nose cone assembly, a tubular shaft protruding from a distal region of the nose cone and including a lumen. Related apparatus, systems, and methods are provided.

Description

System for shaping and implanting a biological intraocular stent for increasing water outflow and reducing intraocular pressure

Cross Reference to Related Applications

The present application claims the priority of co-pending provisional patent applications filed on day 35U.S. C. ≡119 (e) with serial numbers No.63/241,713, serial numbers No.63/252,753, and serial numbers No.63/271,639 filed on day 10, 2021, and serial numbers No. 25, 2021, 9 filed on day 9, and 2021. The disclosures of these provisional applications are incorporated herein by reference in their entirety.

The present application is also a continuation of the application from part of U.S. application Ser. No. 17/325,785, filed 5/2021, U.S. Ser. No. 17/325,785, claims 35U.S. C. ≡20/2020 (e) to the priority of U.S. provisional patent application Ser. No.63/027,689, filed 5/20/2020, and U.S. provisional patent application Ser. No.63/163,623, filed 3/2021. The disclosures of these applications are incorporated herein by reference in their entirety.

Background

The main content of glaucoma ophthalmic surgery is to increase the outflow of water from the eye. There are various methods of such surgery, including: 1) An external trabeculectomy or shunt, which requires cutting the conjunctiva and sclera to penetrate the eye and provide a transscleral outflow path; 2) Endoprosthesis or transscleral outflow stenting or water diversion using a hardware-based implantable device or using an ablative, non-implantable cutter (e.g., dual blade and small Liang Xiaorong instrument); 3) Endoprosthesis using an implantable abiotic hardware implant.

Current endoprosthetic devices and methods are based on non-biological hardware materials such as polyimide, polyethersulfone, titanium, polystyrene block-isobutylene block-styrene, and the like. Such non-bio hardware based implantable devices have significant drawbacks because these devices can lead to severe erosion, fibrosis and ocular tissue damage, such as endothelial cell loss.

In view of the foregoing, there is a need for improved devices and methods associated with ophthalmic surgery for treating glaucoma.

Disclosure of Invention

In one aspect, a system for deploying an implant cut from biological tissue into an eye of a patient is described, the system comprising a delivery device having a proximal housing; at least one actuator; and a distal coupler. The system includes a nose cone assembly having a nose cone with a proximal region and a distal region; a coupler on the proximal region of the nose cone configured to reversibly engage with a distal coupler of the delivery device; and a tubular shaft protruding from a distal region of the nose cone and having a lumen. The tubular shaft has one or more fenestrations extending through the side wall of the shaft, the one or more fenestrations being covered with a translucent or transparent material so as to reveal the lumen of the tubular shaft.

In a related aspect, a device for minimally modifying biologically derived tissue is described that includes two blades separated by a gap, each blade having an inner face and at least one distal bevel forming a cutting edge. The two blades are mounted at an angle relative to each other such that the inner faces are not parallel and the distal slopes are parallel to each other. The device is configured to cut the biologically derived tissue into an elongated strip having a length and a width, wherein the length is greater than the width.

In a related aspect, a cassette for use with a system for preparing an implant and inserting an implant endo-route into an eye is described. The cassette includes a lower member having a planar upper surface sized and shaped to receive a piece of material to be cut into an implant; an upper member movably coupled to the lower member between an open configuration and a closed configuration, the upper member having a lower surface arranged to oppose an upper surface of the lower member when the upper member is in the closed configuration; a pair of blades configured to extend below the lower surface of the upper member to cut pieces of material into implants.

In a related aspect, a system for preparing an implant for implantation in an eye of a patient and inserting the implant into the eye of the patient is described. The system includes a cartridge configured to receive a piece of material and having a pair of blades configured to cut the piece to form an implant from the piece; and a delivery instrument having a housing and a distal portion sized and shaped for insertion into an anterior chamber of an eye. The distal portion has a lumen with an elongated tubular member sized to receive an implant cut from a blade with the pair of blades.

In a related aspect, a system for preparing an implant for implantation in an eye of a patient and inserting the implant into the eye of the patient is described. The system includes a cassette configured to receive and retain material within the cassette; at least one cutting member configured to cut a material to form an implant from the material; and a delivery instrument having a housing and a distal portion sized and shaped for insertion into an anterior chamber of an eye, wherein the distal portion includes a lumen having an elongated tubular member.

In a related aspect, a system for preparing an implant and inserting an implant endo-route into an eye is described. The system includes a blade cartridge configured to move between an open configuration and a closed configuration for loading a piece of material into the cartridge. The cartridge includes a lower member having an upper surface configured to receive a piece of material; an upper member having a lower surface configured to abut against a patch of the material when the cassette is in the closed configuration; and a pair of blades and a spacer defining a gap between the blades. The pair of blades are configured to extend below the lower surface of the upper member to penetrate the piece of material at two locations to form a strip of material having a width narrower than the width of the piece of material when the blade cartridge is moved into the closed configuration.

In a related aspect, a system for deploying an implant cut from biological tissue into an eye of a patient is described. The system includes a delivery device having a proximal housing; at least one actuator coupled to the pushrod; and a distal coupler. The system includes a nose cone assembly having a nose cone with a proximal region and a distal region; a coupler on the proximal region of the nose cone configured to reversibly engage with a distal coupler of the delivery device; and a tubular shaft protruding from a distal region of the nose cone and including a lumen, the tubular shaft including a distal region and a proximal region. The distal region is curved away from the longitudinal axis of the proximal region.

In some variations, one or more of the following may optionally be included in any feasible combination of the above-described methods, apparatus, devices, and systems. Further details are set forth in the accompanying drawings and the description below. Other features and advantages will be apparent from the description and drawings.

Drawings

These and other aspects will now be described in detail with reference to the following drawings. Generally, the drawings are not to absolute or relative scale, but are intended to be illustrative. Furthermore, the relative placement of features and elements may be modified for clarity of illustration.

FIGS. 1A-1B are cross-sectional views of a human eye showing the anterior chamber and vitreous chamber of the eye with a stent in an exemplary position in the eye;

FIG. 2 is a perspective view of a system according to one embodiment;

FIGS. 3A and 3B illustrate an embodiment of a tissue cassette of the system of FIG. 2 with a cover removed;

FIG. 3C shows the tissue cassette of FIGS. 3A-3B with a cover mounted;

FIG. 4A illustrates the cutting device of the system of FIG. 2 with a tissue cassette mounted and a cutter in an open configuration;

FIG. 4B illustrates the cutting device of FIG. 4A with a tissue cassette mounted and a cutter in a cutting configuration;

FIG. 4C is a partial view of the cutting device of FIG. 4B, showing a cutter;

FIG. 4D is a partial cross-sectional view of the cutting device of FIG. 4A;

FIG. 4E is a partial cross-sectional view of the cutting device of FIG. 4B;

FIGS. 4F-4G illustrate the pusher of the cutting device of FIG. 4A in an advanced and retracted configuration, respectively, relative to the base of the cutting device;

FIG. 4H is a cross-sectional view of the cutting device of FIG. 4G;

FIGS. 4I-4J are partial cross-sectional views of the cutting device of FIG. 4F;

FIG. 5A illustrates the delivery device of the system of FIG. 2 with a tissue cassette mounted and a pusher in an advanced configuration;

FIG. 5B shows the delivery device of FIG. 5A with the cassette withdrawn relative to the pusher;

FIG. 5C illustrates the tissue cassette of FIG. 5A and a distal region of the delivery device;

FIG. 5D shows a tissue cassette installed within the delivery device of FIG. 5C;

FIG. 5E shows the pusher of the delivery device of FIG. 5A advanced to a deployed position;

FIG. 5F shows the tissue cassette retracted by the delivery device to deploy the cut scaffold within the eye;

FIG. 6 is a perspective view of a system according to a related embodiment;

FIGS. 7A and 7B illustrate the tissue cassette of FIG. 6 with the cover in a stowed configuration;

FIG. 7C illustrates the tissue cassette of FIGS. 7A-7B with a cover mounted;

FIG. 8 illustrates the cutting device and tissue cassette of FIG. 6;

FIG. 9A illustrates one embodiment of a cutting device with a tissue cassette mounted, the cutter in a cutting configuration, and the nose cone of the tissue cassette separated;

FIG. 9B illustrates one embodiment of a delivery device having a nose cone of an engaged tissue cassette with the pusher in a retracted configuration;

FIG. 9C shows the delivery device of FIG. 9B with the pusher advanced to the ready configuration;

FIG. 9D shows the delivery device of FIG. 9C with the nose cone retracted relative to the pusher;

FIG. 10A shows the nose cone prior to engagement with the distal end region of the delivery device;

FIG. 10B shows the nose cone after engagement with the distal end region of the delivery device and prior to attachment;

FIG. 10C shows a nose cone engaged and attached to a distal region of a delivery device;

FIG. 11A shows the pusher of the delivery device of FIG. 10A in a first retracted position;

FIG. 11B shows the pusher of the delivery device of FIG. 10A advanced to a second ready position;

FIG. 11C shows the distal shaft of the delivery device of FIG. 10A positioned within the eye and a third actuator ready to be actuated;

FIGS. 12A-12B are cross-sectional views of the delivery device of FIG. 10A showing the first retracted position of FIG. 11A;

FIGS. 12C-12D are cross-sectional views of the transfer device of FIG. 10A showing the second ready position of FIG. 11B;

FIGS. 13A-13B illustrate a reset mechanism of the transfer device of FIG. 10A;

FIGS. 14A-14H illustrate stages of use of different embodiments of a cutting assembly for cutting a scaffold and transferring the scaffold to a portion of a tissue cassette;

FIG. 14I schematically illustrates an embodiment of a nose cone assembly coupled to a cutting assembly;

15A-15B illustrate another embodiment of a cutting device for cutting a stent;

FIG. 16A is a side view of an embodiment of a nose cone assembly;

FIG. 16B is a distal view of the distal tip taken along arrows B-B in FIG. 16A;

FIG. 16C is a detailed view of the distal end region of the distal shaft of FIG. 16A taken at circle A;

FIG. 17A shows the proximal housing of the delivery device of FIG. 10A with a keyed coupling for receiving the nose cone assembly;

17B-17C illustrate the nose cone assembly of FIG. 16A for coupling with the proximal housing of FIG. 17A from a front end view and a rear end view, respectively;

FIG. 17D illustrates a nose cone assembly coupled with a proximal housing;

FIG. 17E shows a detailed view of the distal shaft of the nose cone assembly of FIG. 16A with the pusher visible in the bevel;

FIG. 17F shows a detailed exploded view of the distal shaft and pushrod;

17G-17H are partially transparent views of the actuator in a ready position;

FIG. 17I is a perspective view of an actuator having a flexure (flexture);

FIG. 18A illustrates an embodiment of a cutting device;

FIG. 18B shows the cutting device of FIG. 18A with the handle articulated to an open configuration;

FIG. 18C shows the cutting device of FIG. 18B with the pressure pad in an open configuration, thereby revealing a bearing surface;

FIG. 18D is a detailed view of the cutting device of FIG. 18C;

FIG. 18E is a schematic view of a cutting assembly of the cutting device of FIG. 18A;

FIG. 18F is a perspective view of the associated cutting device of FIG. 18A;

FIG. 18G is a cross-sectional view of the device of FIG. 18F taken along line G-G;

FIG. 18H is a detailed view of a dual blade of the device of FIG. 18F;

FIG. 19A is an embodiment of the loading device prior to coupling the nose cone assembly to the receptacle;

FIG. 19B is an embodiment of the loading device after coupling the nose cone assembly to the receptacle;

FIGS. 20A-20B are schematic cross-sectional views of a loading device for aligning and compressing a cut stent prior to loading the cut stent into a delivery shaft;

FIG. 21A is a perspective view of an embodiment of a trephine device engaged with a blade cartridge;

FIG. 21B is a perspective view of the trephine device of FIG. 21A with the blade cartridge uncoupled;

FIG. 22A is an end view of the trephine device of FIG. 21A showing the blades of the blade cartridge relative to the bearing surface;

FIG. 22B is a detailed view of the blade of the trephine device of FIG. 21A;

FIG. 22C is a detailed view of the cutting edge of the blade of FIG. 22B taken at circle C;

FIG. 22D shows a single bevel blade;

FIG. 22E shows a double bevel blade;

fig. 23A-23C are perspective and end views of an ejector spring between the blades of the blade cartridge of the trephine device of fig. 21A.

It should be understood that the drawings are merely exemplary and are not intended to be drawn to scale. It is to be understood that the devices described herein may include features that are not necessarily depicted in each figure.

Detailed Description

Implants, systems, and methods for increasing outflow of water from the anterior chamber of an eye are disclosed. As will be described in detail below, endooutflow stenting using biological, cell-based or tissue-based materials provides biocompatible water outflow enhancement with improved tolerability and safety compared to conventional shunts. In one exemplary embodiment, a cutting device, also referred to herein as a trephine device or cutting tool, is used to harvest or produce biological tissue or biologically derived material in vitro and form an implant, also referred to herein as a scaffold. In one embodiment, the stent is an elongated body or material having a lumen to provide a passageway for drainage. In a preferred embodiment, the stent is an elongate body or tissue strip that is free of lumens and is configured to hold a split and provide supraciliary stenting (or stenting in another anatomical location such as in schlemm's canal or transscleral). Lumen-based devices may be limited by the lumen as a fibrotic occlusion channel. The scaffold formed from the tissue is then implanted into the eye through the internal delivery passageway to provide outflow of water from the anterior chamber. The stents described herein may be used as Minimally Invasive Glaucoma Surgery (MIGS) treatments as phacoemulsification aids or as stand alone treatments for glaucoma.

The use of terms such as stent, implant, shunt, biological tissue or tissue is not intended to be limiting of any one structure or material. The implanted structure may, but need not, be a material that is substantially absorbed into the ocular tissue after placement in the eye, such that once absorbed, space may remain at the location where the structure was previously located. Once implanted, the structure may also remain in place for an extended period of time and may not substantially erode or absorb.

As will be described in greater detail below, the stents described herein may be made of biologically derived materials that do not cause toxic or damaging effects after implantation in a patient.

The term "biologically derived material" includes naturally occurring biological materials and synthetic biological materials suitable for implantation in the eye, as well as combinations thereof. Biologically derived materials include materials that are natural biological structures having a biological arrangement that occurs naturally in a mammalian subject, including organs or organ portions formed from tissue, and tissues formed from materials that are combined together in terms of structure and function. Biologically derived materials include tissues such as cornea, sclera, or cartilage tissue. Tissues contemplated herein may include any of a variety of tissues including muscle, epithelial, connective, and neural tissues. Biologically derived materials include tissues, organs, organ portions and tissues from subjects harvested from a donor or patient, including a piece of tissue suitable for transplantation, including autograft, allograft and xenograft materials. Biologically derived materials include naturally occurring biological materials, including any materials naturally occurring in the mammalian body. Biologically derived materials as used herein also include materials engineered to have a biological arrangement similar to that of the natural biological structure. For example, the material may be synthesized using in vitro techniques, such as by seeding a three-dimensional scaffold or matrix with appropriate cellular, engineered, or 3D printed materials to form a biological structure suitable for implantation. Biologically derived materials as used herein also include cell derived materials, including stem cell derived materials. In some embodiments, the biologically derived material comprises an injectable hyaluronate hydrogel or a viscous material, such as GEL-ONE crosslinked hyaluronate (Zimmer).

The biologically derived material may include naturally occurring biological tissue, including any material naturally occurring in a mammal, which is minimally manipulated or more than minimally manipulated according to FDA guidelines at 21CFR 1271.3 (f) such that processing biological tissue does not alter the relevant biological properties of the tissue (see regulatory notice of human cells, tissue, and cell and tissue products: minimal manipulation and homologous use (Regulatory Considerations for Human Cells,Tissues,and Cellular and Tissue-Based Products:Minimal Manipulation and Homologous Use)",www.fda.gov/regulatory-information/search-fda-guidance-documents/regulatory-considerations-human-cells-tissues-and-cellular-and-tissue-based-products-minimal).

In some embodiments, the bioscaffold may be an engineered or 3D printed material formed into a tube shape having a lumen extending from a proximal opening to a distal opening. The tube may also be printed to incorporate multiple openings throughout. For example, the walls of the printing material may be designed with a plurality of openings so that liquid within the lumen can seep or flow outwardly through the walls of the tube so that the tube is sufficiently porous to ensure drainage of water from the eye. The tube may be printed with dimensions modified at or near delivery. For example, the 3D printed material may be designed to have a first size that facilitates manual handling. At or near delivery, the 3D printed material may be cut to a size more suitable for implantation into the eye. Where a patch of material is described as being cut or trephined into a stent prior to implantation, it will be appreciated that the patch of material may be a printed material having a particular 3-dimensional shape (e.g. including tubular) and cut into a stent by cutting to a shorter desired length. Thus, in certain embodiments, the stents described herein need not be solid and may also incorporate lumens.

The bio-derived material used to form the scaffold, sometimes referred to herein as biological tissue or biomaterial, may vary and may be, for example, corneal tissue, scleral tissue, cartilage tissue, collagen tissue, or other hard biological tissue. Biological tissue may be hydrophilic or hydrophobic. The biological tissue may include or be impregnated with one or more therapeutic agents for additional treatment of the ocular disease process.

The biological stent material may be used in combination with one or more therapeutic agents so that it may be used to additionally deliver the agent to the eye. In one embodiment, the biological tissue may be embedded with slow release pellets, or immersed in a therapeutic agent, for slow release delivery to the target tissue.

Non-biological materials include synthetic materials prepared by artificial synthesis, processing or manufacture, which may be biocompatible, but are not cell-based or tissue-based. For example, non-biological materials include polymers, copolymers, polymer blends, and plastics. Non-biological materials include inorganic polymers such as silicone rubber, polysiloxanes, polysilanes; and organic polymers such as polyethylene, polypropylene, polyethylene compounds, polyimide, and the like.

Regardless of the source or type of biologically derived material, the material may be cut or trephine into an elongated shape suitable for stenting and implantation into the eye. The cutting process of the tissue may be performed prior to the surgical implantation process or during the surgical implantation process. The stent(s) implanted in the eye may have a structure and/or permeability that allows water to flow from the anterior chamber when positioned within the ciliary separation tear.

The biologically derived material may be minimally modified or minimally manipulated tissue for the eye. Minimally modified biologically derived materials do not involve the combination of the material with another article, except for example, water, bactericides, preservatives, cryoprotectants, storage agents and/or drug or therapeutic agent(s), and the like. Minimally modified biologically derived materials, once implanted, do not produce systemic effects and their primary function is independent of the metabolic activity of any living cell. During each step of the method of preparation and use, the biologically derived material can be minimally manipulated so as to preserve the original relevant characteristics of the biological tissue. The cut scaffold may be a physical support or structural tissue that acts as a barrier or conduit, for example, by at least partially retaining a ciliary breach formed in the eye. Cutting stents from bio-derived materials may be minimally manipulated by compression, compaction, folding, rolling or other types of temporary manipulation of the cut stent, which, once released from the forces applied to compress or compact, allows the material to resume its original configuration. Thus, a minimal manipulation may temporarily mechanically change the size or shape of the cut tissue while still maintaining the original relevant characteristics of the tissue once the mechanical change is removed, which characteristics relate to its utility for reconstruction, repair or replacement. For example, the biologically derived material may be the sclera, which is cut into an oversized shape relative to the inner diameter of the delivery tube through which the scaffold is implanted. Minimal manipulation of the cut scaffold may include temporarily compacting the scleral material into the lumen of the delivery shaft such that, after implantation in the eye, the cut scaffold tends to resume toward its original cut size. Although the bio-derived materials described herein are described in the context of being cut into stent-like implants that can maintain a split for water outflow, other methods are contemplated herein. For example, the bio-derived material may be compressed into a plug, which is then implanted into a region of the eye for other purposes, such as stenting, traumatic ruptured occlusion, over-filtered air bubbles, posterior wall rupture, and other indications.

Minimal structural modification of biological tissue (e.g., scleral tissue or corneal tissue) or other biological tissue (crosslinked or uncrosslinked) for implantable intraocular use may include longitudinal trephine into an elongated tissue strip having a width less than its length, e.g., the length may be greater than 2mm and less than 30mm and the thickness may be between about 0.1mm and 2.0mm and the width may be between about 0.1mm and 2.0mm prior to loading within the delivery shaft. As will be described in greater detail herein, the cutting of biological tissue allows for adjustment of the width being cut and can simultaneously compress the biological tissue to a specific, consistent thickness. The cut biological tissue may be loaded in a shuttle (cartridge) manner that compresses the biological tissue into a delivery channel for loading into, for example, a nose cone assembly or cartridge as described herein. The loading assembly may include features and linkages (links) that prevent the pusher from buckling as it transfers biological tissue from the loader into the shuttle. The cutting, loading and transferring for transfer may be combined within a single assembly or may be performed by separate assemblies configured to work in conjunction with each other. One or more components of the assemblies described herein may be provided as a ready-to-use article. For example, biological tissue may be pre-cut and provided within a preloaded shuttle assembly that is sold, for example, as a ready-to-use assembly or as a partial ready-to-use component coupled to a delivery handpiece (DELIVERY HAND PIECE).

Fig. 1A-1B are cross-sectional views of a human eye showing the anterior chamber AC and vitreous chamber VC of the eye. The stent 105 may be positioned within the eye at the implantation site such that at least a first portion of the stent 105 is positioned in the anterior chamber AC and a second portion of the stent 105 is positioned within tissue, such as within the supraciliary and/or suprachoroidal spaces (supraciliary space) of the eye. The bracket 105 is sized and shaped so that the bracket 105 can be positioned in such a configuration. The stent 105 provides or otherwise serves as a passageway for aqueous flow away from the anterior chamber AC (e.g., to the supraciliary and/or suprachoroidal space). In fig. 1A-1B, the stent 105 is schematically represented as an elongated body relative to the delivery shaft 210. It should be appreciated that the size and shape of the bracket 105 may vary. Further, the size and shape of the stent 105 prior to insertion of the delivery shaft 210 may change upon insertion of the delivery shaft 210 and may change after deployment from the delivery shaft 210.

The stent 105 may be implanted by an internal passageway (ab interno), for example, through a clear corneal incision or scleral incision. The scaffold may be implanted to create an opening or breach to enhance outflow communication between the anterior chamber AC and the supraciliary cavity, the anterior chamber AC and the suprachoroidal cavity, the anterior chamber AC and Schlemm's (Schlemm) canal or the anterior chamber AC and the subconjunctival cavity, or any other ocular compartment, tissue or interface in which transscleral, sub-scleral, or suprascleral occlusion, scaffold placement, and/or tissue enhancement is clinically indicated. In a preferred embodiment, the stent 105 is implanted such that the distal end is positioned in an supraciliary position and the proximal end is positioned in the anterior chamber AC to provide an supraciliary rupture. The distal end of the stent 105 may be positioned between other anatomical portions of the eye.

Conventional glaucoma stent devices are typically made of non-biological materials, such as polyimide or other synthetic materials, which can cause damage to the endothelial tissue, resulting in progressive, long-term, and irreversible loss of corneal endothelium. The scaffold materials described herein may reduce and/or eliminate the risk of these tissue injuries while still providing enhanced aqueous outflow.

The stent 105 described herein may be formed from any of a variety of bio-derived materials having a permeability and/or structure that allows water to be filtered therethrough. The stent 105 may be formed from a bio-derived material that is harvested, engineered, grown, or otherwise fabricated. The bio-derived scaffold material may be obtained or harvested from a patient or donor. The bio-derived scaffold material may be collected pre-operatively or during surgery. The bio-derived scaffold material may be a synthetic biological tissue produced using in vitro techniques. The biologically derived material may be stem cell derived or bioengineered. Tissue may be produced by in situ cell or non-cell growth. In one example embodiment, the tissue may be 3D printed during manufacturing. The biologically derived material may be minimally manipulated and retain its original structural characteristics as tissue.

The 3D printed tissue may be printed as a patch of larger material, which is then cut at the time of surgery, as described elsewhere herein. Alternatively, 3D printed tissue may be printed to have the dimensions of the final implantable stent. In this embodiment, the 3D printed material need not be cut prior to implantation, but may be directly implanted. For example, the 3D printing support may be printed directly into a cassette configured to be operatively coupled with a delivery device as described herein, which in turn is used to deploy the 3D printing support into the eye. This can be done using Biofabrication (bio-manufacturing), 2019;11 The 3D printing process described in (3) generates a 3D printing support.

In an example embodiment, the scaffold 105 is made of biological tissue. The biologically derived material may be corneal tissue and/or non-corneal tissue. The biologically derived material may include corneal, scleral, collagen, or cartilage tissue. In one embodiment, the bio-derived scaffold material may be bare corneal stromal tissue without epithelium and endothelium, which is porous and has hydrophilic permeability to allow water filtration. The biologically derived material may be the minimally manipulated sclera that retains its original structural features as tissue. The bio-derived material of the scaffold 105 may be, but need not be, incorporated into the native anatomy of the eye after placement in the eye. The scaffold may allow surrounding tissue to form a passageway that remains open for a longer period of time, even after the scaffold is absorbed. The bio-derived scaffold material may not significantly absorb or bind into the anatomy of the eye such that the scaffold 105 remains implanted for a longer period of time or indefinitely as desired.

In other embodiments, the scaffold 105 material may be made of complex carbohydrates or non-inflammatory collagen. The stent 105 may also be formed of biodegradable or bioabsorbable materials, including biodegradable polymers, including hydroxy aliphatic carboxylic acids, homopolymers or copolymers, such as polylactic acid, polyglycolic acid, polylactic glycolic acid; polysaccharides, such as cellulose or cellulose derivatives, such as ethylcellulose, sodium crosslinked or uncrosslinked carboxymethylcellulose, sodium carboxymethyl cellulose starch, cellulose ethers, cellulose esters (such as cellulose acetate, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate and calcium alginate), polypropylene, polybutyrates, polycarbonates, acrylate polymers, such as polymethacrylates, polyanhydrides, polyglutamates, polycaprolactone, such as poly-c-caprolactone, polydimethylsiloxane, polyamides, polyvinylpyrrolidone, polyvinyl alcohol phthalate, waxes (such as paraffin and white beeswax), natural oils, shellac, zein or mixtures. The stent 105 may be formed of a hyaluronate hydrogel or an adhesive material.

As described above, the bio-derived scaffold material may have a permeability or porosity that allows water filtration to adequately control or regulate intraocular pressure. Permeable biological tissue (e.g., sclera, cornea, collagen, etc.) as described herein is a preferred scaffold material, however, any biological tissue, even if impermeable, is considered herein to be a potential scaffold material for use as a structural spacer that keeps the ciliary body open. Preferably, the material of the scaffold may create a gap that allows fluid flow. The resulting gap may extend longitudinally along each side of the stent. If the material of the stent is permeable, more fluid may be separated by the ciliary body than if the stent material is impermeable and fluid needs to pass along the outside of the stent. Thus, the materials contemplated herein need not be porous to provide the desired function, however, the function may be enhanced by the porosity of the material.

Generally, the bio-derived scaffold material has a certain hardness and intraocular durability so it can maintain outflow from the anterior chamber, however, is softer compared to conventional non-bio-derived polyimide shunts (e.g., CYPASS, alcon) used to treat glaucoma. The scaffold material may have sufficient structure to act as a spacer to support the outflow on the ciliary body where opening continues. The scaffold material, once implanted within the ciliary body separation, may maintain its structural height or thickness, thereby providing fluid flow through or around the scaffold. In some embodiments, the cut stent is minimally manipulated by compression or compaction into the delivery shaft such that the size and/or shape of the cut stent is reduced from a first size to a second smaller size within the shaft. The delivery shaft may be sized and shaped for insertion into the anterior chamber through the cornea (e.g., a self-sealing incision in the cornea) and advancement toward the iridocorneal angle. The delivery shaft may deploy a compacted scaffold between the tissue layers near the angle. Once the compacted stent is deployed from the delivery shaft, it may begin to resume toward its original shape and/or size. Once implanted, the cut stent may take on a shape and/or size that is smaller than its original shape and/or size, or the same shape and/or size as its original shape and/or size. Minimally modified biological tissue may be used to treat glaucoma. The bio-derived scaffold material provides advantages in terms of biocompatibility, anatomical consistency and water permeability compared to conventional non-biological materials such as polyimide. The bio-derived scaffold material may provide better compliance and compliance to the scleral wall and less likelihood of erosion/loss of the endothelium and sclera over time and long term eye and blink.

Typically, allograft tissue used for implantation into the eye is carefully treated so as not to change its original state. The cut stents described herein do not need to be so carefully handled, but rather can be minimally modified by compression or compaction or otherwise wedging into a smaller space for delivery of the inner route into the eye for intra-ocular stenting, occlusion, reinforcement, or penetration (less than about 3.5 mm) through a corneal or scleral incision.

In one embodiment, the material used to form the stent is provided as a sheet of uncut material configured to be manually loaded into the cassette 200. The pieces of uncut material may also be cut by a cutting assembly separate from the cassette 200 and then transferred into the area of the cassette 200. As will be discussed in more detail below, the cutting may be performed at or before the operation. In some embodiments, the stent is formed by 3D printing and may be printed to the desired final dimensions for the stent, or may be printed as a piece of material that is then cut at or before surgery. The cuts achieved by the devices described herein may provide thin strips of material implantable into the eye to provide modulation of water outflow. The cutting or trephine process may position the cut implant within the catheter or lumen of the cassette so that the cut implant held within the cassette may be subsequently delivered from the delivery device without removing or transferring the cut implant from the cassette. Alternatively, the cutting may be performed independently of transferring the cut implant into the delivery device. The cutting and transferring of the cut implant to the delivery device may be a separate step performed by a separate tool or assembly. For example, the system may incorporate a first means for cutting a piece of material into a cut implant, a second means for transferring the cut implant into a delivery device, and a third means for deploying the cut implant from the delivery device into the eye. It should be appreciated that the cutting, transferring and deploying may be integrated into a single device, or one or more may be separate devices used in conjunction with each other to transform a piece of material into a cutting implant for deployment in the eye. In a preferred embodiment, the cutting and transferring of the cutting implant is integrated into the first device and the deployment of the cutting implant in the eye is in the second device.

As used herein, the term "patch of material (patch of material)" refers to a piece of biologically derived material that has a dimension along at least one dimension that is greater than the dimension of a stent cut from the patch of material and implanted within a subject. In some embodiments, the pieces of material may have a generally square shape, and the stent cut or trephine from the pieces of material may have a generally rectangular shape. For example, a patch of material may be about 7mm wide by 7mm long by 0.55mm thick, while a stent cut from a patch of material may be 0.3-1.0mm wide by 7mm long by 0.55mm thick. The dimensions of the pieces of material and the cut stent may vary. The pieces of material prior to cutting may be between about 5mm to about 10mm wide, between about 5mm to about 10mm long, and between about 0.25mm to about 2mm thick. The stent cut from the sheet of material may be between about 0.3mm up to about 2mm wide, preferably between 0.7mm and 1.0mm wide. The stent cut from the sheet of material may be between about 5mm to about 10mm long. The stent cut from the sheet of material may be between 0.25mm and about 2mm thick. The pieces of material and the cut stent may each have the same length and the same thickness, but the widths are different from each other. The pieces of material and the brackets cut from the pieces of material may also have different lengths and thicknesses. For example, a piece of material may have a first thickness and a stent cut from the piece of material has the same thickness, but may be folded or rolled to a different thickness than the piece of material when implanted. The cut stent need not be rectangular in shape and may have a non-rectangular shape, such as an angular wedge shape or any of a variety of shapes, to provide a particular clinical outcome. For example, a stent cut into a "dog bone" shape with enlarged distal and proximal ends may provide additional fixation within the target tissue. The stent may be cut to have a narrow elongate shape on the leading end and an enlarged dimension on the trailing end to provide ease of insertion and to provide at least one end for fixation.

In some embodiments, a patch of material may have a relatively large width (e.g., 10mm x10 mm), and the stent is cut from the patch into strips having a much smaller width (e.g., about 1.0mm to about 1.5 mm), and then the cut stent is compressed into a delivery catheter having an inner diameter of about 0.8mm, such that the width of the stent substantially fills the inner diameter. The stent may substantially fill the inner diameter of the delivery catheter even though the stent is not oversized relative to the catheter and thus remains uncompressed. The stent may be oversized relative to the internal dimensions of the catheter and compressed into the catheter to substantially fill it. Further, the size of the cut stent may vary depending on the size of the catheter through which the stent is to be deployed. For example, the inner diameter of the delivery catheter may be about 600 microns to about 800 microns. Thus, depending on whether the stent is to be compacted into a delivery tube and depending on the internal dimensions of the delivery tube, the stent may be cut or trephine to any of a variety of sizes.

The support cut from the sheet of material may have a width, a length and a thickness. In one embodiment, the width of a stent cut from a sheet of material using a cutting device described herein may be at least 100 microns up to about 1500 microns, or between 100 microns and 1200 microns, or between 100 microns and 900 microns, or between 300 microns and 600 microns. The stent cut from the sheet of material may have a width of at least about 100 microns and a width of no more than 1500 microns, 1400 microns, 1300 microns, 1200 microns, 1100 microns, 1000 microns, 900 microns, no more than 800 microns, no more than 700 microns, no more than 600 microns, no more than 500 microns, no more than 400 microns, no more than 300 microns, or no more than 200 microns. The length of the stent cut from the sheet of material may vary depending on the location of stent implantation. In some embodiments, the length of the stent is between 1mm and 10mm, or more preferably between 3mm and 8 mm. The thickness of the stent cut from the pieces of material may be 100 microns up to about 800 microns, or 150 microns up to about 600 microns. In one embodiment, the biomaterial forming the scaffold may have a thickness of not less than 100 microns and not more than 5mm. The thickness of the stent may also depend on whether the stent is folded or rolled up at the time of implantation, so that a sheet of material having a thickness of only 250 microns may be cut into the stent and the stent folded at the time of implantation to double the thickness to about 500 microns. The thickness of the scaffold may also depend on what bio-derived material is used. For example, scleral or corneal tissue may typically have a thickness of about 400 microns, but may shrink to about 250-300 microns after harvesting. Thus, a scaffold cut from a contracted corneal tissue piece may have a thickness of only 250 microns.

In some embodiments described in more detail below, stents cut from a sheet of material are cut to substantially fill a catheter through which they are advanced for delivery. In other embodiments, the stent may be cut into an implant that is oversized relative to the size of the catheter through which it is deployed. In this embodiment, the stent may be cut to have a first size that is oversized compared to the internal size of the delivery catheter. Oversized stents may be prepared within the delivery conduit, for example, by compaction or compression with a tool, such that the stent assumes a second, smaller size when prepared within the conduit. After deployment in the eye and release of the stent from the delivery catheter, the stent may achieve a third dimension that approximates its original first dimension. This will be described in more detail below.

In a non-limiting example, the biological tissue scaffold has a dimension of not less than 0.1mm and not more than 8mm and a thickness of not less than 50 microns and not more than 8mm in any direction. In a non-limiting example, the stent is about 6mm long, about 300-600mm wide, and about 150-600mm thick. The cut may be no less than 1mm and no more than 8mm in any direction. In one non-limiting example, the cut tissue has dimensions of 100-800 microns wide and 1mm-10mm long. It should be appreciated that multiple stents may be delivered to one or more target locations during an implantation procedure.

Figures 2 and 6 illustrate interrelated embodiments of a system 100 for preparing and delivering a biological intraocular stent to increase water outflow and reduce intraocular pressure. The system 100 can include a tissue cassette 200, the tissue cassette 200 having at least a portion configured to reversibly and operatively couple with the cutting device 300 and the delivery device 400. The cutting device 300 shown in fig. 2 and 6 includes an integrated loading feature configured to load a cut stent into the tissue cassette 200 after cutting the stent with the cutting device 300. The system 100 may also incorporate a cutting device 300 without an integrated loading feature (see fig. 18A-18E and 18F-18H). In this embodiment, the system 100 may include a separate loading device 600 configured to couple with the cartridge 200 to load the cut stent produced by the cutting device 300 (see fig. 19A-19B). Once cut using the cutting device 300, the stent may be manually transferred from the cutting device 300 to the loading device 600, for example, using forceps. The loading device 600 may be used to push a cut stent into the area of the tissue cassette 200 coupled to the loading device 600. The loaded tissue cassette 200 may then be detached from the loading device 600 and coupled to the delivery device 400 for delivery into the eye.

Each system 100 may be provided without a cutting device 300 and include only a tissue cassette 200 and a delivery device 400. In such an embodiment, tissue cassette 200 may include pre-cut scaffold 105 within cassette 200 ready to be engaged with delivery device 400 for deployment into the eye. The cartridge 200 with the pre-cut stent 105 may be immersed in a stable solution. Thus, where the system is described as including a cutting device 300, it should be appreciated that the cutting device 300 may not be used at the time of surgery, but rather the scaffold 105 is provided in a pre-cut and/or ready configuration within at least a portion of the delivery device 400 or tissue cassette 200.

Fig. 2 shows a first cartridge 200 shown separated from the cutting device 300 and another cartridge 200 mounted with a conveyor. The cassette 200 is configured to receive the pieces 101 of material within the cassette 200 and secure the pieces 101 of material in preparation for cutting by the cutting device 300. Cutting device 300, when operatively engaged with cartridge 200, is configured to form biological intraocular stent 105 from sheet 101 of material held within cartridge 200. The delivery device 400, when operatively engaged with the cassette 200, is configured to deliver the cut implant 105 from the cassette 200 to an implantation site. The tissue cassette 200 in the embodiment of fig. 2 is configured to mate with both the cutting device 300 and the delivery device 400 such that the entire tissue cassette 200 is removed from both devices 300, 400 of the system 100 and transferred between the two devices 300, 400.

Fig. 6 illustrates one interrelated embodiment of the system 100 and includes a tissue cassette 200 configured to be operatively coupled with a cutting device 300 and a delivery device 400. However, the entire tissue cassette 200 need not be completely removed from the cutting device 300 in order to be coupled with the delivery device 400. In this embodiment, the tissue cassette 200 may include a distal nose cone assembly 274 configured to be separated from the proximal portion 207 of the cassette 200 and coupled with the delivery device 400. The nose cone assembly 274 may include at least a portion of the distal portion 205, such as a nose cone 275 and a shaft 210 extending distally from the nose cone 275.

In still other embodiments, cassette 200 need not include portions configured to receive sheet 101 of material within cassette 200. For example, the cartridge 200 may include only a nose cone assembly 274 including a nose cone 275 having a distal shaft 210. The nose cone 275 with the distal shaft 210 may be coupled to a cutting device 300, the cutting device 300 configured to receive the pieces 101 of material in at least one region and secure the pieces 101 of material in preparation for cutting by the cutting device 300. The nose cone 275 and distal shaft 210 may be arranged relative to the cutting device 300 such that the cut stent may be transferred thereto for deployment into the eye. Fig. 14I schematically illustrates a nose cone assembly 274 coupled to a cutting assembly 500. The nose cone assembly 274 includes a nose cone 275 having a proximal end coupled to the cutting assembly 500 and a distal shaft 210 protruding from the nose cone 275 along a longitudinal axis a. The cutting assembly 500 may be part of a cutting device 300 as described herein.

The cartridge may comprise any of a variety of structural arrangements as described herein, but generally refers to a component that is transferable between two or more devices. The cassette is transferable between the cutting device and the conveyor. The cassette may be configured to hold a piece of material for cutting into stents and provide a conduit for deploying the stents into the eye. However, the cassette need not be configured to hold a sheet of material for cutting. The cartridge may include a shaft configured to receive the cut stent from the cutting assembly and then deploy the stent from the shaft into the eye. Any of a variety of configurations are described and contemplated herein.

Each of these systems and their respective components will be described in more detail herein.

Fig. 2 and also fig. 3A-3C illustrate one embodiment of a tissue cassette 200, the tissue cassette 200 configured to hold a patch of material for cutting and to provide a conduit for deploying a cut scaffold into an eye. The cartridge 200 may include a distal portion 205, the distal portion 205 coupled to a proximal portion 207 and extending distally from the proximal portion 207. The distal portion 205 may include an elongate member or shaft 210 having an inner catheter or lumen 238 sized to receive and deploy the stent 105. The proximal portion 207 may include a base 224 and a cover 214 movably attached to the base 224. The proximal portion 207 is intended to remain outside the eye, while the distal portion 205 is configured to be inserted into the eye to deploy the stent 105 within the target tissue. Implant 105 may be advanced from proximal portion 207 of cassette 200 into a deployment positioned within distal portion 205 of cassette 200. The distal portion 205 of the cartridge 200 is insertable into the anterior chamber of the eye so that it can be positioned adjacent to the ocular tissue in which the implant 105 is deployed from the cartridge 200. For example, the distal portion 205 of the cartridge 200 may be inserted into the anterior chamber through an intracorneal incision while the proximal portion 207 of the cartridge 200 remains outside of the eye (e.g., coupled to the delivery instrument 400).

Fig. 6 and also fig. 7A-7C illustrate another embodiment of a tissue cassette 200, the tissue cassette 200 configured to hold a patch of material for cutting and to provide a conduit for deploying a cut stent into an eye. Tissue cassette 200 may include a distal portion 205, with distal portion 205 coupled to a proximal portion 207 and extending distally from proximal portion 207, proximal portion 207 including a shaft 210, with shaft 210 having an inner catheter or lumen 238 (visible in fig. 14I) sized for receiving and deploying stent 105. The proximal portion 207 may also include a base 224 and a cover 214 movably attached to the base 224. Distal portion 205 and shaft 210 may be removably attached to proximal portion 207 of cartridge 200. For example, the proximal portion 207 may be retained within the cutting device 300, while the removable nose cone assembly 274 including the nose cone 275 and the shaft 210 may be separated from the proximal portion 207 and engaged with the delivery instrument 400 (see fig. 9A-9D).

It should be appreciated that the distal portion 205 of the cartridge 200 may be used for other delivery pathways (e.g., transscleral delivery). Deploying the implant 105 into ocular tissue may include the implant 105 being at least partially between the ciliary body and the sclera of the eye. Implant 105 may be positioned between the ciliary body and the sclera within the ciliary body separation split.

The shaft 210 (also referred to herein as an introduction tube, applicator, catheter, or delivery body) of the cartridge 200 that extends in a distal direction outwardly from the proximal portion 207 of the cartridge 200 includes at least a portion that extends along the longitudinal axis a. At least another portion of the shaft 210 may be angled, curved, or flexible such that it may form a distal bend or curve away from the longitudinal axis a. The distal region 212 of the shaft is a tangential arc of the proximal region of the shaft 210 having a radius of between 10-20mm, preferably about 10-15mm, or about 12mm. In some embodiments, the shaft 210 may include a flexible portion and a rigid portion such that the shape of the shaft is changed depending on the relative positions of the portions. Figures 3A-3C also illustrate embodiments of figures 7A-7C having a proximal portion extending along a longitudinal axis a and a distal region 212 that curves downwardly away from the longitudinal axis a. The distal region 212 may include an opening 230 from the lumen 238 through which opening 230 the stent 105 may be deployed. The opening 230 from the lumen 238 may be positioned in a plane perpendicular to the plane of the longitudinal axis a of the distal region 212 of the shaft 210. The opening 230 from the lumen 238 may be positioned in a plane that is angled relative to the longitudinal axis a of the distal region 212 of the shaft 210. The distal region 212 of the shaft 210 may be sloped such that the opening 230 into the lumen 238 is elongated rather than circular, and the distal-most tip 216 of the shaft 210 extends beyond the opening 230. The chamfer may be about 10-45 degrees, preferably about 12-16 degrees, or about 15 degrees. The distal-most end 216 of the shaft 210 may be a pointed end or a blunt end (which is square such that it does not form a tip). The shape of the opening 230 may be a function of the overall cross-section of the shaft 210 at the distal region 212 and the angle of the opening 230 relative to the longitudinal axis a of the distal region 212. For example, if the distal end region 212 of the shaft 210 has a rectangular cross-section and the opening 230 is cut perpendicularly relative to the longitudinal axis a, the cross-sectional shapes of the opening 230 and the shaft 210 substantially match. If the shaft 210 has a rectangular cross-section and the opening 230 is cut in a less than perpendicular manner relative to the longitudinal axis a, the opening 230 may have an elongated rectangular shape as compared to the rectangular shape of the shaft 210. The opening 230 may also have a first shape near the beveled heel and a second shape near the distal-most tip 216. For example, the opening 230 near the beveled heel may be rounded and the opening 230 near the distal-most tip 216 may be squared off. It should also be appreciated that the opening 230 need not be located at the distal-most end of the shaft 210. The opening 230 may be formed in a sidewall of the shaft 210 such that the stent 210 is pushed out of the lumen 238 in a direction that is angled relative to the longitudinal axis of the lumen 230. The opening 230 may be positioned in the shaft 210 relative to the cartridge 200 such that it is positioned at a front end, an underside, an upper side, and/or another side of the shaft 210. The distal region 212 of the shaft 210 may have a cross-sectional shape that is circular, oval, rounded rectangular, rounded square, diamond, teardrop, or other shape, and the distal-most tip 216 has a varying tip shape, including a blunt tip, bullet tip, scraper tip, or pointed tip. The distal region of the shaft 210 may have any of a variety of configurations known in the ophthalmic arts.

The shaft 210 may be used to create a ciliary separation gap in the upper ciliary body cavity. The distal end region of the shaft 210 may be shaped to form a split and provide a conduit for delivering material into the supraciliary cavity of the eye. The shaft 210 may also be used to deliver viscous materials, such as viscoelastic fluids, or non-viscous materials, such as scleral tissue, for example, using a pusher as a plunger. For example, the viscoelastic material may be delivered to the region of the eye through the shaft 210 before, during, and/or after stent implantation. A corneal incision may be made with a surgical knife or other tool, and the shaft 210 inserted through the incision and the distal end of the shaft 210 navigated to the desired location for delivery. The distal end of the shaft 210 may include a scraper that may be used to separate tissue layers and create a ciliary separation gap in the supraciliary cavity between the sclera and the ciliary body. The size, surface finish and shape of the distal end minimizes trauma. The shaft 210 may additionally include one or more indicia providing user information regarding the insertion distance. The distal region of the shaft 210 may include one or more markers for angular reference of how deep the tongue of the shaft 210 has been inserted into the upper ciliary body cavity. The one or more indicia may be embossed, etched, or other type of indicia and one or more fenestrations on the shaft 210, as will be described in more detail below. The length of the shaft 210 is sufficient to allow the device to be used from a temporal or superior position.

The shaft 210 of the cartridge 200 is sized and shaped for delivery through a clear intracorneal incision to allow the stent 105 to be passed out of the distal end of the shaft 210. In at least some embodiments, the distal region 212 of the shaft 210 is sized to extend through an incision that is approximately 1mm in length. In another embodiment, the distal region 212 of the shaft 210 is sized to extend through an incision that is no greater than about 2.5mm in length. In another embodiment, the distal region 212 of the shaft 210 is sized to extend through an incision that is between 1.5mm and 2.85mm in length. In some embodiments, the maximum outer diameter of the shaft 210 is no greater than 1.3mm. The distal-most tip 216 of the shaft 210 may be blunt or sharp. The blunt distal-most tip 216 of the shaft 210 allows dissection between ocular tissues without the need to penetrate or cut the tissue to position the stent 105. For example, the distal-most end 216 of the shaft 210 may be configured for blunt dissection between the ciliary body CB and the sclera S (e.g., the supraciliary cavity) while the scaffold 105 remains completely enclosed within the shaft 210 during blunt dissection. In an alternative embodiment, the distal-most tip 216 of the shaft 210 has a sharp cutting configuration for application and implantation into the subconjunctival space through scleral wall dissection. In yet another embodiment, the distal-most tip 216 may have a cutting configuration for dissection and implantation into schlemm's canal or transscleral implantation.

The shaft 210 may be a hypotube that is no greater than about 18G(0.050"OD,0.033"ID)、20G(0.036"OD,0.023"ID)、21G(0.032"OD,0.020"ID)、22G(0.028"OD,0.016"ID)、23G(0.025"OD,0.013"ID)、25G(0.020"OD,0.010"ID)、27G(0.016"OD,0.008"ID)、30G(0.012"OD,0.006"ID) or 32G (0.009 "od,0.004" id). In some embodiments, shaft 210 is a hypotube having an inner diameter of less than about 0.036 "to about 0.009" (0.230 mm-0.900 mm). The inner diameter of the shaft 210 may be about 0.600-0.900mm. The system may incorporate 600 micron shafts 210 or 800 micron shafts 210. Other dimensions of the shaft 210 are contemplated herein, depending on the particular patient condition and clinical needs.

In a preferred embodiment, the stent described herein may be formed as a solid strip of material without any lumens, but it should be understood that the stent may also include lumens. Thus, stents are generally not delivered over a guidewire as many conventional glaucoma shunts. Furthermore, the stents described herein may be formed from relatively soft tissue that is more brittle than typical shunts formed from more rigid polymeric or metallic materials. A rigid shunt may be implanted so that the distal end of the shunt is used to create a blunt dissection at the interface of the tissue through which the shunt is inserted. The stents described herein are preferably deployed using a retractable cannula-type syringe or introducer tube that, once in the proper anatomical position, can be retracted, thereby allowing for a more gentle externalization and precise positioning of the stent. The stents described herein may also be deployed by distally advancing a pusher to push the stent out of the introducer tube. The distal advancement of the pusher may be a slow incremental advancement under direct user control, depending on the degree of depression of the button or the degree of advancement of the slider. Distal advancement may be sufficient to deploy the stent from the lumen into the tissue. Where distal advancement is preferably controlled by the user in a slow, incremental manner, proximal retraction may be an all-or-nothing type (all-or-nothing sort) of actuation achieved by a spring-actuated mechanism. For example, if a user wishes to quickly remove the shaft of the device for any of a number of reasons other than deploying the stent, retraction may be relatively quick. Retraction need not result in deployment of the stent. For example, the pusher may be withdrawn proximally relative to the stent inside the shaft prior to proximal axial retraction. This may withdraw the shaft from the split, if desired, while the stent remains within the lumen.

The size of the shaft 210 may be selected based on the desired size of the stent to be implanted. The stent 105 may be sized to substantially fill the lumen 238 of the shaft 210 (or the lumen of at least a portion of the shaft 210 through which the stent is delivered) so that the stent may be pushed distally through that portion. In some embodiments, the stent that substantially fills the lumen is pushed distally without wrinkling or being damaged. In other embodiments, a stent that substantially fills the lumen is pushed distally through the shaft 210 as follows: the tissue is compacted into a plug having a more dense configuration than the scaffold when cut from the pieces. The dimensional difference or gap between the width and height dimensions of the stent 105 and the interior dimensions of the catheter may be up to about 200% of the dimensions of the stent 105. The maximum dimension of the catheter is related to the maximum dimension 105 of the stent. For example, if the stent width is about 1mm, the maximum dimension of the catheter may be 3mm, which results in a total gap between the stent width and the outer wall of the catheter of 200% of the stent width. The gap may be less than 5-10% of the maximum dimension of the bracket 105. In general, the smaller the gap between the stent 105 and the catheter, the better the result of advancing the stent 105 through the catheter. If the cross-sectional area of the shaft 210 is greater than 200% of the cross-sectional area of the cut stent 105, the stent 105 will bend as it is pushed through the shaft 210 for implantation into the eye. The cross-sectional area of the shaft 210 and the cross-sectional area of the bracket 105 preferably substantially match in size. The catheter may also be coated with a lubricious or low friction material (e.g., teflon) to improve advancement of the stent 105 through the catheter during deployment.

The cross-sectional area of the shaft 210 may also be smaller than the cross-sectional area of the bracket 105. As described above, the stent 105 may be cut to be oversized relative to the inner diameter of the shaft 210 such that the stent 105 is compressed, compacted, or otherwise minimally manipulated for delivery through a tube. The stent may be cut to have a first size that is oversized compared to the inner size of the shaft 210. Oversized stent may be prepared in the shaft, for example, by being compressed with a compression tool or push rod 420, such that stent 105 assumes a second, smaller size when prepared in the catheter. When the stent 105 is deployed in the eye and released from the shaft 210, the stent 105 may achieve a third dimension that approximates its original first dimension. The delivery and deployment will be described in more detail below.

The shaft 210 may, but need not be, entirely tubular, nor does the shaft 210 need to be circular in cross-section. For example, the cross-section of the shaft 210 may be circular, oval, square, rectangular, or other geometric shape. Furthermore, the entire length of the shaft 210 need not have the same cross-sectional shape or size. For example, the proximal end of the shaft 210 may have a first shape and the distal end of the shaft 210 may have a second shape. Fig. 5A-5B illustrate that the cross-section of the shaft 210 is rectangular. The lumen 238 of the shaft 210 need not be a completely closed channel. For example, the shaft 210 may incorporate one or more fenestrations, openings, segmented windows, or have one or more intermittent walls such that the lumen 238 through the shaft 210 is a partially enclosed passageway.

One or more discontinuities or fenestrations in the shaft 210 may be coated or covered with a material that allows visual inspection of the interior of the shaft 210. Fig. 16A-16C and 17A-17E illustrate an embodiment of a nose cone assembly 274 configured to reversibly couple with a delivery device. As discussed elsewhere herein, the delivery device 400 may include a proximal housing 405 (also referred to herein as a handle or handpiece) and at least one actuator 415. The delivery device 400 may also include a distal side connector 413b configured to be reversibly coupled to the nose cone assembly 274. The nose cone assembly 274 may include a nose cone 275 having a proximal region and a distal region. The coupler 413a may be positioned on a proximal region of the nose cone 275 configured to reversibly engage with a distal coupler 413b of the delivery device 400. The nose cone assembly 274 may further include a tubular shaft 210 protruding from a distal region of the nose cone 275. The tubular distal shaft 210 may incorporate one or more fenestrations 276 covered by a translucent or transparent material to reveal the lumen 238 of the tubular shaft 210. The one or more fenestrations 276 may form a metering system of the tubular shaft 210 configured to identify a depth of insertion of the tubular shaft 210 and/or a particular size (i.e., length) of an implant positioned within the lumen 238. The distal nose cone assembly 274 is shown in fig. 16A, and is also separated from the delivery device 400 in fig. 17B-17C, showing a proximal coupler 413a, which may be a bayonet connector on the proximal end region of the nose cone 275, configured to reversibly couple to the distal coupler of the delivery device 400. The distal shaft 210 protrudes from a distal region of the nose cone 275.

One or more fenestrations 276 may extend through the region of the distal shaft 210 that is covered by the transparent material. The fenestration 276 may be covered by reflow nylon (reflowed nylon) to form a continuous smooth channel that allows visualization of the interior of the shaft 210. The shaft 210 may include an introduction tube 277, the introduction tube 277 being at least partially enclosed by an outer tube member 278. The introduction tube 277 may be formed from a first material and the outer tube member 278 may be formed from a second, different material. The first material may be stainless steel or nitinol and the second material may be a polymer, such as nylon. The first material may be an opaque material and the second material may be relatively translucent or transparent. The introduction tube 277 may incorporate one or more fenestrations 276 through its side walls, the one or more fenestrations 276 being covered by an outer tube member 278 in a manner that allows a user to see through the outer tube member 278 and through the introduction tube 277 to visually inspect the lumen 238 of the introduction tube 277. Fenestration 276 allows a user to see that the implant is advancing through the guide tube 277 when the plunger is actuated through the guide tube 277. The fenestration 276 may also allow a user to evaluate the implant, such as the length of the implant, prior to deployment. The fenestration 276 may be of a known size or extend a known distance along the introduction tube 277 such that a user may assess the length of the implant within the lumen 238 by comparing the size of the implant within the lumen 238 relative to the known size of the fenestration(s) 276. Thus, the fenestration may form a metering system on the distal shaft that may be used to know the depth of insertion and/or the length of the implant within the lumen. Each fenestration 276 may be about 2mm-6mm long. The length of the proximal portion of the shaft 210 incorporating the fenestration 276(s) may be between about 4mm to about 8 mm. The fenestration 276 may extend through the sidewall on either side of the shaft 210 so that a user may inspect the lumen 238 from different orientations. The shape and size of the fenestration 276 may vary. In some embodiments, the fenestrations 276 are rectangular as shown in fig. 16A, but they may be any of a variety of geometric shapes. The material of the outer tube member 278 may fill the fenestration 276 of the introduction tube 277 to maintain a smooth and continuous tubular inner diameter. This prevents the implant within lumen 238 of introduction tube 277 from becoming stuck or from being prevented from sliding through lumen 238 toward distal region 212 of shaft 210.

Referring again to fig. 16A-16C, the shaft 210 may include a proximal portion extending along the longitudinal axis a and a distal region 212 distal of the fenestration 276 that is curved or flexed away from the longitudinal axis a. The distal region 212 of the shaft is a tangential arc of the proximal region of the shaft 210 having a radius of between 10-20mm, preferably about 10-15mm, preferably about 12mm. The curved distal region 212 may be incorporated into the shaft 210 with or without fenestration 276. The fenestration 276 may be positioned along a substantially straight proximal portion of the shaft 210 proximate to the bend or curve. The distal region 212 of the shaft 210 may be translucent or transparent and/or incorporate other windows into the lumen 238 of the shaft 210. In one embodiment, the introduction tube 277 terminates distally of the bend or curve of the shaft 210, and the outer tube member 278 extends beyond the terminal end of the introduction tube 277 (see fig. 16C). Thus, the distal end region 212 of the shaft 210 may be formed solely of the outer tube member 278. As discussed above, the outer tube member 278 may be a transparent or translucent material, such as nylon or other polymeric material that allows visual inspection of the shaft lumen 238. The transparent distal region 212 may be similarly smooth so as to maintain a smooth transition from the metal lead-in tube 277 to the polymer distal tip. The smooth transition prevents the implant within the lumen 238 from becoming misaligned or stuck during deployment. The distal region 212 may be bent downward from the proximal portion of the shaft 210 such that the distal opening 230 from the shaft 210 surrounds a different longitudinal axis a' than the proximal opening 280 of the access shaft 210, which may surround the first longitudinal axis a. The transparent distal region 212 may have a length of between about 5mm or about 3mm to about 7 mm. Distal opening 230 from lumen 238 may be angled to increase the size of opening 230, which may be about 1.5mm to about 2mm. The slope of distal region 212 may be between 10-45 degrees, preferably about 12-16 degrees. The distal-most end 216 of the shaft 210 may form a flat surface having a thickness of about 0.10mm-0.20mm, preferably about 0.15 mm. Typically, the distal-most end 216 of the shaft 210 is not designed to cut or form perforations in ocular tissue, but rather is used for blunt dissection or separation between tissues. The distal end region 212 of the shaft 210 preferably does not contain sharp edges.

As described elsewhere herein, the shaft 210 may include an inner pusher or pushrod 420 (see fig. 12C-12D and 17E-17I). The push rod 420 may be formed of nitinol, stainless steel, or a monofilament or braided member. The push rod 420 may be a completely cylindrical element without a lumen that extends through the lumen 238 of the shaft 210 to engage against the proximal end of the stent 105. The push rod 420 is flexible enough to translate through the lumen 238 of the shaft 210 about a curvature near the distal region, and is also stiff enough to bear against the cut stent 105 within the lumen 238 to cause the stent 105 to be deployed in the eye. The push rod 420 may have an outer diameter differential along its length to increase its flexibility relative to the shaft 210, particularly if the shaft 210 has a curved distal region 212. As described above, the shaft 210 may be curved near the distal region to form a tangential arc having a radius of between 10-20mm, or preferably about 12 mm. The geometry of the push rod 420 may be varied over its length to provide improved flexibility to accommodate bending. In one embodiment, the push rod 420 may undergo a change in outer diameter between the proximal and distal ends (see fig. 17F). The distal region 440 of the push rod 420 may have a maximum outer diameter that is greater than the outer diameter of the intermediate region 442 of the push rod 420. The smaller outer diameter of the intermediate region 442 of the push rod 420 is designed to guide the curvature of the distal region 212 of the outer shaft 210. The push rod 420 may be tapered between sections such that the outer diameter of each region gradually varies toward a different outer diameter of an adjacent region. The larger outer diameter of the distal region 440 of the push rod 420 allows for a larger surface area to abut the cut stent within the lumen 238. If the outer diameter of the distal tip 441 of the push rod 420 is too small, the distal tip 441 will likely puncture the stent 105 rather than providing a bearing surface against the stent 105. The outer diameter of the distal region 440 may be about 0.525mm-0.575mm and the outer diameter of the intermediate region 442 may be narrowed to about 0.200mm-0.300mm. The outer diameters of the distal and proximal regions may be the same. The length of the intermediate region 442 may vary, but may be about 8mm-10mm. Typically, the length of the intermediate region 442 is longer than the length of the distal region 440. Distal region 440 may be about 2mm-5mm. The proximal region 444 of the push rod 420, which is configured to remain within the straight portion of the shaft 210, may be stiffer than the intermediate region 442 and is designed to couple to the actuator 415 on the housing 405 of the delivery device 400. Fig. 17G shows proximal region 444 of push rod 420 coupled to actuator 415a of housing 405.

The cassette may, but need not, be configured to hold the pieces 101 of material prior to cutting with the cutting device 300. A sheet 101 of material may be held in the region of the cutting device. Referring again to fig. 3A-3C and also to fig. 7A-7C, the proximal portion 207 of the cartridge 200 can include a base 224. The distal end region of the base 224 may be coupled to the shaft 210. The proximal region of the base 224 may include a recess 221, the recess 221 configured to receive the sheet 101 of material. The recess 221 may include an inverted V-shaped protrusion 271, which protrusion 271 may protrude upward from the centerline of the recess 221, pushing upward on the centerline of the piece of material 101 while allowing the sides of the piece of material 101 to hang down into the corresponding channels 270 on either side of the centerline. Fig. 7A-7C illustrate that the proximal portion 207 of the cartridge 200 may be reversibly coupled to a nose cone assembly that includes a shaft 210 and a nose cone 274.

The base 224 is configured to mate with the cover 214 and at least partially enclose the recess 221 of the sheet 101 of material. Cover 214 is configured to engage at least some portion of sheet 101 of material to stabilize tissue prior to and during cutting of sheet 101, for example, with cutting device 300. In one embodiment, the base 224 may include a slot 215 in an upper surface of the base 225, the slot 215 being sized and shaped to receive the cover 214. The cover 214 slides through the slot 215 until the lower surface of the cover 214 abuts the receiving surface 218 of the base 224. The contact between the lower surface of the cover 214 and the receiving surface 218 of the base 224 ensures that the centre line of the piece 101 of material within the recess 221 is in contact with the lower surface of the cover 214 at the projection 271 (see fig. 3C).

The cover 214 is shown in fig. 3A-3C as a fully removable element from the base 224. The cover 214 and the base 224 may optionally be coupled together by a hinge or other mechanical feature. For example, the cover 214 may rotate about the pivot axis of the hinge and remain connected to the base 224 even when in the configuration of the reveal recess 221. Fig. 7A-7C illustrate that the lid 214 may be switched between open and closed configurations by applying downward pressure at the front end of the lid 214 (fig. 7A) to open the lid 214 and applying downward pressure at the rear end of the lid 214 to close the lid 214 (fig. 7C). For example, the cover 214 may be lifted into an open configuration, revealing a recess 221 of the base 224, and the sheet 101 of material may be positioned within the recess 221. When the cover 214 is positioned back to the closed configuration, the panel 101 may be compressed and/or tensioned between the cover 214 and the base 224. Once the lid is in the closed configuration, the cartridge 200 may be inserted into the receptacle 306 of the cutting device 300 (see fig. 8).

Cover 214 (or some other element) may be configured to additionally exert an amount of tension on at least a portion of sheet 101 of material, such as stretching outward from the centerline of sheet 101 of material before cutting occurs, as described in U.S. patent No.10,695,218 issued 6/30/2020, which is incorporated herein by reference in its entirety.

A sheet 101 of material may be inserted into cassette 200 by a user at the time of surgery. The sheet 101 of material may be provided in a size that approximates the size of the recess 221 in the base 224. The user may trim the piece 101 of material before it is installed in the recess 221. Alternatively, the cartridge 200 may be provided in a form of a sheet 101 preloaded with material located in the recess.

As mentioned elsewhere herein, the cassette need not be configured to hold a sheet 101 of material for cutting by the cutting device 300. Instead, the cutting device 300 may be configured to hold the sheet 101 of material for cutting and then transfer the cut stent into a cassette coupled to the cutting device 300. Fig. 10A-10C and also fig. 16A, 17B-17C illustrate one embodiment of a cartridge 200, the cartridge 200 forming a nose cone 274 having a shaft 210 into which a cut stent may be loaded prior to insertion into the eye. The nose cone 274 may be reversibly coupled to the cutting device 300 with an integrated loading feature, or may be reversibly coupled to the loading device 600, the loading device 600 being configured to load the shaft 210 with a cut stent. Once loaded with the cut stent, the cartridge 200 may be removed from the cutting device 300 or the loading device 600 so that it may be coupled with the transfer device 400. The cassette 200 may be positioned relative to the cutting device 300, the cutting device 300 being configured to hold and cut the pieces 101 of material into the holders 105. Alternatively, the cartridge 200 may be positioned relative to a loading device configured to receive a cut stent and load the stent into the shaft 210. The coupling between the cutting device 300 (or loading device) and the cartridge 200 may align the longitudinal axis of the distal shaft 210 relative to the region of the device so that the cut stent 105 may be transferred into the distal shaft 210, for example, with a rod or other tool, as will be described in more detail below. The cartridge 200 with the distal shaft 210 of the stent 105 located inside thereof may then be separated from the cutting device 300 or the loading device 600 and transferred to a portion of the delivery device 400. Thus, the cartridge 200 need not include portions configured to hold the sheet 101 of material for cutting, but rather include transferable portions that can alternately couple with regions of the cutting device 300 or the loading device 600 and regions of the transfer device 400. In the case of reference to a cutting device 300 having an integrated loading feature, the cutting device 300 need not incorporate the loading feature. Instead, a separate loading device 600 may be used that is configured to couple with the cartridge 200 to transfer the cut stent into the cartridge 200 prior to coupling the cartridge 200 with the conveyor 400. Each of these embodiments will be described in more detail below.

Fig. 4A-4J also fig. 8 show an embodiment of a cutting device 300, the cutting device 300 having a cutting assembly for cutting a stent from a sheet 101 of material. Fig. 14A-14H illustrate various embodiments of a cutting assembly 500 that may be incorporated into the cutting device 300. The cutting device 300 is configured to cut or otherwise prepare the bio-derived tissue of the sheet 101 of material having a first profile or shape (e.g., a wider square sheet or sheet of material) to conform to a second profile or shape (e.g., a narrower rectangular strip of material) of the implantable stent 105 having the dimensions described herein. The cutting performed using the cutting device 300 described herein may involve a guillotine, ram, rotary, sliding, rolling, or pivoting blade cutting motion. In some embodiments, the cutting is performed normal to the plane of the piece of material. In some embodiments, cutting is performed axially along the catheter of the implant such that the cutting axis may be aligned, within or parallel to the implant catheter to allow unobstructed tissue loading and transfer for implantation without manipulation, tearing or damaging the fragile stent tissue.

As described above, the cutting process is preceded by a tissue fixation step in which the biologically derived tissue forming the scaffold is firmly fixed between two juxtaposed planar surfaces to ensure that the tissue is not wrinkled or misshapen and that the subsequent cuts are of accurate size. Fixation may optionally provide compression and tensioning or stretching of the tissue in at least one plane to ensure clean cutting of the tissue. Cutting assembly 500 may hold sheet 101 of material prior to cutting, or sheet 101 of material may be held within the area of tissue cassette 200 prior to being cut by cutting assembly 500. In some embodiments, the cutting device 300 in combination with the cover 214 of the cassette 200 may incorporate front-to-back capture such that the material 101 to be cut remains fixed in the z-plane, preventing movement until the tissue engages the cutting member 312.

The cutting may be performed within a path or conduit formed within the cassette 200. Thus, the implant 105 cut from the sheet 101 of material may be positioned within the catheter for delivery simultaneously or subsequently, or the implant 105 aligned with the catheter for delivery, such that the cut implant 105 may be delivered to the eye through the catheter without the need for the cut implant 105 to be transferred from the cassette 200.

As an example, the piece 101 of material held within the recess 221 of the cartridge 200 is cut by the cutting member 312 of the cutting device 300, forming a cut stent 105 within the recess 221 of the cartridge that can be pushed distally from the recess 221 into the lumen 238 of the shaft 210 of the cartridge 200, so that it can be deployed into the eye without completely removing the cut stent 105 from the cartridge 200 or at least the distal portion 205 of the cartridge 200.

Referring to fig. 4A-4B and also to fig. 6, the cutting device 300 may include a base 302 having a distal portion 305 and a proximal portion 307. The distal portion 305 may include a distal opening or receptacle 306 sized and shaped to receive the proximal portion 207 of the cartridge 200. The inner diameter of the receptacle 306 may be sufficient to receive the outer dimensions of the proximal portion 207 such that the proximal portion 207 may be inserted a distance into the receptacle 306. The cover 214 of the cassette 200 is positioned within the slot 215 to retain the sheet 101 of material within the recess 221. The upper surface of the cover 214 may extend above the upper surface of the base 224 such that the outer dimension of the proximal portion 207 is keyed. In other words, the external dimensions of the cartridge 200 are keyed and can only be inserted into the receptacle 306 of the cutting device 300 in a single orientation (e.g., the cap 214 on the upper side).

The cutting device 300 may additionally include a cutting assembly 500, the cutting assembly 500 having a cutting member 312, the cutting member 312 configured to cut the sheet 101 of material within the recess 221 of the cartridge into the support 105 (see fig. 4C). The configuration of the cutting member 312 may vary. In this configuration, the cutting member 312 may include at least a first blade 344a and a second blade 344b spaced apart from the first blade 344 a. The first and second blades 344a, 344b may be positioned above the sheet 101 of material when the cartridge 200 is mounted within the receptacle 306 of the cutting device 300. Actuation of the cutting member 312 causes the first and second blades 344a, 344b to be pushed toward the sheet 101 of material cut through the thickness, thereby forming the bracket 105. The blades 344a, 344b may have a width along the longitudinal axis a of the cartridge 200 that is sufficient to cut the full length of the sheet 101 of material. The distance between the blades 344a, 344b may be designed to achieve a desired width of the cut stent 105. The blades 344a, 344b may be positioned parallel to each other or may be angled. The blades 344a, 344b may be angled with respect to each other and/or with respect to the tissue to be cut. Angling the blades improves reproducibility of tissue cutting such that a very straight piece of tissue is formed from the piece 101 without any ridges along the sides of the newly cut scaffold. The angulation of the blades will be described in more detail below. The cutting member 312 may also include only a single blade 344, the single blade 344 configured to trim the stent from the piece 101 of material to size. Alternatively, the recess 221 of the sheet 101 for receiving material prior to cutting need not be located within the cassette 200, but may be located within the area of the cutting device 300, as will be described in more detail herein.

In some embodiments, blades 344a, 344b may be positioned above a piece 101 of material to be cut, and corresponding lower blades 345a, 345b may be positioned below the piece 101 of material. Thus, as blades 344a, 344b are pushed downward toward sheet 101 of material, they push sheet 101 of material toward lower blades 345a, 345b, such that the corresponding upper and lower blades cut completely through material 101 in two positions, thereby creating cradle 105.

The cutting member 312 may be actuated by a user to move the blade. The cutting device 300 may include one or more handles 343, the handles 343 being movably coupled to the base 302 to actuate the cutting member 312. The handle(s) 343 may be connected by a hinge 317 such that the handle 343 rotates relative to the base 302 about the pivot axis P of the hinge 317. For example, the handle 343 can be lifted to pivot into an open configuration as shown in fig. 4A and rotate about the pivot axis P back to a cut configuration as shown in fig. 4B.

When the handle 343 is lifted to the open configuration and the cutting member 312 is positioned away from the cutting configuration, the cartridge 200 can be inserted into the receptacle 306 of the cutting device 300. As best shown in fig. 4D-4E, cartridge 200 may be slid into receptacle 306 to position recess 221 of sheet 101 of retention material below upper blades 344a, 344b and above lower blades 345a, 345 b. The cover 214 holding the sheet 101 of material within the recess 221 may include an upper portion 220, the upper portion 220 tapering to a narrower lower portion 222. The lower portion 222 of the cover 214 is aligned with the protrusion 271 of the recess 221 and retains the piece of material 101 therebetween. The upper portion 220 of the cover 214 may slide over the upper blades 344a, 344b when the cartridge 200 is mounted with the cutting device 300. The lower portion 222 of the cover 214 is sized to slide between the upper blades 344a, 344b when the cartridge 200 is inserted into the receptacle 306 of the cutting device 300. Fig. 4D shows the upper blades 344a, 344b spaced apart from the lower blades 345a, 345b with the narrowed lower portion 222 of the cover 214 therebetween. Fig. 4E shows the handle 343 rotated back down to the cutting configuration and the upper blades 344a, 344b are pushed down towards the sheet 101 of material and towards the lower blades 345a, 345. Pieces 101 of material are cut by respective upper and lower blades to form brackets 105. The distance between the upper and lower blades determines the width of the support 105 cut from the sheet 101 of material.

The handle 343 can be opened in any of a number of orientations relative to the base 302. For example, the pivot axis P of the hinge 317 may be substantially orthogonal to the longitudinal axis of the base a. In this embodiment, the hinge 317 may be positioned on the distal end of the base 302 such that the handle 343 articulates open by rotating upward and toward the distal end of the base 302. The upper blades 344a, 344b may be spring loaded such that they tend to return to the open configuration as the handle 343 is lifted or released.

Once cut, the stent 105 may be received by the cartridge 200 and cutting member 312 on all sides, thereby forming a complete enclosure or stent cutting chamber for the stent 105 within the assembly of the cutting device 300 and cartridge 200. For example, the bottom and top of the rack cutting chamber may be formed by the lower portion 222 of the cover 214 and the protrusions 271 of the recess 221. The walls of the stent cutting chamber may be formed by the upper blades 344a, 344b and lower blades 45a, 345b of the cutting member 312. Together, the walls of the stent cutting chamber may be rectangular to help constrain and guide the pusher 320 of the cutting device 300, the pusher 320 being advanced to push the stent 105 distally from the stent cutting chamber into the lumen 238 of the shaft 210. In one embodiment, the cross-section of the stent cutting chamber may be at least partially arcuate or circular. The upper and lower surfaces of the cutting chamber may be curved or non-planar. As an example, the lower portion 222 of the cover 214 may be concave, forming a concave surface (concavity), forming an arched top of the cutting chamber. The bottom of the cutting chamber formed by the protrusions 271 may incorporate corresponding concavities. The arched top and concave bottom of the cutting chamber reduce the amount of open space created around the cut stent 105 relative to the inner wall of the shaft that might otherwise cause the pushrod to deviate from the track or allow the cut stent 105 to deviate from the desired path during deployment. Minimizing space within the shaft relative to trephine holder 105 improves advancement of holder 105 through the device. The cut stent 105 may in turn have a cross-sectional shape that more closely matches the cross-sectional shape of the delivery catheter through which the stent 105 must be advanced. The corresponding shape eliminates the excess space of the upper and lower sides of the cut stent 105 relative to the catheter. This in turn provides a better guide for the pusher 320 to advance the cut stent 105 toward the distal end of the shaft. The stent 105 may also be cut oversized relative to the catheter, as discussed elsewhere herein, and compressed, compacted, or otherwise manipulated within the catheter prior to deployment.

Once cut, the stent 105 may be axially aligned with the lumen 238 of the shaft 210 of the cartridge 200. Fig. 4F-4G and also fig. 4H-4J illustrate that the cutting device 300 may include a pusher 320, the pusher 320 configured to slide distally relative to the base 302 into the proximal region of the cartridge 200 to advance the cut stent 105 from the fully enclosed position along the implantation catheter into the lumen 238 of the shaft 210. The pusher 320 is not visible in the embodiment of fig. 6. However, the base 302 may include an actuator 304, such as a dial, button, slider, or other input, operatively coupled to a proximal end region of the pusher 320 that, upon actuation, moves the pusher 320 distally relative to the base 302. Any of the various user actuators 304 are considered herein to move the pusher 320 to seat the stent 105 relative to the lumen 238. This ready step with respect to the pusher 320 of the cutting device 300 ensures that after removal of the cartridge 200 from the cutting device 300 and before coupling of the cartridge 200 with the conveyor 400, the cut stent 105 is maintained in a completely enclosed space on all sides (i.e. the area of the shaft 210).

Fig. 4H shows that the pusher 320 of the cutting device 300 can be advanced distally through the base 302 as the handle 343 is pushed down toward the base 302 (e.g., the blade 344 is positioned in a cutting configuration relative to the implant 105). Fig. 4I shows the pusher 320 ready to engage the stent 105 in the recess 221 on the proximal end. Fig. 4J shows pusher 320 having pushed stent 105 distally into lumen 238 of shaft 210 of cartridge 200. As described above, the blades 344, except for the upper cover 214 and the lower protrusions 271, create a complete enclosure of the stent 105 for cutting on all sides, preventing the stent 105 from bending within the lumen 238 during this distal advancement into the lumen 238. The catheter in which the stent 105 is held matches (or undersized by) the outer dimensional dimensions of the stent being implanted, thereby preventing buckling and wrinkling as the stent 105 is pushed into the ready position.

The holder 105 may be pushed into the distal end region 212 of the shaft 210 and the cartridge 200 removed from the cutting device 300. Once the cutting device 300 and the cartridge 200 are separated from each other, the cartridge 200 is ready to be loaded with the delivery device 400 for insertion of the stent 105 into the eye.

The pieces 101 of material may be cut and loaded into the shaft 210 of the cartridge 200 in a variety of ways. As discussed elsewhere, a sheet 101 of material may be cut to substantially the same dimensions as the conduit through which the sheet 101 of material is to be conveyed. The piece of material 101 may preferably be cut slightly larger than the size of the catheter through which the piece of material is to be delivered so that the stent 105 is compressed and packaged within the catheter so that it may be more easily advanced through the lumen 238. The cutting may be performed as described above with respect to fig. 4A-4E. Other cutting assemblies 500, as described below and with respect to fig. 14A-14H, may also be used to perform cutting and transferring pieces of material into the shaft 210. The cutting assembly 500 described herein may form part of a tissue cassette 200, a cutting device 300, or a delivery device 400. Preferably, the cutting assembly 500 is part of the cutting device 300. The cutting device 300 may be coupled to at least a portion of the cartridge 200, such as a nose cone assembly 274, with the distal shaft 210 extending from the nose cone 275, such that the cut stent 105 may be prepared within the shaft 210 for delivery using the delivery device 400. The cartridge 200 may include a proximal portion 207 configured to hold a piece of material for cutting, as shown in fig. 2, 3A-3C, or 7A-7C, or a removable nose cone 274 and shaft 210, as shown in fig. 9A-9D, 10A, that does not include a proximal portion 207 for holding a piece of material. The loading of the stent 105 need not be performed by the cutting device 300 nor does the cutting device 300 need to engage with the cassette 200 to load the cut stent into the cassette. The cut stent 105 may be manually transferred from the cutting device 300 into a separate loading device 600 configured to engage the cartridge 200 and load the cut stent 105 into the cartridge. Cassette 200, whether configured to hold a piece of material for cutting or not, may be a transferable component designed to couple with a cutting assembly, prepare with a cut stent, remove from the cutting assembly, and couple with a delivery device to deploy the cut stent into an eye.

Fig. 14A illustrates one embodiment of a cutting assembly 500. The cutting assembly may be part of a cutting device 300 configured to engage with the cartridge. Cutting assembly 500 may also be a separate component of a tissue preparation system configured to hold sheet 101 of material and cut sheet 101 of material, but not configured to load a cut scaffold into a delivery shaft. The cutting assembly 500 may cut a sheet 101 of material that may be held within a cassette or within the area of the cutting assembly 500. The cut stent may be transferred from the cutting assembly 500 into the distal shaft 210 of the cartridge 200 for delivery through the shaft into the eye. The cut stent may be manually transferred from the cutting assembly 500, for example, with forceps, into a loading system configured to load the cut stent into the distal shaft 210. The cutting assembly 500 may incorporate a cutting die 511 positioned relative to a slot 507 in a base 509 and a movable member 505 having a planar bearing surface 513 coupled to the base 509. The movable member 505 may be rotated 90 degrees relative to the base 509 from a first position to a second position. When the movable member 505 is rotated to its second position, the sheet 101 of material may be placed against the bearing surface 513. Cutting die 511 may press sheet 101 of material against bearing surface 513. Pushing cutting die 511 toward bearing surface 513 may cut through sheet 101 of material in two locations (e.g., in one or two locations, as described elsewhere herein). Excess tissue may be removed from bearing surface 513 and movable member 505, which still holds cut stent 105 on its bearing surface 513, is rotated toward the first position. This places the cut stent 105 on the bearing surface 513 within the path of the slot 507 so that a compression tool 517 or other member may load the cut stent 105 into the slot 507. The slot 507 may have a terminal region 508, which terminal region 508 is aligned with the longitudinal axis a of the distal shaft 210 when the cartridge 200 is coupled to the cutting device 300. The cut stent 105 may be pushed by the compression tool 517 at an angle to the longitudinal axis of the shaft 210 (e.g., orthogonal to the longitudinal axis of the shaft 210). The terminal region 508 may have a circular cross-sectional shape similar to the cross-sectional shape of the distal shaft 210. The cut stent 105 positioned within the terminal region 508 may then be pushed into the lumen of the distal shaft 210 so that it is ready for delivery. The dimensions of the slot 507 and/or the termination area 508 may be smaller than the dimensions of the cut stent 105 such that advancement of the compression tool 517 into the slot 507 causes the stent 105 to be compressed and compressed into a plug. Once the cut stent 105 is positioned within the distal shaft 210 of the cartridge 200, the cartridge 200 may be removed from the cutting device 300 and transferred to the delivery device 400 for deployment into the eye. The cutting, transferring, loading and preparation may be combined into a single assembly or into separate components configured to cooperate with each other.

Fig. 14B illustrates one embodiment of a correlation of a cutting assembly 500 for cutting a sheet 101 of material and translating the cut stent 105 for delivery. As with the embodiment of fig. 14A, the cutting assembly 500 may be part of a cutting device 300, the cutting device 300 being configured to engage with a cartridge. The pieces of material may be held within the region of the cassette for cutting or may be held by a portion of the cutting assembly 500. Cutting die 511 may be inserted through movable element 515 (referred to herein as a gate, pad, or other component) to cut pieces 101 of material. Pad 515 may be configured to hold tissue thereunder, apply pressure to tissue thereunder, and/or compress tissue thereunder. A sheet 101 of material may be positioned against the bearing surface 513. The bearing surface 513 need not be part of the movable member as in the previous embodiments, but may be at least part of the base 509. The sheet 101 of material may be compressed between the bearing surface 513 of the base 509 and the pad 515. Cutting die 511 may be advanced through pad 515 such that blade(s) of cutting die 511 cut through sheet 101 of material. If cutting die 511 has two blades (e.g., two blades as shown in FIGS. 14A-14B, 14E, 14F-1 and FIGS. 18E-18G, 22A and 23C), cutting die 511 cuts through sheet 101 at two locations. If cutting die 511 has a single blade, cutting die 511 cuts through sheet 101 at a single location. In the case of two blades, the blades may be positioned parallel to each other or may be angled. Angling the blades improves reproducibility of tissue cutting such that a very straight piece of tissue is formed from the piece 101 without any ridges along the sides of the newly cut scaffold. The angulation of the blades will be described in more detail below.

After the piece 101 of material is cut, excess tissue may be removed and the pressure applied by pad 515 released. The cutting die 511 may include a spring 516 to return it to its original position and the pad 515 and cutting die 511 no longer apply pressure to the cut stent 105. The cut stent 105 may be positioned relative to the slot 507 in the base 509 such that the compression tool 517 may push the cut stent 105 through the slot 507 toward the termination area 508. The positioning of the holder 105 may be performed manually by a user, for example using forceps or using a tool as part of the cutting/loading system. Fig. 14B shows loading the cut stent 105 into a catheter from the side of the shaft 210 or orthogonal to the axis of the shaft 210. As discussed elsewhere, the cut stent 105 may be oversized relative to the size of the slot 507 such that pushing the stent into the catheter compresses and compacts the stent 105 for delivery. The slot 507 may have a terminal region 508, which terminal region 508 is aligned with the longitudinal axis a of the distal shaft 210 when the cartridge is coupled to the cutting device 300. The cut stent 105 positioned within the terminal region 508 may then be pushed into the distal shaft 210 so that it is ready for delivery. The cut stent 105 may be positioned within the terminal region 508 by pushing the stent in a first direction (e.g., transverse to the longitudinal axis of the shaft 210), and then the cut stent 105 may be positioned within the distal shaft by pushing the cut stent 105 in a second direction (e.g., along the longitudinal axis of the shaft 210). The cassette, now containing the cut stent 105, may be removed from the cutting device 300 and transferred to the delivery device 400 for deployment into the eye.

Fig. 14C shows an interrelated embodiment of a cutting assembly 500, the cutting assembly 500 being used to cut a sheet 101 of material and to translate the cut stent 105 for delivery. The cutting assembly 500 may additionally incorporate a movable stop 520, the stop 520 being positioned between the sheet 101 of material and the slot 507 through which the cut stent 105 is to be advanced. Pad 515 and cutting die 511 may press sheet 101 of material against bearing surface 513 of base 509. The sheet 101 of material may be enclosed between the bearing surface 513 on the underside, the movable stop 520 on the distal side, and the pad 515 on the upper side. The cutting die 511 may include a single blade (or two blades) and be advanced through the compressed piece of material 101 to cut the piece at a single location to create the stent 105. The cutting die 511, pad 515, and movable stop 520 may be withdrawn away from the cut stent 105 so that the compression tool 517 may push the cut stent 105 distally into the slot 507 for delivery. When the cartridge is coupled to the cutting device 300, the terminal end region 508 of the slot 507 may be aligned with the longitudinal axis a of the distal shaft 210. The cut stent 105 located within the terminal region 508 may then be pushed into the distal shaft 210 so that it is ready for delivery as described elsewhere. Fig. 14I shows the nose cone assembly 274 arranged relative to the cutting assembly 500 of fig. 14C. The longitudinal axis a of the distal shaft 210 of the nose cone assembly 274 may be aligned with the terminal end region 508 of the slot 507 such that the compression tool 517 may push the cut stent 105 into the shaft 210. Once the cut stent 105 is compressed into the lumen 238 of the shaft 210, the nose cone assembly 274 may be removed from its association with the cutting assembly 500 and transferred to the delivery device 400 for deployment into the eye.

The position of the movable stop 520 relative to the cutting blade of the die 511 can be adjusted to achieve different holder widths. For example, the movable stopper 520 may be moved toward a single blade of the cutting die 511 to reduce the width of the bracket, and may be moved away from the cutting die 511 to increase the width of the bracket. The position of the movable stop 520 relative to the cutting die 511 may be selected by a user, for example, by a dial or other user interface that allows for incremental adjustment. The turntable may range between about 0.6mm and about 1.9mm and may include markings arranged in 1/4 to 1/16 threads. As described elsewhere herein, the cutting die 511 of the cutting assembly 500 may be attached to a rod, handle, or other actuator 343 to advance a single blade through the sheet 101 of material held against the bearing surface 513 by the pad 515 when the width is selected. In one embodiment, the bearing surface 513 may be a soft plastic material (e.g., 1/16 "90A silicone).

Fig. 15A-15B illustrate a trephine or cutting device 300 having a cutting assembly 500. The cutting device 300 may include a handle or actuator 543 movably coupled to the base 509 to actuate the cutting assembly 500. For example, the actuator 543 is configured to raise and lower the cutting die 511 relative to the bearing surface 513 of the base 509. The configuration of the actuator 543 may vary as described herein, including a lever or scissor handle (scissoring handles).

In other embodiments, the actuator 543 is a rod configured to be raised and lowered to engage the cutting die 511 above the bearing surface 513 of the base 509. The actuator 543 may have a lower surface configured to press against the upper surface of the cutting die 511 pushing it downwardly toward the bearing surface 513 of the base 509. The lever may provide a mechanical advantage for depressing the cutting die 511, but it need not be part of the cutting device 300. In some embodiments, the upper surface of the cutting die 511 may form a button configured to be directly manually actuated to cut the stent. The bearing surface 513 is preferably a planar surface configured to hold a sheet of material flat for cutting. The bearing surface 513 may be a recess 544 in the base 509, the recess 544 being sized to hold a piece of material (not shown). Bearing surface 513 may be movable relative to base 509 to expose recess 544 in order to position sheet 101 of material within recess 544.

In some embodiments, the cutting die 511 comprises a single blade that is movable to select the size of the stent being cut. Cutting device 300 may incorporate an actuator 545, such as a dial, button, slider, switch, or other type of actuator configured to adjust the position of mold 511 relative to bearing surface 513 as described above. The actuator 545 may move the base 509 left and right by a threaded screw or other mechanism to change the position of the sheet 101 of material on the bearing surface 513 (e.g., held within the recess 544) relative to the cutting die 511 and thereby modify the width of the support cut from the sheet. Alternatively, actuators 545 may move mold 511 relative to bearing surface 513 to vary the width of the support. The cutting device 300 may incorporate a table 546, the table 546 being configured to be movable relative to the base 509, for example by sliding, rotating or lifting away from the base 509. In some embodiments, the table 546 may slide in a single plane relative to the underlying base 509 while remaining at least partially connected to the base 509. Alternatively, the table 546 may be completely removed from the base 509. Moving the table 546 relative to the base 509 may reveal the recess 544 from below the device area where the cutting die 511 and the actuator 543 are located. This allows loading of the tiles on the load bearing surface without the components of the cutting assembly 500 obstructing the view of the user or physically obstructing access. The cutting device 300 may be a stand alone cutter and need not incorporate a compression or retention mechanism or a transfer mechanism. Rather, the cut stent 105 cut with the cutting assembly 500 may be manually transferred to other tools for preparing the cut stent 105 for deployment through a shaft. Cutting device 300 may be a micro trephine device for minimal modification of biologically derived tissue. The device 300 is configured to cut biologically derived tissue into elongated tissue strips having a length greater than a width. The width may be less than about 3mm and the length may be greater than about 3mm. The biologically derived tissue may be any of the various tissues described herein, including scleral tissue or corneal tissue harvested from a donor of a patient receiving the tissue strip as an implant. The cutting die 511 may include a single sharp edge to trim a larger portion of biological tissue to a desired width. The sharp edge of the die 511 may be substantially straight so that the die 511 may cut a length of tissue. Alternatively, the cutting die 511 may incorporate two sharp edges parallel to each other that are separated by a corresponding width to achieve the desired width of the stent.

The cutting die 511 may include a single blade with a sharp edge or two blades each with a sharp edge. The sharp edge may be formed by a single distal bevel or a double distal bevel. The two blades may be spaced apart from each other in a precise manner to cut a piece of material in a single cutting actuation of the cutting die 511. The two blades may be spaced apart from each other in parallel. In a preferred embodiment (as best shown in fig. 22B-22C), the blades may be mounted at an angle to each other that accommodates the angle of the distal bevel to ensure that the internal spacing between the blades formed by the distal bevel is parallel to each other or orthogonal to the bearing surface. Various embodiments of the cutters described herein may include two blades angularly positioned in this manner. Where the cutter is described as having a single blade, the cutter may also include double blades spaced apart a distance. And where the cutter is described as having double blades spaced apart a distance, the blades may be positioned at an angle relative to each other such that their bevel surfaces are arranged parallel to each other.

Fig. 14D illustrates one embodiment of a cross-correlation of a cutting assembly 500 for cutting a sheet 101 of material. The cutting assembly 500 may include a paper punch type cut. The left side of fig. 14D shows the cutting assembly from a top view and also from a cross-sectional view. Sharp corners or raised sharp edges 525 may protrude from the bearing surface 513. Sharp edge 525 may surround an aperture 527 through bearing surface 513 that opens directly into slot 507 of base 509. A sheet 101 of material may be positioned against bearing surface 513 over hole 527 and against sharp edge 525. The punch 511 may be pushed against the piece of material 101 from above such that the piece of material 101 is cut by the sharp edge 525 and the cut stent 105 is pushed by the punch 511 through the hole 527 into the slot 507. The cut stent 105 may then be disposed within the slot 507 such that a pusher (not shown in fig. 14D) may push the cut stent 105 through the slot 507 toward the tip 508. The terminal region 508 of the slot 507 aligns the cut stent 105 with the longitudinal axis a of the distal shaft 210 so that the stent can be pushed into the distal shaft 210 so that it is ready for delivery. The cartridge may be removed from the cutting device 300 and transferred to the delivery device 400 for deployment into the eye.

Fig. 14E illustrates one interrelated embodiment of a cutting assembly 500 for cutting a sheet 101 of material. The cutting assembly 500 may also incorporate a monetary plunger (money plunger) type of cut. The piece of material 101 may be positioned over the slot 507 in the base 509 and the cutting die 511 pushed against the material 101 from above so that the cutting edge of the die 511 may cut through the piece of material 101 at two locations to cut out the length of the cut stand 105. The compaction tool 517 can be advanced through the aperture 529 in the die 511 to drive the cut stent 105 into the slot 507, pushing it into the terminal end region 508 of the slot 507. A compaction tool 517 or an additional compaction tool 421 can be advanced through the aperture 529 in the die 511 to compress the cut stent 105 in the terminal region 508 of the slot 507 to compact it and align the cut stent 105 with the distal shaft 210 so that it is ready for delivery. The cartridge may be removed from the cutting device 300 and transferred to the delivery device 400 for deployment into the eye.

Fig. 14F-1 through 14F-2 illustrate one interrelated embodiment of a cutting assembly 500 for cutting a sheet 101 of material. The cutting assembly 500 may incorporate a jaw tool 530 to grip the sheet 101 of material. A surgical knife or other cutting tool 535 may be used to trim pieces 101 of material held by jaws 530 to a certain length. The jaws 530 holding the cut stent 105 may be arranged relative to the base 509 and the clamping pressure of the jaws 530 released. The compression tool 517 may be advanced through the jaws 530 to push the cut stent 105 from the jaws 530 into the slot 507 of the base 509 for compressing and compressing the cut stent 105 for delivery as described above.

Fig. 14G illustrates one interrelated embodiment of a cutting assembly 500 for cutting a sheet 101 of material. Cutting assembly 500 may incorporate a plunger 511 configured to compress a sheet 101 of material within a transfer slot 537 of a transfer base 539. Pieces 101 of material may be trimmed to size with a surgical knife or other cutting tool 535. The cut stent 105 within the transfer slot 537 may be transferred by attaching a transfer base 539 to the base 509 with the defined slot 507 in the following manner: the transfer slots 537 are aligned with the slots 507 for compressing and loading the cut stent 105 for deployment using the compression tool 517.

Fig. 14H illustrates one interrelated embodiment of a cutting assembly 500 for cutting a sheet 101 of material. The cutting assembly 500 may incorporate a rotating cylinder 540, the rotating cylinder 540 configured to cut and arrange the cut stent 105 relative to the slot 507 in the base 509 for loading and compressing the stent 105 for delivery. The rotating cylinder 540 may incorporate an internal slot 542 for receiving at least a portion of the sheet 101 of material. Rotation of the cylinder 540 will trim excess tissue that extends beyond the slot 542 in the cylinder 540. Cut stent 105 trimmed to (suitable) length within slot 542 of cylinder 540 is then arranged relative to slot 507 in base 509 for loading and compression for delivery.

Fig. 18A-18H illustrate another embodiment of a cutting device 300, also referred to herein as a trephine box. The cutting device 300 may include a base 302 coupled to an actuator 343. The actuator 343 may be a lever configured to rotate about the pivot axis of the hinge 317. The actuator 343 is configured to actuate the cutting assembly 500 of the cutting device 300 to cut the sheet 101 into the brackets 105. The cutting assembly 500 may include a cutting die 511 attached to at least one blade 547 and a pad 515 movably coupled to the base 302. The cutting die 515 is movable relative to the pad 515 such that the blade(s) 547 can be moved between a retracted position and an extended position. When in the retracted position, the blade(s) 547 remain closed within the pad 515. When in the extended position, the blade 547 penetrates the aperture 527 in the pad 515 and extends through to the lower surface of the pad 515. The base 302 may include a bearing surface 513 positioned below the location of the aperture 527 such that the blade(s) 547 are urged against the bearing surface 513 upon actuation of the cutting die 511. The bearing surface 513 may be located within a recessed area of the base 302 that is shaped and sized to receive the sheet 101 of material to be cut into a bracket by the blade(s) 547. The recessed area of the base 302 may be positioned relative to the aperture 527 such that a desired rack width is obtained when cutting a piece with the blade 547. The area of the recessed bearing surface 513 may extend beyond the edge of the aperture 527 a distance equal to the desired width of the cut stent. The user may place a piece of material within the recessed area such that an edge of the material abuts a distal end of the recessed area such that the piece is cut to a desired width as the blade(s) 547 extend through the aperture 527 and against the bearing surface 513. The area of the base 302 holding the tile need not be concave, but is preferably planar, such that the tile 101 of material is relatively flush with the base 302 and substantially orthogonal to the blade during cutting.

Pad 515, which may be referred to as a door, pressure pad, or compression element, may be coupled to base 302 such that it articulates (articulate) between an open configuration, as shown in fig. 18C-18D, and a closed configuration, as shown in fig. 18C-18D. As shown in fig. 18A-18B. The open configuration reveals the bearing surface 513 of the base 302 so that the tissue piece 101 can be positioned thereagainst. Pad 515 may articulate to a closed configuration over tissue piece 101. Fig. 18E shows the positioning of tablet 101 against bearing surface 513 of base 302 below aperture 527 in pad 515 with the edges of tablet 101 resting against the ends of the recessed area. The blade(s) 547 of the cutting die 511 are in a retracted configuration. The leaf spring(s) 516 may urge the cutting die 511 upward away from the base 302 such that the blade(s) 547 retract into the pad 515. Handle 343 in the open configuration to load tablet 101 can be articulated to the closed configuration above cutting die 511. The articulation of the handle 343 causes its lower surface to press against the upper surface of the cutting die 511 pushing the cutting die 511 downward and compressing the spring 516. Pad 515 may secure and press sheet 101 against bearing surface 513 prior to actuation of blade(s) 547 of cutting assembly 500. Handle 343 may additionally exert pressure on segment 101 urging it against bearing surface 513. Blade(s) 547 of cutting die 511 travel through aperture 527 and penetrate sheet 101 to form a cut stent. When the handle 343 is released, the spring 516 pushes the cutting die 511 upward, causing the blade(s) 547 to move away from the bearing surface 513 back into the bore 527 of the pad 515. The handle 343 can be articulated to the open configuration and the pad 515 is articulated to the open configuration to reveal the cut stent within the recessed area of the base 302. The cut stent may be manually transferred to the loading device 600.

As described above, the cutting die 511 may include a pair of blades 547. The blades 547 may be spaced apart from one another in a precise manner to cut the sheet 101 of material in a single cutting actuation of the lever 343. The blades 547 may be spaced apart from each other in parallel. In a preferred embodiment, the blades 547 are mounted at an angle to each other. The angle between the blades 547 accommodates the angle of the bevel at the distal cutting edge of the blades 547, ensuring that the interior space between the blades 547 (at least the portion of the blades 547 that penetrate tissue) is parallel and straight.

Each blade 547 includes a sharp distal cutting edge formed by at least one distal bevel. The two blades 547 are mounted at an angle relative to each other such that the inner faces are not parallel and the distal ramps are parallel to each other. As described in more detail below, although the inner faces of the blades 547 themselves are not parallel, the distal beveled faces of the blades 547 are parallel to each other and substantially orthogonal to the planar surface of the bearing surface, and thus the tissue pieces are cut. The angulation of the blades is described in more detail below with reference to fig. 22B-22E and 23A-23C. The embodiments of blade cartridges with angled blades described below relate to the blades of the cutting dies of the embodiments shown in fig. 18A-18H, etc.

Fig. 18F is a related embodiment of the cutter of fig. 18A-18E. Fig. 18G is a cross-sectional view of the cutting device 300 of fig. 18F taken along line G-G. Fig. 18H shows the double angled blade 547 of the cutting device 300 with the upper half of the device including the lever actuator 343 removed.

Similar to the embodiment in fig. 18A, the cutting device 300 includes a base 302 coupled to an actuator 343. The actuator 343 may be a lever configured to rotate about the pivot axis of the hinge 317. The actuator 343 is configured to actuate the cutting assembly 500 of the cutting device 300 to cut the sheet 101 into the brackets 105. The cutting assembly 500 may include a cutting die 511 attached to at least one and preferably two blades 547. The cutting die 511 and the blade 547 may be coupled to a pad 515, the pad 515 being movably coupled to the base 302 about the hinge 317. In some constructions, the cutting die 511 and attached blade 547 are movable relative to the pad 515. In other constructions, the cutting die 511 and attached blade 547 are fixed relative to the pad 515 so as to move with the pad 515 about the hinge 317. The blade 547 may be, but need not be, completely enclosed within the pad 515 prior to the cutting actuation. The blade 547 may extend through the lower surface of the pad 515 (either by actuation or simply by being fixed relative to the pad 515 in this manner) such that the blade 547 may be pushed against a bearing surface (not shown in fig. 18G-18H) when the cutting die 511 is actuated.

The bearing surface 513 is sized and shaped to receive the sheet 101 of material to be cut into a holder by the blade 547, and the bearing surface 513 may be located within the recessed region 544 of the base 302. Bearing surface 513 may be a removable planar element configured to be secured to base 302 relative to blade 547 to support sheet 101 of material. The coupling of the bearing surface 513 to the base 302 may be reversible such that the bearing surface 513 may be replaced over time if desired without having to handle the entire cut. The bearing surface 513 may be coupled to the base 302, for example, by one or more fasteners (e.g., screws). Fig. 18G-18H illustrate two holes 541 located near recessed area 544 of base 302 that are sized to receive screws 549 that fix the bearing surface relative to base 302. Other mechanisms 302 that ensure that the bearing surface 513 remains in place within the base are also considered to include a tool-less snap fit or interference fit between the removable bearing surface 513 and the base 302. The planar bearing surface 513 is preferably positioned orthogonal to the sharpened edge of the blade 547 during use, as will be described in more detail below. The blade 547 may also be removably attached to the pad 515 such that if desired, the blade 547 may be replaced if the cutting edge of the blade 547 has become dull.

Pad 515 is coupled to base 302 such that it articulates about hinge 317 between an open configuration and a closed configuration, as described above with respect to fig. 18A-18E. The open configuration reveals the bearing surface 513 of the base 302 such that the patch 101 may be positioned within the cutting device 300 against the bearing surface 513. The pad 515 may be articulated to the closed configuration such that the blade 547 is positioned over the block 547. In some embodiments, closing pad 515 relative to base 302 may hold (with or without compression or pressure) piece 101 within cutter 300 until actuation of lever 343 relative to pad 515 causes blade 547 to cut through piece 101. The return spring 516 may urge the lever 343 and cutting die 511 with attached blade 547 upward away from the bearing surface 513 of the base 302. The return spring 516 thus slightly retracts the blade 547 relative to the pad 515. The lever 343 is movable about the pivot axis of the hinge 317 to close the pad 515 relative to the base 302. The lever 343 is also movable about its own pivot axis of the second hinge 318 to move relative to the pad 515. This articulation relative to pad 515 causes blade 547 to fully cut piece 101 because blade 547 is fully urged against bearing surface 513. Thus, the pad 515 may be used to close the cutting device 300 and to anchor the pieces relative to the base 302 prior to actual cutting, which may occur when the lever 343 is further actuated relative to the pad 515 about the axis 318. The blades 547 of the cutting die 511 may travel further downward relative to the bearing surface 513 to form cut brackets from the sheet 101. Upon release of the lever 343, the spring 516 pushes the cutting die 511 upward such that the blade 547 is moved away from the bearing surface 513. The lever 343 can be articulated about the axis 317 back to the open configuration, thereby opening the pad 515, revealing the bearing surface 513. The cut stent may be manually transferred to a loading device, such as the loading device described herein.

In other embodiments, the blade 547 is fixed relative to the pad 515 such that closing the pad 515 relative to the base 302 alone causes the cutting edge of the blade 547 to pierce and cut the piece 101. The user may actuate the cutting device 300 using the lever 343. The pad 515 is rotatable about the pivot axis of the hinge 317 by a lever 343 to close the pad 515 relative to the base 302. The lever 343 is movable relative to the pad 515 to rotate about the pivot axis of the second hinge 318. This motion compresses return spring 516 and applies a certain amount of cutting pressure to pad 515 pushing it toward tissue on bearing surface 513. The return spring 516 in this configuration provides the user with a tactile sensation that prevents the user from pressing the pad 515 too close against the bearing surface 513 and damaging the cutting edge of the blade 547. The movement of the lever 343 relative to the pad 515 provides the user with some feedback that they have reached the end of travel of the pad 315 to prevent inadvertent damage to the blade 547 during cutting.

The blades 547 may be mounted at an angle relative to each other to accommodate the angle of the bevel of the distal cutting edge. The mounting angle of the blades 547 ensures that the cutting edges are spaced parallel to each other and straight and normal to the bearing surface 513. Fig. 18H shows spacers 526 positioned between blades 547, which provide an angle of blades 547 relative to each other. The angulation of the blades 547 relative to each other and with respect to the geometry of their cutting edges is described in more detail below with reference to fig. 22A-22E and 23A-23C. The description of blade 712 shown in these figures is related to blade 547 of fig. 18A-18E and blade 547 of fig. 18-18H.

The cutting die 511 may include an ejector spring 531 between the blades 547. The ejector spring 531 assists in ejecting the cut stent 105 from between the blades 547 after the cutting action is completed. Ejecting the cut stent 105 out from between the blades 547 allows a user to more easily grasp the cut stent 105, for example with forceps, in order to load the stent into a conveyor. The spring 531 may be a coil spring, leaf spring, foam, or other spring mechanism that helps urge the bracket 105 out from between the two blades 547. The ejector spring is described and illustrated in more detail below in fig. 23A-23C.

Fig. 21A-21B illustrate an interrelated embodiment of a trephine or cutting device 700 having a blade cartridge 710, the blade cartridge 710 having at least one and preferably two blades 712. The two blades 712 allow a user to cut the sheet 101 of material at two locations of the sheet 101 of material in a single actuation to form the stand 105. Blade cartridge 710 may include an upper member or jaw (jaw) 714 and a lower member jaw 716. The upper jaw 714 may include a blade 712 and the lower jaw 716 may include a bearing surface 715. The bearing surface 715 is a planar surface sized to hold the piece 101 of material in a flat orientation relative to the blade 712 such that it may be cut upon actuation. The relative positional terms "upper" and "lower" are used to clearly illustrate the orientation of the components relative to one another and are not intended to be limiting. For example, as shown in the embodiments of FIGS. 18A-18H and 21A-21B, the blades may be positioned on and above the upper and lower components. Alternatively, the blade may be positioned on the lower component and below the upper component.

The cutting device shown in fig. 18A-18H has an actuator configured to cause the blade to cut a piece of material into an implant. The actuator is a lever 343 configured to move the cutting die 511 relative to the sheet. The cutting device shown in fig. 21A-21B also has an actuator configured to cause the blade to cut the piece. In this embodiment, actuation is achieved using a scissor handle 705 that is reversibly coupled to the blade cartridge 710. For example, the handle 705 may include a first handle portion and a second handle portion coupled together in a scissor arrangement by a hinge. The scissor design of the handle 705 opens the blade cartridge 710 attached to the handle 705 when the handle 705 is deployed and closes the blade cartridge 710 when the handle 705 is returned to the closed configuration. Opening the blade cartridge 710 separates the upper and lower jaws 714, 716 of the blade cartridge 710, revealing the bearing surface 715 of the lower jaw 716. This allows the sheet 101 of material to be placed on the load bearing surface 715 prior to cutting. Closing the blade cartridge 710 after positioning the sheet 101 of material on the bearing surface 715 causes the upper jaw 714 to approach the lower jaw 716 of the blade cartridge 710 until the blade 712 pierces the sheet 101 of material on the bearing surface 715. Actuation of the cutting device described herein may vary, including scissor actuation of the handle and actuation of the use of the lever to move the cutting die, as described with respect to fig. 18A-18H. It should be appreciated that the blade cartridges shown in fig. 21A-21B may also be actuated using a lever system similar to that of fig. 18A-18H, and vice versa. Any of a variety of cutting actuations is contemplated herein.

The bearing surface 715 may be a soft plastic material (e.g., silicone having a shore 90A hardness) configured to prevent the blade 712 from dulling or damaging. The bearing surface 715 may incorporate one or more markings to help guide the user in cutting tissue into a desired shape.

The relative configuration of the blade 712 and the bearing surface 715 may vary. For example, blade 712 may be positioned on an upper jaw or a lower jaw, while bearing surface 715 is positioned on the opposing jaw. The scissor handle 705 of trephine device 700 may be versatile in that device 700 may be used by right and left handed users.

As described above, blade cartridge 710 may be removably mounted on handle 705. This allows the blade to be discarded when the cutting edge becomes dull. Blade cartridge 710 may be removed from handle 705 and replaced with a new blade cartridge 710 having a fresh and sharp blade 712. Similarly, the cutting die 511 in the embodiment shown in fig. 18E may be replaced. The cutting assembly 500 includes a cutting die 511 having at least one blade 547, the blade 547 being configured to move relative to the pad 515 and the bearing surface 513 upon actuation of the lever 343. The cutting die 511, along with the blade(s) 547 to which it is attached, may be removed from the pad 515 so that when the blade(s) 547 become dull, the die 511 may be replaced with a new die 511 having a fresh blade 547.

Fig. 21A shows a trephine device 700 in which a blade cartridge 710 is mounted on a handle 705, and fig. 21B shows the blade cartridge 710 removed from the handle 705. Each handle portion of the handle 705 may include a rod-like protrusion 707 at its distal end that is sized, shaped, and length configured to receive a corresponding hole 708 extending through the upper and lower jaws 714, 716 of the blade cartridge 710 from at least the proximal end toward the distal end. The first handle portion has a first protrusion 707 configured to be inserted through the proximal opening into the bore 708 of the lower jaw, and the second handle portion has a second protrusion 707 configured to be inserted through the proximal opening into the bore 708 of the upper jaw. The hole 708 may be positioned through a region of the jaw that avoids interfering with the cutting of the blade 712. Unfolding the handle portion separates the protrusion 707 from the shearing motion and thus the jaws. The attachment between the holes 708 and the protrusions 707 may incorporate features configured to provide reversible, tool-free engagement therebetween, including a slip fit, interference fit, snap fit, bayonet, and other types of attachment. It is desirable to prevent the jaws 714, 716 of the blade cartridge 710 from rotating relative to their respective protrusions 707 to ensure that the blade 712 and the bearing surface 715 remain perpendicular to each other. The protrusion 707 is shown as having a square cross section to prevent rotation of the jaws 714, 716 of the blade cartridge 710 about the axis of the protrusion 707. In an embodiment, the attachment is a slip fit or interference fit onto the protrusion 707 that prevents rotation of the blade cartridge 710 after attachment. Any of a variety of shapes are contemplated (e.g., oval, rectangular, triangular, or other non-circular geometries). The attachment between the handle 705 and the blade cartridge 710 may vary, as is known in the art. The upper and lower attachments may be identical, allowing the user to select a desired orientation relative to the handle 705.

The upper and lower jaws 714, 716 shown in fig. 21B are completely separate components that are not coupled to each other except for their attachment to the protrusion 707 on the handle 705. The upper and lower jaws 714, 716 may also be hingedly coupled to one another.

Blade cartridge 710 also need not be removable from handle 705, although it is preferable to remove blade cartridge 710 from handle 705 so that blade cartridge 710 can be discarded after a single use and handle 705 can be reused for additional blade cartridges 710 after re-sterilization. The handle 705 may be made of a material configured to be re-sterilized, such as metal or plastic. One or more components of the blade cartridge 710 (e.g., the lower jaw 714 having the bearing surface 715) may be made of a material that is not configured to be re-sterilized and is therefore disposable, such as plastic.

Fig. 22A shows the blade 712 of the upper jaw 714 relative to the bearing surface 715 of the lower jaw 716. The blades 712 are spaced apart from each other in a precise manner so as to cut the sheet 101 of material at two locations in a single cutting actuation of the handle 705. In some embodiments, blades 712 are spaced apart parallel to each other. In a preferred embodiment and as best shown in fig. 22B-22C, blades 712 are mounted at an angle to each other that accommodates the angle of the bevel, thereby ensuring that the interior space between blades 712 (at least the tissue-penetrating portion of blades 712) is parallel and straight-sided.

Fig. 22B is a detailed view of blade 712, showing an angled mounting, and fig. 22C is a detailed view of the blade of fig. 22B taken at circle C. Each blade 712 includes a sharpened distal cutting edge 720 formed by at least one distal bevel. The two blades 712 are mounted at an angle relative to each other such that the inner faces are not parallel and the distal slopes are parallel to each other. As described in more detail below, although the inner faces of the blades 712 themselves are not parallel, the distal beveled faces of the blades 712 are parallel to each other and substantially orthogonal to the planar surface of the bearing surface 715, and thus to the cut tissue pieces.

At least the inner face or both the inner and outer faces of each blade 712 may be beveled to form a distal cutting edge 720. The inner face 722 of the blade 712 may be ground to obtain a first cutting surface 724 having a first cutting angle A1. The outer face 723 of the blade 712 may be ground to obtain a second cutting surface 725 having a second cutting angle A2. The first cutting angle A1 may be smaller than the second cutting angle A2. When the inner faces 722 of the blades 712a, 712B are positioned at an angle phi relative to each other (e.g., using the spacers 726), the cutting angle A1 of the first cutting surface 724 allows the first cutting surface 724 of the first blade 712a to be arranged parallel to the first cutting surface 724 of the second blade 712B (as shown in fig. 22B). In other words, the non-parallel angle phi of the blades 712a, 712b relative to each other ensures that the cutting surfaces 724 of the inner faces 722 of the blades 712a, 712b are parallel to each other and are also arranged orthogonal to the bearing surface 715 and, thus, to the tissue being cut resting on the bearing surface 715. The spacer 726 may place the position and distance of the blade(s) 712 within very tight tolerances (e.g., +/-0.1 mm) to facilitate not only obtaining a very consistent and very straight stent 105 from the sheet 101 of material, but also loading the cut stent into a cannula for delivery, as described elsewhere herein.

The angulation of the blades causes the beveled surfaces to be parallel to each other and orthogonal to the bearing surface 715, which prevents the pieces 101 of material located on the bearing surface 715 from being "squeezed" inward during cutting. Eliminating "crush deformation" can make the sheet cut out a more uniform cross section and improve cutting performance. The blade may cut more tissue of different thickness and less damaging to the tissue itself as the blade penetrates the tissue. Although the blade shown has double bevel cutting edges (see fig. 22E), the blade cartridge may also include single bevel blades mounted parallel and planar to each other (see fig. 22D). If the beveled faces face each other at an angle, the resulting interior space between the blades has perfectly parallel and straight faces.

Fig. 23A-23C illustrate an embodiment of an ejector spring 730, the ejector spring 730 being positionable between blades 712 of the blade cartridge 710. The ejector spring 730 assists in ejecting the cut stent 105 from between the blades 712 after the cutting action is completed so that the user may grasp the cut stent 105 (e.g., with forceps) to proceed with the next step of the procedure (e.g., loading the cut stent 105 into a conveyor). Fig. 23A is a perspective view of blade 712. Fig. 23B is a perspective view of one blade 712 being transparent to show the position of spring 730 relative to blade 712 and spacer 726. Fig. 23C is a front end view of blade 712, showing spring 730. An ejector spring 730 (e.g., a coil spring, foam, leaf spring, or other spring mechanism) may be coupled to the spacer 726 positioned between the blades 712. The spring 730 acts to move the cut stent 105 out from between the blades 712. The spring 730 in the spring configuration protrudes between the distal-most ends of the blades (see fig. 23C). This pushes down on any tissue located between blades 712 such that when blade cartridge 710 is opened by deploying handle 705, the tissue is pushed toward the bearing surface 715 of lower jaw 716, rather than between blades 712 in upper jaw 714. Spring 720 is flexible enough to be compressed upward between blades 712 during cutting movement toward bearing surface 715 without affecting the cutting movement of trephine device 700. The cut stent 105 may then be loaded into a delivery cannula for implantation into the eye. The ejector spring 730 may be incorporated into any of the embodiments of the cutters described herein, including the cutting device 300 shown in fig. 18A-18H, to ensure that the cut stent remains grippable by the user.

The relative arrangement of the various components of the cutting assembly with respect to the cutting device may vary. The arrangement described above with reference to the blade being "above" the tile can be performed as easily as the blade being "below" the tile. The directional language used herein is for clarity and understanding purposes and is not intended to limit the apparatus to a particular arrangement.

Fig. 19A-19B illustrate an embodiment of a loading device 600. The loading device 600 may include a base 602 having a distal portion 605, the distal portion 605 including a distal opening or receptacle 606 sized and shaped to receive at least a portion of a tissue cassette (e.g., a nose cone assembly 274). The proximal region of the nose cone assembly 274 may be keyed relative to the receptacle 606 such that it can only be inserted into the receptacle 606 in a single orientation, similar to the keyed connection between the nose cone assembly 274 and the delivery device housing 405. For example, the protrusion 290 of the proximal end of the nose cone assembly 274 may be inserted into at least a portion of the receptacle 606 to align the lumen 238 of the distal shaft 210 with the pusher 620 of the loading device 600. When the handle 643 is in a first configuration relative to the base 602, for example, lifted upward away from the base 602 as shown in fig. 19A, the projection 290 of the nose cone assembly 274 may be inserted into the receptacle 606 of the loading device 600. The handle 643 may be pushed into a second configuration, e.g., rotated toward the base 602, to secure the nose cone assembly 274 relative to the loading device 600 (see fig. 19B). The receptacle 606 may clamp at least one region of the nose cone assembly 274 to secure it relative to the loading device 600.

The loading device 600 may receive the cut stent 105 from the cutting device 300 on a portion of the device 600 opposite the movable plow (plow) 622. The device 600 may incorporate a recess or loading indicia 621 to provide guidance to the user regarding the location of the support 105 relative to the plow 622 where the cut is placed. Plow 622 can be moved forward along base 602 and relative to bracket 105 positioned at marker 621 to urge bracket 105 into alignment with lumen 238 of distal shaft 210. Fig. 20A-20B are cross-sectional schematic views showing bi-directional movement of plow 622 relative to base 602 to align cut stent 105 with the lumen of shaft 210. Fig. 20A shows plow 622 in a retracted configuration such that loading indicia 621 is forward of front surface 624 of plow 622. The cut stand 105 may be positioned at a loading indicia 621 forward of the front surface 624 of the plow 622. Movement of plow 622 in the direction of arrow a pushes cut stent 105 toward terminal region 623 of base 602. The front surface 624 of the plow 622 and the terminal region 623 of the base 602 form a space coaxial with and substantially size-matched to the interior cavity of the shaft (not visible in fig. 20A-20B). The front surface 624 of the plow 622 may be curved so as to form at least a portion of a circle. The terminal region 623 opposite the front surface 624 of the plow 622 may have a curvature that mirrors the curvature of the front surface 624 such that when the plow 622 is placed adjacent the terminal region 623, a tubular structure 625 containing the cut stent 105 is formed (see fig. 20B). The tubular structure 625 formed when the plow 622 is urged into contact with the terminal region 623 of the base 602 may have an inner diameter substantially the same as the inner diameter of the distal shaft. As discussed elsewhere herein, the size of the cut stent 105 may be slightly oversized relative to the lumen of the shaft such that the cut stent 105 is compressed or compacted within the shaft. Similarly, the tubular structure 625 may compress or pinch the cut stent 105 when the plow 622 is placed in contact with the terminal region 623 of the base 602. The relative curvatures of the front surface 624 of the plow 622 and the terminal region 623 of the base 602 can vary, but form a complete shape without gaps when one is mated with the other, such that the bracket 105 is fully contained within the tubular structure 625. The curvature of the front surface 624 may be at least about 90 degrees of a circle and up to about 170 degrees of a circle. The terminal region 623 of the base 602 may have a curvature of at least about 190 degrees up to about 270 degrees of a circle such that the cut stent 105 is enclosed 360 degrees with the anterior surface 624. Any of a variety of curvatures are contemplated herein such that the cut stent 105 may be pushed forward from the marker 621 toward the terminal region 632 such that it is coaxially aligned with the longitudinal axis of the shaft 210. The surface 624 may form a tubular structure 625 with a terminal region 623 that is not circular in cross-section (including oval or other curved shapes).

Once the cut stent 105 is compressed within the tubular structure 625 and aligned with the lumen of the distal shaft, the pusher 620 of the loading device 600 may be used to compress, compact, or otherwise manipulate the cut stent 105 into the lumen of the shaft. The plow 622 can be manipulated in a first direction relative to the base 602, for example, with an actuator operatively coupled to the plow 622. The pusher 620 may be maneuvered in a second direction relative to the base 602, for example, using an actuator operatively coupled to the pusher 620. Any of a variety of actuators are contemplated herein to move plow 622 and/or pusher 620, including dials, buttons, sliders, or other actuators. Plow 622 is movable laterally along an axis A' that is at a 90 degree angle relative to the longitudinal axis A of shaft 210. Pusher 620 may move longitudinally or along longitudinal axis a of shaft 210. Plow 622 aligns the cut stent 105 with the long axis A of the lumen 238 of the shaft 210 and pusher 620 loads the cut stent 105 into the lumen 238 of the shaft 210. The pusher 620 is configured to pass through the tubular structure 625 so that the cut stent 105 moves along the longitudinal axis a into the lumen 238. Once the cut stent 105 is loaded into the nose cone assembly 274, the nose cone assembly 274 may be removed from its attachment to the loading device 600 and coupled to the delivery device 400, as described elsewhere herein.

The cutting device 300 and the loading device 600 may be configured to couple to each other or engage each other such that they form a single system component configured to cooperate with each other. For example, the cutting device 300 may be coupled to the base 602 of the loading device 600. The base 602 of the loading device 600 may include a handle configured to actuate the cutting assembly 500 of the cutting device 300. In this configuration, the cutting device 300 need not incorporate its own handle 343 configured to actuate the cutting assembly 500. Similarly, the pad 515 may be formed from at least a portion of the loading device 600 such that features of the cutting assembly 500 and the loading device 600 cooperate with one another to create a stent. The fixation of tissue, the cutting of tissue, the transfer of a cut scaffold, the loading of a cut scaffold into a tissue cassette may all be combined into a single system or may be separated into different devices.

The cut stent 105 loaded and compressed for delivery may be positioned within at least a portion of the cassette 200, such as within the lumen 238 of the shaft 210. At least a portion of the cartridge 200 may be removed from the cutting device 330 (or loading device 600) and engaged with the delivery device 400 for deploying the stent 105 from the cartridge 200 into the eye. The compression and transfer of the cut stent 105 described above with respect to the cutting assembly 500 prepares the cut stent 105 for delivery without removal of the cut stent 105 from the cassette 200.

The cassette 200 may be coupled with a cutting device 300 having a cutting assembly 500 for cutting the sheet 101 of material and a loading assembly for loading cut stents into the cassette 200. The cartridge 200 may then be removed from engagement with the cutting device 300 so that it may be coupled to the conveyor 400. The cutting device 300 need not incorporate a loading assembly or be coupled to the cartridge 200. For example, the cut stent 105 may be manually transferred from the cutting device 300 to a separate loading device 600, which loading device 600 is coupled with the cartridge 200 to load the cut stent 105 into the cartridge 200 as described above. Such a relationship may include removing and re-engaging the entire cartridge 200 or only a portion of the cartridge 200, such as only the nose cone assembly 274 (e.g., nose cone 275 and shaft 210). Both arrangements are considered herein. The nose cone assembly 274 may be referred to herein simply as the cartridge 200. Where the cartridge 200 is described as being removed from engagement with one device to another, the description pertains to only the nose cone assembly 274 being removed or the entire cartridge 200 being removed. Where the cartridge 200 is described as being configured to engage the delivery device 400, the description pertains to engaging only the nose cone assembly 274 to the delivery device 400 or engaging the entire cartridge 200 to the delivery device 400. Various circumstances of coupling between the cartridge 200 and another component of the system 100 may be the entire cartridge 200 or only a portion of the cartridge 200, such as the nose cone assembly 274.

The piece of material 101 may be placed within a portion of the cartridge 200 for cutting, or the piece of material 101 may be placed within a portion of the cutting device 300 for cutting by the cutting assembly 500 and the cut stent 105 transferred to the cartridge 200 (or only a portion of the cartridge 200, such as the nose cone assembly 274). The cut stent 105 may be transferred into the cassette 200 using the components of the cutting assembly 500 or the cutting device 300, and then the cassette 200 is separated from the cutting device to be coupled with the conveyor. The pieces 101 of material may be placed in the area of the cutting assembly 500 for cutting and then the cut stent 105 manually transferred from the cutting assembly 500 to be pressed in the transfer shaft 210, for example, using a loading device 600 separate from the cutting device 300. A separate device may be used to transfer the cut stent 105 from the cutting assembly 500, including manually. In one embodiment, the system includes a cutting device 300 having a cutting assembly 500. The cut stent 105 from the cutting assembly 500 may be manually transferred (e.g., by forceps) to a transfer device having a compression tool 517 to compress the cut stent 105 into the distal shaft 210. The distal shaft 210, in which the cut stent 105 is compacted, may then be coupled to the delivery device 400 for deployment of the cut stent 105 into the eye. The system may have separate cutting, transferring and conveying devices rather than an integrated device or devices. The cutting assembly 500 shown in fig. 14A-14H may be part of a cutting device. The transfer member may be integral with the cutting device 300 or may be a separate transfer device, such as the loading device of fig. 19A-19B.

The system 100 may include a conveyor 400, the conveyor 400 configured to couple with at least a portion of the cassette 200 holding the cut stent 105. In some embodiments, the entire cartridge 200 with the cut stent 105 is removed from the cutting device 300 and engaged with the conveyor 400 (see fig. 2). In an interrelated embodiment, a portion of the cassette 200 in which the cut stent 105 is positioned is removed from the cutting device 300 and engaged with the delivery device 400 (see fig. 6, 9A-9D).

In the embodiment shown in fig. 5A-5B, the cassette 200 holding the cut stent 105 may be removed and loaded into the conveyor 400. Fig. 5C-5F illustrate loading of tissue cassette 200 within delivery device 400 and deployment of cut stent 105 using delivery device 400. The delivery device 400, along with the cassette 200, may be used to deliver the stent 105 to the site of implantation, such as through an internal delivery path. This allows loading and deploying the stent without having to remove the cut stent 105 from its position within the cassette 200 in order to load the cut stent 105 into the conveyor 400. At least a portion of the cartridge 200 (e.g., the proximal portion 207 of the cartridge 200 or the region of the nose cone assembly 274) may be held by the delivery device 400 and the distal portion 205 of the cartridge 200 may be inserted into the eye.

The delivery device 400 may include a proximal housing 405 and a distal region 410, the proximal housing 405 sized and shaped to be grasped by a single hand of a user, the distal region 410 defining an attachment mechanism 425, such as a receptacle 412 sized to engage at least a portion of the cartridge 200. In one embodiment, the receptacle 412 may be sized to receive at least a length of the proximal portion 207 of the cartridge 200 (see fig. 5C and also see fig. 17A-17D).

In an interrelated embodiment, the attachment mechanism 425 may incorporate another male-to-female attachment mechanism, such as a bayonet connector 413 (see FIGS. 10A-10C, 17A-17C). 17B-17C illustrate a proximal coupler 413a protruding from a proximal region of the nose cone 275 and a corresponding distal coupler 413B protruding from a distal region of the housing 405. The proximal coupler 413a may have a protrusion 290, the protrusion 290 having a shape corresponding to the shape of the receptacle 292 on the distal coupler 413b, thereby forming a keyed interface. The protrusion 290 of the proximal coupler 413a may be inserted into the receptacle 292 on the distal coupler 413b in a first orientation. The nose cone assembly 274 may then be rotated about the axis in a first direction to fix the nose cone assembly 274 relative to the housing 405 (see arrows in fig. 10B). To disengage the nose cone assembly 274 from the housing 405, the opposite operation is performed. The shape of the receptacle 292 and the protrusion 290 may be selected such that rotation of the protrusion 290 relative to the receptacle 292 results in the protrusion 290 being prevented from withdrawing from the receptacle 292. The rotation may be about 90 degrees to about 180 degrees to ensure securement between nose cone assembly 174 and housing 405. This shape is shown as an oval in fig. 10A, but the shape may vary, including rectangular or other geometric shapes as well as freeform shapes. The shape of the projection 290 and receptacle 292 may be selected such that they are coupled together in only a single orientation. Fig. 17A shows that receptacle 292 may be of an elongated shape from top to bottom, and incorporates an upper region 293 that is smaller in size than a lower region 295 of receptacle 292. The protrusion 290 may have a corresponding shape that can only be inserted into the receptacle 292 when the smaller upper region of the receptacle 292 is at the top and the larger lower region is at the bottom. When inserted into receptacle 292, projection 290 may be rotated, for example, 90 degrees in a clockwise direction relative to receptacle 292 to secure nose cone assembly 174 relative to housing 405.

As mentioned above with respect to the cutting device 300, the attachment mechanism 425 may be keyed such that the cartridge 200 with the cover 214 in place on the base 224 may be received within the attachment mechanism 425 or otherwise engage the attachment mechanism 425 in a single orientation. When the cartridge 200 is coupled with the attachment mechanism 425 of the housing 405, the shaft 210 of the cartridge 200 extends outwardly from the housing 405 in a distal direction. The keying feature of the attachment mechanism 425 may prevent attachment in the wrong orientation. The attachment mechanism 425 may also provide the user with a secure connection with tactile feedback to indicate when the connection is fully engaged. The attachment mechanism 425 is also sized to ensure that the lumen 238 of the shaft 210 is aligned with an internal mechanism of the delivery device 400 (e.g., the push rod 420).

The attachment mechanism 425 of fig. 5A-5C may be a receptacle 412 that is deep enough to accommodate the length of the proximal portion 207 of the cartridge 200 while the shaft 210 remains outside of the receptacle 412. The flexible hooks 422 may extend into at least a portion of the receptacle 412 (see fig. 5C). The distal end 424 of the hook 422 may be received within a correspondingly shaped detent 272 near the proximal end region of the tissue cassette 200. As the cartridge 200 slides within the receptacle 412, the distal end 424 of the hook 422 may slide through the proximal end 207 of the cartridge 200 and insert into the pawl 272. The flexibility of the hook 422 allows the hook 422 to be pushed upward as the distal end 424 of the hook 422 advances through the first region of the cartridge 200 and to bend back downward as the distal end 424 advances further, thereby engaging the pawl 272 (see fig. 5D). The spring-loaded hooks 422 that engage the detents 272 may provide a tactile and/or audible "click" to inform the user that the cartridge 200 is fully installed within the delivery device 400, held and ready to deliver the rack 105.

One or more actuators 415 may be positioned on an area of the housing 405. The actuator 415 may also be manipulated by a single hand of the user, such as with a thumb or finger. The configuration of the actuator 415 may vary. For example, the actuator 415 may include any of a variety of knobs, buttons, sliders, dials, or other types of actuators (as will be described in more detail below) configured to move one or more components of the delivery device 400.

The delivery device 400 may include a push rod 420 configured to be moved by one or more actuators 415. Once the desired position is reached with the distal end of the shaft 210, a push rod 420 (also referred to herein as a pusher or hold down tool) may be used with the cartridge 200 to transfer the stent 105 from the cartridge 200. The push rod 420 may be sized and shaped to complement the interior dimensions of the shaft 210. For example, in the case where the shaft 210 of the cartridge 200 has a rectangular cross-sectional shape, the cross-section of the push rod 420 may be rectangular. This allows the push rod 420 to effectively push the cut stent 105 through the lumen 238 of the shaft 210.

The push rod 420 may be fully retracted in the proximal position prior to coupling the tissue cassette 200 into the delivery device 400, so that the push rod 420 does not interfere with loading of the cassette 200. Once the cartridge 200 is installed and held within the delivery device 400, as shown in fig. 5D and 9B, the push rod 420 may be advanced distally through a proximal port in the cartridge 200 and into the lumen 238 of the shaft 210 (see fig. 5E and 9C). In some embodiments, the push rod 420 may be advanced through the lumen 238 and out the distal opening 230 of the lumen 238 to deploy the stent 105. In other embodiments, the push rod 420 is advanced to a distal position within the lumen 238 near the proximal end of the stent 105 and the shaft 210 is proximally withdrawn while the push rod 420 remains stationary to deploy the stent 105 (see fig. 5F and 9D).

The shaft 210 may be proximally withdrawn by movement of the cartridge 200 relative to the delivery device 400 in a proximal direction while the push rod 420 remains stationary in order to deploy the stent 105 within the eye (see fig. 5F and 9D). Thus, the push rod 420 may act as a stop, preventing the bracket 105 from following the shaft 210 as it retracts. The result is that stent 105 is ejected from shaft 210 and left in the tissue. In other embodiments, both the cartridge 200 and the push rod 420 may be moved to effect deployment of the stent from the shaft 210. In some embodiments, the push rod 420 can be advanced relative to the shaft 210 to fully deploy the stent 105 from the lumen.

In some embodiments, the push rod 420 may be coupled to the first actuator 415 and the cartridge 200 may be coupled to the second actuator 415. The first and second actuators 415 may be slides, buttons, or other configurations or combinations of actuators configured to advance and retract their respective components. The first actuator 415 coupled to the push rod 420 can be proximally withdrawn such that the push rod 420 is in its proximal-most position when the cartridge 200 is engaged by the attachment mechanism 425 of the delivery device 400. The user may advance the first actuator 415 to distally advance the push rod 420 to advance the stent 105 within the lumen 238 of the cartridge 200 toward the distal opening 230 of the shaft 210. After the cut stent 105 is ready to enter its distal position within the lumen 238, the shaft 210 of the cartridge 200 may be used to dissect tissue of the eye until the target position is reached. Once the shaft 210 is in place to deploy the stent 105 in the eye, a first actuator 415 coupled to the push rod 420 may remain in the distal position and a second actuator 415 is actuated (e.g., retracting a slider or push button) to retract the cartridge 200 a distance relative to the delivery device 400. This relative movement of the shaft 210 of the cartridge 200 relative to the push rod 420 is from deploying the stent 105 from the lumen 238 to the anatomy. The stent 105 may be deployed from the lumen 238 by pushing the push rod 420 such that the stent 105 is fully exposed from the lumen 238.

Fig. 5E shows the cassette 200 mounted within the receptacle 412 of the conveyor 400 such that there is a space between the end of the receptacle 412 and the nearest end of the cassette 200. The depth of this space defines the maximum distance 200 that the cartridge can retract. The stent 105 is positioned adjacent the distal opening 230 relative to the lumen 238 and the push rod 420 is advanced to its distal position such that the distal end of the push rod 420 abuts the proximal end of the stent 105. The distal end 424 of the hook 422 remains within the pawl 272 and the second actuator 415 has not yet been actuated. The proximal end 426 of the hook 422 is coupled to a spring 430. When the second actuator 415 is in a resting state prior to actuation, the hook 422 is urged distally into the first configuration. As the hook 422 is pushed distally into the first configuration, the spring 430 is compressed between the proximal end 426 of the hook 422 and the distal end of the spring 430 housing. When the second actuator 415 is actuated (e.g., pushed downward), the spring 430 is released and pushes the proximal end 426 of the hook 422 toward the proximal end of the housing 405. The hook 422 moves proximally and drags the cartridge 200 with it, which couples with the hook 422 due to the engagement of the distal end 424 of the hook 422 within the pawl 272. The distance the hook 422 moves proximally thus retracts the cartridge 200 deeper into the receptacle 412. The push rod 420 may remain stationary during retraction of the cartridge 200. Relative movement 420 between the shaft 210 and the push rod 420 deploys the stent 105 from the lumen 238 (see fig. 5F).

It should be appreciated that additional distal movement of the push rod 420 may be used to assist in deploying the stent 105 from the lumen 238. It should also be appreciated that push rod 420 advancement and cartridge 200 retraction may be controlled by dual actuator 415 as described above or by a single actuator 415 capable of effecting movement of both the pusher and cartridge 200 depending on the degree of actuation. Furthermore, during the process of using the push rod 420 as a plunger, the shaft 210 may be used to inject a viscous material, such as a viscoelastic material. The method of implantation and delivery of the stent 105 is described in more detail below.

Fig. 11A-11C illustrate the step of deploying the stent by using a first actuator 415a (which in this case may be a slider) of the delivery device 400 to move the pusher from a first loading position (fully retracted) to a second ready position (at least partially advanced). The first loading position retracts the pusher away from the distal region of the delivery device 400, allowing the nose cone assembly 274 (or the entire cartridge 200) to be coupled to the delivery device 400. The second ready position advances the pusher toward the distal end of the delivery device 400 to advance the cut stent 105 through the lumen 238 of the shaft 210. Preferably, the pusher is advanced to the second armed position prior to insertion of the shaft 210 through the cornea. The transfer device 400 may additionally incorporate a movable guard 432 arranged to prevent the user from inadvertently pushing the slider past the second ready position. The guard 432 may be pushed downwardly toward the housing 405 of the transfer device such that the second actuator 415b is covered by the guard 432, thereby preventing the second actuator 415b from being accidentally activated. The guard 432 has a length such that the guard 432 extends over at least a portion of the slider track 435 (or has a feature 433 extending within at least a portion of the slider track 435) to prevent further distal movement of the first actuator 415a in addition to blocking the second actuator 415B (fig. 11B). Once the bracket 105 is advanced to the ready position and ready for deployment into the eye, the guard 432 can be rotated upward to clear the second actuator 415b and remove the feature 433 from the track 435. The first actuator 415a is free to slide further distally along the track 435 and the second actuator 415b can be depressed (fig. 11C). The guard 432 may also be completely removed from the device 400 or the device 400 does not include any guard 432. The housing of the device 400 may include one or more markers 434 that are intended to provide feedback to the user regarding the position of the push rod 420 through the shaft 210. Pushing the push rod 420 to one or more positions relative to the housing may also provide tactile feedback to the user, as described elsewhere herein.

Fig. 12A-12D illustrate, in cross-section, the delivery device 400 prior to advancing the push rod 420 to the second position and after advancing the push rod 420 to the second position. Once the nose cone assembly 274 is attached to the delivery device 400, the first actuator 415 and the push rod 420 may be advanced from the initially retracted first position to the second position. The first actuator 415a and the pusher bar 420 may be advanced to the second position, resulting in insertion of the pusher bar 420 into the interior cavity 238 behind the material to be delivered (e.g., the cut stent 105). The guard 432 having a protruding feature 433 on its underside may prevent the first actuator 415a from sliding past the second position. The positioning of the second position is designed to place the leading face of the push rod 420 at a predetermined distance (e.g., 6 mm) from the distal tip of the shaft 210. Once the user has created the desired breach and is ready to deliver material from the lumen, the push rod 420 can be advanced to its third, forward-most position (with the guard 432 unobstructed, or otherwise removed or absent from the device 400). The second actuator 415b may be engaged to release the material from the shaft 210. The second actuator 415b, as described elsewhere herein, may retract the shaft 210 while the push rod 420 remains stationary, eventually releasing the stent 105 from the lumen. Nose cone assembly 274 is withdrawn while pushrod 420 remains stationary. The push rod 420 may also be advanced to deploy the stent 105 from the lumen 238. The stent 105 may be deployed from the lumen 238 such that at least a portion of the stent 105 is positioned between layers of tissue, such as in the supraciliary cavity between ciliary tissue and scleral tissue, or in schlemm's canal. The stent 105 may be deployed such that it is positioned within the supraciliary cavity such that at least the distal region is positioned between the ciliary tissue and the sclera and the proximal end is within the supraciliary space. When positioned within the supraciliary space, the proximal end need not extend into the anterior chamber. Preferably, the proximal end of the scaffold 105 is positioned such that it remains flush with the split between the ciliary tissue and scleral tissue and does not extend into the anterior chamber. The presence of one or more fenestrations 276 within the shaft 210 and/or a substantially transparent or translucent outer tube member 278 forming the distal end region 212 of the shaft 210 may assist in positioning the stent 105 flush with the split by helping to visually inspect the lumen 238 and the implant within the lumen 238 as the stent 105 is pushed distally through the lumen 238.

Maintaining a fixed position of the push rod 420 during deployment of the stent 105 may be aided by a mechanical stop (backstop) 450. The stop 450 may prevent the push rod 420 from being pushed proximally by the bracket 105 within the lumen 238 of the shaft 210. The backstop 450 may be located within the housing 405 below a slider rail 435 in the housing 405 through which the actuator 415a slides. The stop 450 is sized and shaped to engage a corresponding region of the actuator 415a located within the housing 405. An outer portion of the actuator 415a extends outside of the slider track 435 of the housing 405 and is configured for engagement by a user of the actuator 415a. The inner portion of the actuator 415a is located within the housing 405 and is coupled to the proximal end region 444 of the push rod 420. Advancement of the actuator 415a along the slider track 435 pushes the push rod 420 distally relative to the housing 405 such that the distal end of the push rod 420 is pushed toward the opening of the shaft 210. The interior portion of the actuator 415a located within the housing 405 may also include a flex portion 452 having a protrusion 451 extending upward toward the slider track 435. The flex portion 452 is movable between a compressed position and a relaxed configuration. When the actuator 415a is in the fully retracted position and slid to the proximal end of the slider track 435, the flex portion 452 is urged downwardly by the inner surface of the housing 405 to the compressed position. As actuator 415a slides distally along slider track 435, projection 451 also slides along the interior of housing 405 until it reaches stop 450. When the position of the backstop 450 is reached, the flex portion 452 relaxes upwardly to a relaxed configuration. The projection 451 on the upper surface of the flex portion 452 contacts the upper end of the housing 405, and the proximal surface of the projection 451 engages the distally facing surface of the stop 450. The engagement between the surfaces of the stop 450 and the projection 451 prevents any unintended proximal movement of the actuator 415a, thereby preventing proximal movement of the push rod 420 that may occur during deployment of the stent 105 from the shaft 210.

Fig. 17G-17H illustrate a feature 433 on the button guard 432 where an outer portion of the actuator 415a outside of the housing 405 abuts against a protrusion within the slider track 435. The projection 451 engages against the stop 450. When the actuator 415a reaches this position, the stent 105 has been advanced to a ready position within the shaft 210 and is ready to be deployed into the eye. The button guard 432 may be rotated upward away revealing the second actuator 415b. Depressing the second actuator 415b causes the bracket 105 to be deployed from the shaft 210, for example by retracting the shaft 210 while the push rod 420 remains fixed in the armed position. The stop 450 prevents the push rod 420 from moving proximally with the shaft 210. If desired, the user may retract the actuator 415a by lifting the front end region of the actuator 415a to cause the rear end having the projection 451 to flex downward due to the flexibility of the flex portion 452 (see FIG. 17I). Downward movement of the rear end of the actuator 415a disengages the projection 451 from the stop 450, allowing the actuator 415a to move proximally along the sled track 435, for example, to reset the instrument for further use.

The delivery device 400 and cartridge 200 (or nose cone assembly 274) may be single-use devices that incorporate a lock-out device after deployment of the stent 105, or may be sterilized and reused. The above-described resetting of actuator 415a allows for reuse of housing 405 after deployment of stent 105. Fig. 13A-13B illustrate an additional reset mechanism 436 so that the deployment configuration can be reset and the delivery device 400 can be reused. Actuation of the return mechanism 436, such as a forward slide button, may return the deployment structure to the armed position. The return mechanism 436 may also be performed by pulling the nose cone assembly 274 or the bayonet connector 413 of the delivery device 400 distally until the second actuator 415 returns to its initial armed position. If desired, the nose cone assembly 274 may be removed from the delivery device 400 and additional material loaded into the shaft 210 as described elsewhere herein. The delivery device 400 may be provided in an actuated or non-armed state and the user arms the instrument at the time of use. The delivery device 400 may also be a single use device that cannot be reset after deployment, such as by the absence of a reset mechanism 436.

The nose cone assembly, which is translatable between the delivery device and the cutting device, may be mounted relative to the main assembly of the cutting device. The tissue pieces may be cut by the cutting device and loaded into the nose cone assembly, which in turn may be transferred from the main assembly of the cutting device back to couple with the delivery device for deployment in the patient. The configuration of the nose cone assembly may vary, including any of the transferable cartridges described herein. In one embodiment, the nose cone assembly may be mounted relative to the cutting assembly by coupling the proximal end of the nose cone to the base such that the longitudinal axis of the lumen of the shaft extending distally from the nose cone is aligned with the longitudinal axis of the corresponding catheter exiting from the slot. Tissue pieces may be placed in the loading region of the base relative to a movable stop plate on the main assembly. The loading zone area and the movable stop plate may both be part of the base of the main assembly. The tiles may be placed inside one or more alignment features of the loading zone and slid forward into the cutting zone until the tiles abut the stopper plate. Once positioned against the stop plate, the tissue pieces are positioned at the designated width by the cutter. Thus, the stop plate provides a calibrated stop point for the tissue piece prior to cutting. Elements designed to secure a tissue piece in this position may be activated, e.g., lowered over the tissue piece to hold the tissue in place, and optionally compressed to a particular height prior to cutting. Once the retaining plate is lowered onto the pieces to hold them in place, the cutting bar may be lowered to cut the tissue pieces with one or more blades. The retainer plate and the retention plate can be removed from the cut scaffold and the remainder of the tissue piece removed from the assembly. The cut stent may be loaded using a tissue loader sled. The tissue loader slide can push the cut stent into position relative to the longitudinal axis of the shaft in the nose cone assembly. For example, the tissue loader slide may be placed in position and slid as far forward as possible until the slide abuts a boss on the main assembly, indicating that the cut stent is fully delivered into the compression channel and ready to advance into the shaft of the nose cone assembly. An elongate tool, such as a tissue pusher rod, may be inserted into the main assembly along the longitudinal axis to push the cut stent from the main assembly into the shaft of the nose cone assembly. The rod may be designed to push the tissue slide toward the end of the nose cone assembly without pushing the cut stent completely out of the lumen of the shaft. The nose cone assembly may then be disconnected from the main assembly and attached to a delivery device for deployment into a patient.

In other embodiments, the cassette 200 itself holds the tissue pieces for cutting. For example, fig. 3A shows that the cover 214 of the cartridge 200 can be removed from the slot 214 in the base 224, revealing the recess 221. The pieces 101 of material may be manually loaded into the recesses 221. The sheet 101 of material may be sized to be received within the recess 221 or may be trimmed to ensure that it is sized to be received within the recess 221. The cover 214 of the cartridge 200 is replaced onto the base 224 and advanced through the slot 215 until the lower portion 222 of the cover 214 engages the sheet 101 of material to capture it against the projection 271. When in the closed configuration, the cover 214 may compress and/or tension the sheet 101 of material within the cartridge 200. Fig. 2 illustrates that the loaded tissue cassette 200 may be mounted into the receptacle 306 of the cutting device 300 with the handle 343 in an open configuration. Once installed, the cutting member 312 may be actuated by lowering the handle 343 toward the base 302, pushing the blade 344 toward the sheet 101 of material until the blade 344 of the cutting member 312 cuts completely through the sheet 101 of material (FIG. 4B). While the blade 344 is still in the fully cut position relative to the cartridge 200, the pusher 320 of the cutting device 300 may be pushed distally to prepare the shaft 210 and place the now cut stent 105 within the lumen 238 of the shaft 210 from the lumen 238 toward the opening 230 near the distal region 212 of the shaft 210. The pusher 320 may be retracted from the cartridge 200 and the cartridge 200 removed from the cutting device 300. As described elsewhere herein, removing the cartridge 200 from the cutting device 300 may include removing the entire cartridge 200 from the device 300 or disassembling the nose cone assembly 274 of the cartridge 200, as shown in fig. 6.

The prepared tissue cassette 200 with the cut scaffold 105 positioned within the lumen 238 of the shaft 210 may be mounted with the delivery apparatus 400 (e.g., inserted into the receptacle 412 or attached by the bayonet connector 413 or other attachment mechanism 425). The push rod 420 of the delivery device 400 is withdrawn in the proximal-most position and the cartridge 200 is coupled to the delivery device 400. The push rod 420 may be advanced using the first actuator 415 from a first retracted position suitable for loading the cassette 200 to a second ready position such that the delivery device 400 and the cassette 200 are now ready for use by a patient.

In general, the stent 105 positioned within the shaft 210 may be implanted through a transparent corneal or scleral incision formed using the shaft 210 or a device separate from the cartridge 200. A viewing lens, such as an anterior chamber angle lens, may be positioned near the cornea. The viewing lens is capable of viewing an interior region of the eye, such as the scleral spur and scleral limbus, from a position in front of the eye. The viewing lens may optionally include one or more guide channels sized to receive the shaft 210. Endoscopes may also be used to aid in visualization during delivery. Ultrasound guidance may also be used using high resolution biomicrographs, OCT, etc. Alternatively, a small endoscope may be inserted through another limbal incision in the eye to image the eye during implantation.

The distal tip 216 of the shaft 210 may penetrate the cornea (or sclera) to access the anterior chamber. In this regard, a single incision may be made in the eye, such as within the limbus. In one embodiment, the incision is very close to the limbus, for example at the limbus level or within 2mm of the limbus in the clear cornea. The shaft 210 may be used to make an incision or a separate cutting device may be used. For example, a knife tip device or diamond knife may be used initially to gain access to the cornea. A second device having a blade tip may then be advanced over the tip, with the plane of the blade positioned coincident with the anatomical plane. The blade tip device may be a shaft 210.

The corneal incision may have a size sufficient to allow the shaft 210 to pass through. In one embodiment, the incision is about 1mm in size. In another embodiment, the incision is no greater than about 2.85mm in size. In another embodiment, the incision is no greater than about 2.85mm and greater than about 1.5mm. It was observed that the incision up to 2.85mm was a self-sealing incision.

After insertion through the incision, the shaft 210 may be advanced into the anterior chamber along a pathway that enables the stent 105 to be delivered from the anterior chamber to a target location (e.g., the supraciliary or suprachoroidal space). By positioning the shaft for access, the shaft 210 may be advanced further into the eye such that the distal-most end 216 of the shaft 210 penetrates tissue at the canthus, such as the iris root or an area of the ciliary body, or the iris root portion of the ciliary body near its tissue boundary with the scleral spur.

Scleral spur is an anatomical landmark on the corner wall of the eye. Scleral spur is above iris level but below trabecular meshwork level. In some eyes, the scleral spur may be masked by and directly behind the lower band of the trabecular meshwork that deposits the pigment. The shaft 210 may travel along a path toward the canthus and scleral spur such that the shaft 210 passes near the scleral spur en route to the supraciliary cavity, but does not have to penetrate the scleral spur during delivery. Rather, the shaft 210 may abut the scleral spur and move downward to dissect the tissue boundary between the sclera and ciliary body, with the anatomical entry point beginning just below the scleral spur, near the iris root, or near the iris root portion of the ciliary body. In another embodiment, the delivery pathway of the implant intersects the scleral spur.

The shaft 210 may approach the canthus from the same side of the anterior chamber as the deployed position so that the shaft 210 does not have to be advanced through the iris. Alternatively, the shaft 210 may approach the canthus from passing through the anterior chamber AC such that the shaft 210 advances across the iris and/or anterior chamber toward the opposite canthus. The shaft 210 may approach the canthus along a variety of pathways. The shaft 210 does not necessarily traverse the eye and does not intersect the central axis of the eye. In other words, the corneal incision and the location where the stent 105 is implanted at the corner of the eye may be in the same quadrant when viewed along the optical axis looking toward the eye. In addition, the path of the stent 105 from the corneal incision to the canthus should not pass through the centerline of the eye in order to avoid touching the pupil.

The shaft 210 may be advanced continuously into the eye, for example about 6mm. The anatomical plane of the shaft 210 may follow the curve of the inner scleral wall such that the stent 105 mounted in the shaft, for example, after penetrating the iris root or iris root portion of the ciliary body CB, may passively dissect the boundary between the scleral spur and the tissue layers of the ciliary body CB such that the distal region of the stent 105 extends through the supraciliary cavity and then further between the sclera and the tissue boundary of the choroid forming the suprachoroidal cavity.

Once properly positioned, the stent 105 may be released from the shaft 210. In some embodiments, the stent 105 may be released by withdrawing the shaft 210 while the push rod 420 prevents the stent 105 from withdrawing with the shaft 210.

Once implanted, the stent 105 forms a fluid communication pathway between the anterior chamber and a target pathway (e.g., supraciliary or suprachoroidal space). As described above, the stent 105 is not limited to implantation in the suprachoroidal space or supraciliary space. The stent 105 may be implanted at other locations that provide fluid communication between the anterior chamber and a location in the eye, such as schlemm's canal or the subconjunctival site of the eye. In another embodiment, the stent 105 is implanted to form a fluid communication pathway between the anterior chamber and schlemm's canal and/or a communication pathway between the anterior chamber and the subconjunctival site of the eye. It should be understood that the devices described herein may also be used to deliver stents transsclerally as well as from an endoprosthesis.

As described above, the material used to form the scaffold may be impregnated with one or more therapeutic agents for additional treatment of the ocular disease process.

The scaffolds described herein can be used to prevent or treat a variety of systemic and ocular diseases, such as inflammation, infection, cancerous growth. More specifically, eye diseases such as glaucoma, proliferative vitreoretinopathy, diabetic retinopathy, uveitis, keratitis, cytomegalovirus retinitis, cystoid macular edema, herpes simplex virus, and adenovirus infection can be treated or prevented.

The following classes of drugs may be delivered using the device of the present invention: antiproliferatives, antifibrotic agents, anesthetics, analgesics, cell transport/fluidity impending agents (e.g., colchicine, vincristine, cytochalasin B, and related compounds); anti-glaucoma agents including beta-blockers such as timolol, betaxolol, atenolol and prostaglandin analogs-bimatoprost, travoprost, latanoprost, and the like; carbonic anhydrase inhibitors such as acetazolamide, methazolamide, dichlorphenamine, and methazolamide; and neuroprotective agents such as nimodipine and related compounds. Other examples include antibiotics such as tetracycline, aureomycin, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, gentamicin, and erythromycin; antibacterial agents such as sulfonamides, sulfacetamides, sulfadimazole and sulfaisoxazole; antifungal agents, such as fluconazole, furacilin, amphotericin B, ketoconazole, and related compounds; antiviral agents such as trifluoretortin, acyclovir, ganciclovir, DDI, AZT, foscamet, vidarabine, trifluormeoside, herpesvirus, ribavirin, protease inhibitors and anti-cytomegalovirus agents; antiallergic agents such as methamphetamine; chlorphenamine, pyrilamine and phenylpyridine; anti-inflammatory agents such as hydrocortisone, dexamethasone, fluocinolone acetonide, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, and triamcinolone; decongestants such as phenylephrine, naphazoline, and tetrazine; miotics and anticholinesterases, such as pilocarpine, carbachol, diisopropyl fluorophosphate, iodophosphine, and ergoline bromide; mydriatic agents such as atropine sulfate, cycloproteol, vaptane, scopolamine, tokyo, and eukatolidine; sympathomimetics, such as epinephrine and vasoconstrictors and vasodilators; ranibizumab, bevacizumab and triamcinolone.

Non-steroidal anti-inflammatory drugs (NSAIDs) may also be delivered, such as cyclooxygenase-1 (COX-1) inhibitors (e.g., acetylsalicylic acid, such as Bayer AG from Lewkusen, germany)Ibuprofen, e.g. Wyeth, collegeville/>, from pennsylvaniaAntiphlogistic pain; mefenamic acid), COX-2 inhibitors (Pharmacia company/>, peapack, N.J.)COX-1 inhibitors), including prodrugs/>Immunosuppressants, e.g. Sirolimus (Wyeth, collegeville/>, pa., W/E)) Or Matrix Metalloproteinase (MMP) inhibitors (e.g., tetracyclines and tetracycline derivatives) that act early within the inflammatory response pathway. Anticoagulants, such as heparin, antifibrinol, fibrinolysin, antithrombin, and the like, may also be delivered.

Antidiabetic agents that may be delivered using the present device include acetohexylamine, chlorsulfonylurea, glipizide, glibenclamide, tolazolamide, tolbutamide, insulin, aldose reductase inhibitors, and the like. Some examples of anticancer agents include 5-fluorouracil, doxorubicin, asparaginase, azacytidine, azathioprine, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, cyclosporin, cytarabine, dacarbazine, daunorubicin, doxorubicin, estramustine, etoposide, emamectin, feveridine, fluorouridine, fludarabine, fluorouracil, fluoxymesterone, flutamide, goserelin, isosulfonylurea, leuprorelin, levamisole, lomustine, nitrogen mustard, melphalan, mercaptopurine, methotrexate, mitotane, pentastatin, pipobroman, procamycin, procarbazine, sha Gemo stamycin, streptozocin, tamoxifen, paclitaxel, teniposide, thioguanine, uracil mustard, vinblastine, vincristine, and vinblastine.

The present devices can be used to deliver hormones, peptides, nucleic acids, carbohydrates, lipids, glycolipids, glycoproteins, and other macromolecules. Examples include: endocrine hormones such as pituitary, insulin-related growth factors, thyroid and growth hormone; a heat shock protein; immune response modifiers such as muramyl dipeptide, cyclosporin, interferons (including alpha, beta and gamma interferons), interleukin 2, cytokines, FK506 (an epoxy-pyrido-oxazol cyclotricoxine, also known as tacrolimus), tumor necrosis factor, prastatin, thymopentapeptide, transforming factor beta2, erythropoietin; anti-tumor proteins (e.g., anti-vascular endothelial growth factor, interferon), and the like, and anticoagulants, including antithrombin. Other examples of macromolecules that may be delivered include monoclonal antibodies, brain Nerve Growth Factor (BNGF), brain nerve growth factor (CNGF), vascular Endothelial Growth Factor (VEGF), and monoclonal antibodies to these growth factors. Other examples of immunomodulators include tumor necrosis factor inhibitors, such as thalidomide.

In various embodiments, the description is with reference to the accompanying drawings. However, certain embodiments may be practiced without one or more of these specific details, or in combination with other known methods and constructions. In the description, numerous specific details are set forth, such as specific configurations, dimensions, and processes, in order to provide a thorough understanding of the embodiments. In other instances, well-known processes and manufacturing techniques have not been described in particular detail so as not to unnecessarily obscure the description. Reference throughout this specification to "one embodiment," "an embodiment," "one implementation," "an implementation," etc., means that a particular feature, structure, configuration, or characteristic described is included in at least one embodiment or implementation. Thus, appearances of the phrases "one embodiment," "an embodiment," "one implementation," "an embodiment," and the like appearing in various places throughout the specification are not necessarily referring to the same embodiment or implementation. Furthermore, the particular features, structures, configurations, or characteristics may be combined in any suitable manner in one or more embodiments.

Relative terms are used throughout the description to refer to relative positions or orientations. For example, "distal" may indicate a first direction away from a reference point. Similarly, "proximal" may indicate a position in a second direction opposite to the first direction. The reference point as used herein may be the operator such that the terms "proximal" and "distal" refer to the operator using the device. The device region closer to the operator may be described herein as "proximal" and the device region farther from the operator may be described herein as "distal". Similarly, the terms "proximal" and "distal" may also be used herein to refer to the anatomical location of the patient from the perspective of the operator or from the point of entry or along the insertion path from the point of entry of the system. Thus, a proximal position may refer to a position within the patient that is closer to the entry point of the device along the insertion path toward the target, while a distal position may refer to a position within the patient that is farther from the entry point of the device along the insertion path toward the target. However, these terms are provided to establish a relative frame of reference and are not intended to limit the use or orientation of the apparatus to the particular configuration described in the various embodiments.

As used herein, the term "about" refers to a range of values that includes the specified value, which one of ordinary skill in the art would consider reasonably similar to the specified value. In some aspects, "about" means within standard deviation using measurements generally acceptable in the art. In some aspects, "about" refers to a range extending to +/-10% of the specified value. In some aspects, "about" includes a specified value.

While this specification contains many specifics, these should not be construed as limitations on the scope of what may be claimed, but rather as descriptions of features specific to particular embodiments. Certain features that are described in this specification in the context of separate embodiments can also be implemented in combination in a single embodiment. Rather, the various features described in the context of separate embodiments can also be implemented in multiple embodiments separately or in any suitable subcombination. Furthermore, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a subcombination or variation of a subcombination. Similarly, although operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. Only a few examples and embodiments are disclosed. Variations, modifications, and enhancements to the described examples and embodiments, as well as other embodiments, may be made based on the disclosure.

In the description and claims above, phrases such as "at least one of … …" or "one or more of … …" may appear after a connected list of elements or features. The term "and/or" may also occur in a list of two or more elements or features. Such phrases are intended to mean any element or feature listed alone or in combination with any other recited element or feature unless otherwise implicitly or explicitly contradicted by context in which it is used. For example, the phrases "at least one of a and B", "one or more of a and B", and "a and/or B" are each intended to mean "a alone, B alone, or a and B together". Similar explanations are also intended to be used for lists containing three or more items. For example, the phrases "at least one of A, B and C", "one or more of A, B and C", "A, B and/or C" each mean "a alone, B alone, C, A alone and B together, a and C together, B and C together, or a and B and C together.

The use of the term "based on" in the foregoing and claims is intended to mean "based, at least in part, on" such that unrecited features or elements are also permitted.

The systems disclosed herein may be packaged together in a single package. The finished package will be sterilized using sterilization methods such as ethylene oxide or radiation, and labeled and packaged in boxes. Instructions may also be provided within the package or via an internet link printed on the label.

P example

Example 1. A system for preparing an implant and inserting the implant endometrically into the eye of a patient, the system comprising: a tissue cassette configured to receive and hold a sheet of material; a cutting device; and a conveying device.

Embodiment 2. The system of embodiment 1, wherein the tissue cassette comprises a shaft extending from a distal end of the tissue cassette, at least a distal region of the shaft being sized and shaped for insertion into an anterior chamber of an eye, wherein the shaft comprises a lumen.

Embodiment 3. The system of embodiment 2, wherein the tissue cassette further comprises a base configured to receive the patch and a cover configured to hold the patch stationary against the base.

Embodiment 4. The system of embodiment 3, wherein the cutting device comprises a cutting member configured to cut pieces of material positioned within the tissue cassette.

Embodiment 5. The system of embodiment 4, wherein cutting the pieces of material with the cutting member forms an implant from the pieces, the implant configured to be implanted into an eye of a patient.

Embodiment 6. The system of embodiment 5, wherein the delivery device comprises an actuator configured to deploy the implant positioned within the cassette into the eye through the lumen of the shaft.

Example 7. A method of preparing an implant for implantation in an eye of a patient and inserting the implant into an eye of a patient, the method comprising: inserting a piece of material into a tissue cassette, the tissue cassette comprising a shaft extending from a distal end of the tissue cassette, at least a distal end region of the shaft being sized and shaped for insertion into an anterior chamber of an eye, wherein the shaft comprises a lumen; coupling a tissue cassette with a cutting device having a cutting member configured to cut pieces of material within the tissue cassette; cutting the blade with a cutting member to form an implant from the blade while the tissue cassette is coupled with the cutting device; separating the tissue cassette from the cutting device; coupling the tissue cassette to a delivery device; inserting a distal end region of the shaft into an anterior chamber of an eye; positioning the distal region adjacent to ocular tissue; and actuating the delivery device to deploy the implant from the cassette through at least a portion of the lumen such that the implant engages the ocular tissue.

Embodiment 8. The method of embodiment 7 further comprising delivering the viscous material through a shaft.

Example 9. A system for preparing an implant and inserting the implant endo-route into the eye of a patient, the system comprising: a tissue cassette configured to receive and hold a sheet of material; and a conveying device.

Embodiment 10. The system of embodiment 9, wherein the tissue cassette comprises a shaft extending from a distal end of the tissue cassette, at least a distal region of the shaft being sized and shaped for insertion into an anterior chamber of the eye, wherein the shaft comprises a lumen.

Embodiment 11. The system of embodiment 10, wherein the tissue cassette further comprises a base configured to receive the patch and a cover configured to hold the patch secured against the base.

Embodiment 12. The system of embodiment 11 further comprising a cutting device, wherein the cutting device comprises a cutting member configured to cut a piece of material positioned within the tissue cassette.

Embodiment 13. The system of embodiment 12, wherein cutting the pieces of material with the cutting member forms an implant from the pieces, the implant configured to be implanted into an eye of a patient.

Embodiment 14. The system of embodiment 13, wherein the delivery device comprises an actuator configured to deploy an implant positioned within at least a portion of the cartridge into the eye through the lumen of the shaft.

Embodiment 15. The system of embodiment 10 wherein the tissue cassette comprises a nose cone assembly comprising a distal region of the tissue cassette and a shaft, wherein the nose cone assembly is reversibly coupled to the tissue cassette and to the delivery device.

Embodiment 16. The system of embodiment 10 wherein the shaft of the tissue cassette is configured to deliver viscous material.

Example 17 a method of preparing an implant for implantation into an eye of a patient and inserting the implant into the eye of the patient, the method comprising: inserting a piece of material into a tissue cassette comprising a shaft extending from a distal end of the tissue cassette, at least a distal region of the shaft being sized and shaped for insertion into an anterior chamber of an eye, wherein the shaft comprises a lumen; coupling the tissue cassette with a cutting device having a cutting member configured to cut pieces of the material within the tissue cassette; cutting a piece with the cutting member to form an implant from the piece while the tissue cassette is coupled with the cutting device; separating at least a portion of the tissue cassette from the cutting device; coupling the at least a portion of the tissue cassette to a delivery device; inserting a distal region of the shaft into an anterior chamber of an eye; positioning the distal region adjacent to ocular tissue; and actuating the delivery device to deploy the implant from the cassette through at least a portion of the lumen such that the implant engages ocular tissue.

Embodiment 18 the method of embodiment 17, further comprising delivering the viscous material through a shaft.

Example 19 a system for preparing an implant from a sheet of material and inserting the implant internally into the eye of a patient, the system comprising: a tissue cassette comprising a nose cone and a distal shaft defining a lumen between the nose cone and a distal region of the distal shaft; a cutting device configured to be coupled to the nose cone; and a delivery device configured to be coupled to the nose cone.

Embodiment 20. The system of embodiment 19, wherein the distal region of at least the distal shaft is sized and shaped for insertion into the anterior chamber of an eye.

Embodiment 21. The system of embodiment 20 wherein the distal-most tip of the distal shaft is configured to dissect tissue for implantation in a supraciliary, schlemm's canal, or transscleral implant.

Embodiment 22. The system of embodiment 20, wherein the cutting device comprises a base configured to receive the tile.

Embodiment 23 the system of embodiment 22, wherein the cutting device comprises a cutting member configured to cut the pieces of material into the implant.

Embodiment 24. The system of embodiment 23, wherein the cutting device further comprises a compression tool configured to push the implant into the lumen of the distal shaft.

Embodiment 25 the system of embodiment 24, wherein the delivery device comprises an actuator configured to deploy the implant compressed within the lumen of the distal shaft into the eye.

The system of P embodiment 26, further comprising a movable inner elongate member operatively coupled to the actuator to advance the implant through the lumen and out the distal opening of the distal shaft.

Example 27. A method of preparing an implant for implantation in an eye of a patient from a sheet of material and inserting the implant into an eye of a patient, the method comprising: coupling a tissue cassette with a cutting device, the tissue cassette comprising a shaft extending from a distal end of the tissue cassette, at least a distal end region of the shaft sized and shaped for insertion into an anterior chamber of an eye, wherein the shaft comprises a lumen, the cutting device having a cutting member configured to cut pieces of material; cutting the pieces with a cutting member to form an implant from the pieces; compressing the implant within the shaft lumen; separating the tissue cassette from the cutting device; coupling the tissue cassette to a delivery device; inserting the distal end region of the shaft into the anterior chamber of the eye; positioning the distal region adjacent to ocular tissue; and actuating the delivery device to deploy the implant from the lumen such that the implant engages the ocular tissue.

P embodiment 28 the method of P embodiment 27, further comprising delivering the viscous material through a shaft.

Example 29 a system for preparing an implant and inserting the implant endometrically into an eye of a patient, the system comprising: a tissue cassette; and a conveying device.

The system of P embodiment 30, wherein the tissue cassette comprises a shaft extending from a distal end of the tissue cassette, at least a distal region of the shaft sized and shaped for insertion into an anterior chamber of an eye, wherein the shaft comprises a lumen.

Embodiment 31 the system of embodiment 30 further comprising a cutting device, wherein the cutting device comprises a cutting member configured to cut the pieces of material.

The system of P embodiment 32, wherein cutting the pieces of material with the cutting member forms an implant from the pieces, the implant configured to be implanted into an eye of a patient.

Embodiment 33. The system of embodiment 32, wherein the delivery device comprises an actuator configured to deploy an implant positioned within the shaft into the eye through the lumen of the shaft.

The system of P embodiment 34, wherein the tissue cassette comprises a nose cone assembly comprising a distal region of the tissue cassette and a shaft, wherein the nose cone assembly is reversibly coupled to the tissue cassette and to the delivery device.

P embodiment 35. The system of P embodiment 30, wherein the shaft of the tissue cassette is configured to deliver viscous material.

Example 36. A method of preparing an implant for implantation into an eye of a patient and inserting the implant into the eye of the patient, the method comprising: cutting the pieces of material with a cutting member of a cutting device to form implants from the pieces; compressing the implant within a lumen of a shaft extending from a distal end of the tissue cassette; separating at least a portion of the tissue cassette from the cutting device; coupling at least a portion of the tissue cassette to a delivery device; inserting the distal end region of the shaft into the anterior chamber of the eye; positioning the distal region adjacent to ocular tissue; and actuating the delivery device to deploy the implant from the tissue cassette through at least a portion of the lumen such that the implant engages the ocular tissue.

Embodiment 37 the method of embodiment 36, further comprising delivering the viscous material through a shaft.

Example 38. A method of treating an eye with minimally modified biological tissue.

Embodiment 39. The method of embodiment 38, wherein the biological tissue is scleral tissue, and minimally modifying the scleral tissue comprises compressing the scleral tissue within the distal shaft from a first size to a second, smaller size.

Example 40. The method of example 39, wherein the distal shaft is sized and shaped for insertion into the anterior chamber through a self-sealing incision in the cornea of the eye.

Embodiment 41 the method of embodiment 40, further comprising deploying compressed scleral tissue from the distal shaft between the tissue layers near the iridocorneal angle.

P embodiment 42. The method of P embodiment 41, wherein the compressed scleral tissue deployed from the distal shaft is restored to the first size.

Example 43 the method of example 42, further comprising treating glaucoma with compressed scleral tissue.

The method of P embodiment 44, wherein deploying compressed scleral tissue from the distal shaft between tissue layers near the iridocorneal angle comprises deploying the compressed scleral tissue at least partially within schlemm's canal and at least partially within the anterior chamber, or at least partially between the ciliary body and the sclera of the eye, or at least partially within a ciliary separation procedure split.

Embodiment 45. The method of embodiment 41, wherein deploying compressed scleral tissue from the distal shaft between the tissue layers near the iridocorneal angle comprises deploying the compressed scleral tissue within the ciliary separation tear such that a proximal end of the compressed scleral tissue is prevented from protruding within the anterior chamber.

Embodiment 46. The method of embodiment 41, wherein deploying compressed scleral tissue from the distal shaft between the tissue layers near the iridocorneal angle comprises retracting the distal shaft while maintaining the position of the compressed scleral tissue relative to the tissue layers.

Embodiment 47. The method of embodiment 41, wherein deploying compressed scleral tissue from the distal shaft between the tissue layers near the iridocorneal angle comprises pushing the compressed scleral tissue out of the distal shaft and into position between the tissue layers.

Embodiment 48. A system for deploying an implant cut from biological tissue into an eye of a patient, the system comprising: a transfer device, the transfer device comprising: a proximal handle; at least one actuator; and a distal coupler; and a nose cone assembly, the nose cone assembly comprising: a nose cone having a proximal region and a distal region; a coupler on the proximal region of the nose cone, the coupler configured to reversibly engage with a distal coupler of the delivery device; and a tubular shaft protruding from a distal region of the nose cone, the tubular shaft comprising one or more fenestrations covered by a translucent or transparent material to reveal a lumen of the tubular shaft.

Embodiment 49. The system of embodiment 48, wherein the one or more fenestrations form a metering system of the tubular shaft configured to identify a depth of insertion of the tubular shaft and/or a length of the implant within the lumen.

The system of P embodiment 50, wherein the tubular shaft comprises an introduction tube formed of an opaque material and an outer tube formed of a translucent or transparent material.

The system of P embodiment 51, wherein the tubular shaft comprises a distal region distal to the one or more fenestrations.

The system of P embodiment 52, wherein the distal region is curved away from the longitudinal axis of the proximal region of the tubular shaft such that the distal opening from the lumen surrounds an axis different from the longitudinal axis of the proximal region.

P embodiment 53 the system of P embodiment 51, wherein the distal region is formed of a translucent or transparent material.

Example 54. The system of example 51, wherein the biological tissue is the sclera or cornea.

P embodiment 55. A trephine device for minimal modification of biologically derived tissue, the device configured to cut the biologically derived tissue into elongated tissue strips having a length and a width, wherein the length is greater than the width.

P embodiment 56 the device of P embodiment 55, wherein the tissue strip is for implantation into an eye of a patient.

P embodiment 57. The device of P embodiment 55, wherein the width is less than about 3mm and the length is greater than about 3mm.

Embodiment 58 the device of embodiment 55, wherein the biologically-derived tissue comprises scleral tissue or corneal tissue harvested from the donor or patient.

The device of P embodiment 59, further comprising at least one sharp edge configured to cut the biologically-derived tissue to the width.

Claims

1. A system for deploying an implant cut from biological tissue into an eye of a patient, the system comprising:

A transfer device, the transfer device comprising:

A proximal housing;

At least one actuator; and

A distal coupler; and

A nose cone assembly, the nose cone assembly comprising:

A nose cone having a proximal region and a distal region;

a coupler on the proximal end region of the nose cone configured to reversibly engage with the distal coupler of the delivery device; and

A tubular shaft protruding from the distal region of the nose cone and comprising a lumen, the tubular shaft comprising one or more fenestrations extending through a sidewall of the shaft, the one or more fenestrations being covered by a translucent or transparent material so as to reveal the lumen of the tubular shaft.

2. The system of claim 1, wherein the one or more fenestrations form a metering system of the tubular shaft configured to identify a depth of insertion of the tubular shaft and/or a length of the implant within the lumen.

3. The system of claim 1, wherein the tubular shaft comprises an introduction tube and an outer tube, the introduction tube being formed of an opaque material and the outer tube being formed of the translucent or transparent material.

4. The system of claim 1, wherein the tubular shaft comprises a distal region distal to the one or more fenestrations.

5. The system of claim 4, wherein the distal region is curved away from a longitudinal axis of a proximal region of the tubular shaft such that a distal opening from the lumen surrounds an axis different from the longitudinal axis of the proximal region.

6. The system of claim 4, wherein the distal region is formed of a translucent or transparent material.

7. The system of claim 1, further comprising the implant.

8. The system of claim 7, wherein the biological tissue of the implant is scleral or corneal biological tissue.

9. A device for minimal modification of biologically derived tissue, the device comprising two blades separated by a gap, each blade having an inner face and at least one distal bevel forming a cutting edge, wherein the two blades are mounted at an angle relative to each other such that the inner faces are non-parallel and the distal bevels are parallel to each other, wherein the device is configured to cut the biologically derived tissue into an elongated strip having a length and a width, wherein the length is greater than the width.

10. The device of claim 9, wherein the distal bevel is orthogonal to the tissue.

11. The device of claim 9, wherein the strap is configured to be implanted in an eye of a patient.

12. The device of claim 9, wherein the width is less than about 3mm and the length is greater than about 3mm.

13. The device of claim 9, wherein the biologically derived tissue comprises scleral tissue or corneal tissue harvested from a donor or patient.

14. A cassette for use with a system for preparing an implant and inserting the implant endometrically into an eye, the cassette comprising:

a lower component having a planar upper surface sized and shaped to receive a piece of material to be cut into an implant;

An upper member movably coupled to the lower member between an open configuration and a closed configuration, the upper member having a lower surface arranged to oppose the upper surface of the lower member when the upper member is in the closed configuration; and

A pair of blades configured to extend below a lower surface of the upper member to cut a piece of the material into the implant.

15. The cartridge of claim 14, wherein the piece of material remains fixed relative to the lower member when the upper member is in the closed configuration.

16. The cartridge of claim 14, further comprising an actuator configured to cause the pair of blades to cut the pieces of material into the implant.

17. The cartridge of claim 16, wherein the actuator comprises a lever configured to move the pair of blades relative to the upper surface.

18. The cartridge of claim 14, wherein the actuator comprises a handle having a first handle portion and a second handle portion coupled in a scissor arrangement by a hinge.

19. The cartridge of claim 18, wherein the lower member includes a first aperture extending therethrough sized and shaped to receive the distal protrusion of the first handle portion, and the upper member includes a second aperture extending therethrough sized and shaped to receive the distal protrusion of the second handle portion.

20. The cartridge of claim 19, wherein the apertures of the upper and lower members are each shaped to prevent rotation relative to the distal projections of the first and second handle portions.

21. The cartridge of claim 19, wherein the aperture and the distal protrusion are coupled by a slip fit or an interference fit.

22. The cartridge of claim 19, wherein expanding the first and second handle portions expands the lower and upper members from the closed configuration toward the open configuration.

23. The cartridge of claim 14, wherein the pair of blades are separated by a gap, and wherein each blade of the pair of blades has an inner face and at least one distal bevel forming a cutting edge, wherein the pair of blades are mounted at an angle relative to each other such that the inner faces are not parallel and the distal bevels are parallel to each other.

24. The cartridge of claim 23, wherein the distal ramp is orthogonal to the upper surface.

25. The cassette of claim 14, wherein the implant is an elongated strip having a length and a width, wherein the length is greater than the width.

26. A system for preparing an implant for implantation in an eye of a patient and inserting the implant into an eye of a patient, the system comprising:

a cassette configured to receive a piece of material and comprising a pair of blades configured to cut the piece to form an implant from the piece; and

A delivery instrument comprising a housing and a distal portion sized and shaped for insertion into an anterior chamber of an eye, wherein the distal portion comprises a lumen having an elongate tubular member sized to receive the implant cut from the segment with the pair of blades.

27. The system of claim 26, further comprising an actuator configured to cause the pair of blades to cut the pieces of material into the implant.

28. The system of claim 27, wherein the actuator comprises a rod configured to move the pair of blades relative to the tile.

29. The system of claim 27, wherein the actuator comprises a handle having a first handle portion and a second handle portion coupled in a scissor arrangement by a hinge.

30. The system of claim 29, wherein the cartridge comprises a lower member having an upper surface and an upper member having a lower surface, the pair of blades extending below the lower surface of the upper member.

31. The system of claim 30, wherein the lower member includes a first aperture extending therethrough sized and shaped to receive a distal protrusion of the first handle portion, and the upper member includes a second aperture extending therethrough sized and shaped to receive a distal protrusion of the second handle portion.

32. The system of claim 31, wherein the first and second apertures of the upper and lower members are each shaped to prevent rotation relative to distal protrusions of the first and second handle portions.

33. The system of claim 31, wherein the first and second holes and the distal protrusion are coupled by a slip fit or an interference fit.

34. The system of claim 30, wherein expanding the first and second handle portions expands the lower and upper members from a closed configuration toward an open configuration.

35. The system of claim 26, wherein the pair of blades are separated by a gap, and wherein each blade of the pair of blades has an inner face and at least one distal bevel forming a cutting edge, wherein the pair of blades are mounted at an angle relative to each other such that the inner faces are not parallel and the distal bevels are parallel to each other.

36. The system of claim 35, wherein the distal bevel is orthogonal to the tile.

37. The system of claim 26, wherein the implant is an elongated strip having a length and a width, wherein the length is greater than the width.

38. The system of claim 26, wherein the elongate tubular member comprises one or more fenestrations extending through a sidewall of the tubular member.

39. The system of claim 38, wherein the one or more fenestrations are covered by a translucent or transparent material so as to reveal the lumen of the tubular member.

40. The system of claim 38, wherein the one or more fenestrations form a metering system of the tubular member configured to identify a depth of insertion of the tubular member and/or a length of the implant within the lumen.

41. The system of claim 38, wherein the tubular member comprises an introduction tube and an outer tube, the introduction tube being formed of an opaque material and the outer tube being formed of a translucent or transparent material.

42. The system of claim 38, wherein the tubular member comprises a distal region distal to the one or more fenestrations.

43. The system of claim 42, wherein the distal region is curved away from a longitudinal axis of the proximal region of the tubular member such that a distal opening from the lumen surrounds an axis different from the longitudinal axis of the proximal region.

44. The system of claim 42, wherein the distal region is formed of a translucent or transparent material.

45. The system of claim 26, wherein the material comprises a bio-derived material suitable for implantation in an eye.

46. The system of claim 45, wherein the biologically derived material comprises tissue, allograft material or xenograft material harvested from a donor or from a patient.

47. The system of claim 26, wherein the material comprises an engineered material or a 3D printed material suitable for implantation in an eye.

48. The system of claim 26, wherein the implant comprises one or more therapeutic agents.

49. The system of claim 26, wherein the distal region of the elongate tubular member is at least one of angled or curved or flexible.

50. The system of claim 26, wherein the lumen comprises a circular cross-section.

51. The system of claim 26, further comprising an actuator on the housing configured to retract the elongate tubular member from the implant while maintaining implant position relative to adjacent ocular tissue.

52. The system of claim 51, further comprising an inner elongate member configured to contact a proximal end of the implant when the elongate tubular member is retracted by the actuator.

53. The system of claim 51, wherein the actuator on the housing comprises at least one of a dial, a slider, or a button.

54. The system of claim 26, wherein the distal-most end of the elongate tubular member is blunt to allow dissection of ocular tissue without cutting ocular tissue.

55. A system for preparing an implant for implantation in an eye of a patient and inserting the implant into an eye of a patient, the system comprising:

a cartridge configured to contain and retain material within the cartridge;

at least one cutting member configured to cut the material to form an implant from the material; and

A delivery instrument comprising a housing and a distal portion sized and shaped for insertion into an anterior chamber of an eye, wherein the distal portion comprises a lumen having an elongate tubular member.

56. The system of claim 55, wherein a distal-most end of the elongate tubular member is configured to dissect tissue for implantation in schlemm's canal or transscleral implantation.

57. The system of claim 55, wherein the housing further comprises a movable inner elongate member configured to advance the implant through the lumen and out of the distal opening of the elongate tubular member.

58. The system of claim 55, further comprising an actuator configured to cause the at least one cutting member to cut the material to form the implant.

59. The system of claim 58, wherein the actuator comprises a rod configured to move the at least one cutting member relative to the material.

60. The system of claim 58, wherein the actuator comprises a handle having a first handle portion and a second handle portion coupled in a scissor arrangement by a hinge.

61. The system of claim 60, wherein the cartridge comprises a lower component having an upper surface and an upper component having a lower surface, the at least one cutting member comprising a pair of blades extending below the lower surface of the upper component.

62. The system of claim 61, wherein the lower member includes a first aperture extending therethrough sized and shaped to receive the distal protrusion of the first handle portion, and the upper member includes a second aperture extending therethrough sized and shaped to receive the distal protrusion of the second handle portion.

63. The system of claim 62, wherein the first and second apertures of the upper and lower members are each shaped to prevent rotation relative to distal protrusions of the first and second handle portions.

64. The system of claim 62, wherein the first and second apertures and the distal protrusion are coupled by a slip fit or an interference fit.

65. The system of claim 61, wherein expanding the first and second handle portions expands the lower and upper members from a closed configuration toward an open configuration.

66. The system of claim 55, wherein the at least one cutting member comprises a pair of blades separated by a gap, and wherein each blade of the pair of blades has an inner face and at least one distal bevel forming a cutting edge, wherein the pair of blades are mounted at an angle relative to each other such that the inner faces are not parallel and the distal bevels are parallel to each other.

67. The system of claim 66, wherein the distal bevel is orthogonal to the material.

68. The system of claim 55, wherein the implant is an elongated strip having a length and a width, wherein the length is greater than the width.

69. The system of claim 55, wherein the elongate tubular member comprises one or more fenestrations extending through a sidewall of the tubular member.

70. The system of claim 69, wherein the one or more fenestrations are covered by a translucent or transparent material to reveal the lumen of the tubular member.

71. The system of claim 69, wherein the one or more fenestrations form a metering system of the tubular member configured to identify a depth of insertion of the tubular member and/or a length of the implant within the lumen.

72. The system of claim 69, wherein the tubular member comprises an introduction tube and an outer tube, the introduction tube being formed of an opaque material and the outer tube being formed of a translucent or transparent material.

73. The system of claim 69, wherein the tubular member comprises a distal region distal to the one or more fenestrations.

74. The system of claim 73, wherein the distal region is curved away from a longitudinal axis of the proximal region of the tubular member such that a distal opening from the lumen surrounds an axis different from the longitudinal axis of the proximal region.

75. The system of claim 73, wherein the distal region is formed of a translucent or transparent material.

76. A system for preparing an implant and inserting the implant endometrically into an eye, the system comprising:

A blade cartridge configured to move between an open configuration and a closed configuration for loading a piece of material into the blade cartridge, the cartridge comprising:

a lower component having an upper surface configured to receive a piece of the material;

An upper member having a lower surface configured to abut against a patch of the material when the cartridge is in a closed configuration; and

A pair of blades and a spacer defining a gap between the blades,

Wherein the pair of blades are configured to extend below the lower surface of the upper member to penetrate the piece of material at two locations to form a strip of the material having a width that is narrower than a width of the piece of material when the blade cartridge is moved to a closed configuration.

77. The system of claim 76, wherein the upper member and the lower member are hinged relative to one another.

78. The system of claim 76, wherein the upper member and the lower member are reversibly coupled to each other.

79. The system of claim 76, wherein the gap defined by the spacer determines a width of the strip.

80. The system of claim 76, wherein each blade of the pair of blades comprises a single bevel edge or a double bevel edge.

81. The system of claim 76, further comprising an actuator configured to cause the pair of blades to cut the piece to form the strip.

82. The system of claim 81, wherein the actuator comprises a rod configured to move the pair of blades relative to the upper surface.

83. The system of claim 81, wherein the actuator comprises a handle having a first handle portion and a second handle portion coupled in a scissor arrangement by a hinge.

84. The system of claim 83, wherein the lower member includes a first aperture extending therethrough sized and shaped to receive the distal protrusion of the first handle portion, and the upper member includes a second aperture extending therethrough sized and shaped to receive the distal protrusion of the second handle portion.

85. The system of claim 84, wherein the first and second apertures of the upper and lower members are each shaped to prevent rotation relative to distal projections of the first and second handle portions.

86. The system of claim 84, wherein the first and second apertures and the distal protrusion are coupled by a slip fit or an interference fit.

87. The system of claim 84, wherein expanding the first and second handle portions expands the lower and upper members from a closed configuration toward an open configuration.

88. The system of claim 76, wherein each blade of the pair of blades has an inner face and at least one distal bevel forming a cutting edge, wherein the pair of blades are mounted at an angle relative to each other such that the inner faces are not parallel and the distal bevels are parallel to each other.

89. The system of claim 88, wherein the distal bevel is orthogonal to the upper surface.

90. The system of claim 76, further comprising the piece of material.

91. The system of claim 76, wherein the material comprises a bio-derived material suitable for implantation into an eye.

92. The system of claim 91, wherein the biologically-derived material comprises tissue harvested from a donor or from an eye.

93. The system of claim 91, wherein the biologically derived material is an autograft material, an allograft material, or a xenograft material.

94. The system of claim 76, wherein the material is an engineering organization.

95. The system of claim 94, wherein the engineered tissue is a 3D printed material suitable for implantation.

96. The system of claim 76, wherein the implant comprises one or more therapeutic agents.

97. The system of claim 76, further comprising a conveyor, the conveyor comprising:

A proximal housing having one or more actuators;

An inner pusher; and

An outer tube including an inner lumen sized to receive the inner pusher.

98. The system of claim 97, wherein the inner pusher is configured to be advanced distally using the one or more actuators of the proximal housing of the delivery device.

99. The system of claim 97, wherein the lumen of the outer tube is sized to receive the width of the strip.

100. The system of claim 97, wherein the outer tube is configured to inject a viscoelastic material using the inner pusher as a plunger.

101. The system of claim 97, wherein at least a proximal portion of the outer tube extends along a longitudinal axis, and wherein a distal region of the outer tube is angled away from the longitudinal axis.

102. The system of claim 97, wherein the distal-most end of the outer tube is blunt to allow dissection between tissue of an eye without cutting the tissue.

103. The system of claim 97, wherein the outer tube includes one or more fenestrations extending through a sidewall of the outer tube.

104. The system of claim 103, wherein the one or more fenestrations are covered by a translucent or transparent material to reveal the lumen of the outer tube.

105. The system of claim 103, wherein the one or more fenestrations form a metering system of the outer tube configured to identify a depth of insertion of the outer tube and/or a length of the implant within the lumen.

106. The system of claim 103, wherein the outer tube comprises an introduction tube formed of an opaque material and an outer tubular member formed of a translucent or transparent material.

107. The system of claim 103, wherein the outer tube comprises a distal region distal to the one or more fenestrations.

108. The system of claim 107, wherein the distal region is curved away from a longitudinal axis of a proximal region of the outer tube such that a distal opening from the lumen surrounds an axis different from the longitudinal axis of the proximal region.

109. The system of claim 107, wherein the distal region is formed of a translucent or transparent material.

110. The system of claim 97, wherein a distal region of the outer tube has a maximum outer diameter of no greater than about 1.3 mm.

111. The system of claim 97, wherein the outer tube is a hypotube having an inner diameter of less than about 0.036 "to about 0.009".

112. The system of claim 97, wherein the outer tube is coupled to a first actuator of the one or more actuators and the inner pusher is coupled to a second actuator.

113. The system of claim 97, wherein distal advancement of the inner pusher pushes the implant distally through the lumen of the outer tube into a ready position proximate to a distal opening from the lumen of the outer tube.

114. The system of claim 113, wherein proximal retraction of the outer tube withdraws the implant for deployment into an eye while the inner pusher remains stationary relative to the housing.

115. A system for deploying an implant cut from biological tissue into an eye of a patient, the system comprising:

A transfer device, the transfer device comprising:

A proximal housing;

At least one actuator coupled to the pushrod; and

A distal coupler; and

A nose cone assembly, the nose cone assembly comprising:

A nose cone having a proximal region and a distal region;

A tubular shaft protruding from the distal region of the nose cone and comprising a lumen, the tubular shaft comprising a distal region and a proximal region, wherein the distal region is curved away from a longitudinal axis of the proximal region.

116. The system of claim 115, wherein the distal region forms a tangential arc having a radius between 10-20 mm.

117. The system of claim 115, wherein the distal region is beveled such that an opening from the lumen is elongated and a distal-most tip of the shaft extends beyond the opening.

118. The system of claim 115, wherein the distal region has a bevel.

119. The system of claim 118, wherein the bevel is about 10-45 degrees.

120. The system of claim 118, wherein the opening near the proximal heel of the bevel is circular and the opening near the distal-most end of the shaft is square.

121. The system of claim 115, wherein the pushrod is sized to extend through the lumen of the shaft to the opening.

122. The system of claim 115, wherein the pushrod is formed from nitinol or stainless steel.

123. The system of claim 115, wherein the pushrod is a monofilament or a braided member.

124. The system of claim 115, wherein the pushrod is a completely cylindrical element without an inner lumen.

125. The system of claim 115, wherein the pushrod has a proximal region, a distal region, and an intermediate region between the proximal region and the distal region.

126. The system of claim 125, wherein the intermediate region has greater flexibility than the proximal region.

127. The system of claim 126, wherein the greater flexibility of the intermediate region is configured to translate through a curved distal region of the shaft.

128. The system of claim 125, wherein an outer diameter of the pushrod varies from a proximal region of the pushrod to a distal region of the pushrod.

129. The system of claim 125, wherein an outer diameter of the distal region is greater than an outer diameter of the intermediate region.

130. The system of claim 129, wherein the outer diameter of the distal region is 0.525mm-0.575mm.

131. The system of claim 130, wherein the intermediate region has an outer diameter of 0.200mm-0.300mm.

132. The system of claim 131, wherein the lumen of the shaft has an inner diameter of 0.600mm-0.900 mm.

133. The system of claim 125, wherein the intermediate region has a length of about 8-10 mm.

134. The system of claim 125, wherein the distal region of the pushrod has a length of about 2mm-5 mm.

135. The system of claim 115, wherein the at least one actuator comprises a second actuator and a first actuator configured to slide within a slider track of the housing.

136. The system of claim 135, wherein the first actuator comprises an outer portion positioned outside the housing and an inner portion positioned inside the housing.

137. The system of claim 136, wherein the inner portion comprises a flexing portion having protrusions, the flexing portion being movable between a compressed position and a relaxed configuration.

138. The system of claim 137, wherein the proximal housing has a backstop positioned below a slider track of the housing.

139. The system of claim 138, the protrusion engaging the backstop when the flexure is in a relaxed configuration, thereby preventing proximal movement of the first actuator relative to the housing.

140. The system of claim 115, wherein the tubular shaft comprises one or more fenestrations extending through a sidewall of the shaft, the one or more fenestrations covered by a translucent or transparent material to reveal the lumen of the tubular shaft.

141. The system of claim 140, wherein the one or more fenestrations form a metering system of the tubular shaft configured to identify a depth of insertion of the tubular shaft and/or a length of the implant within the lumen.

142. The system of claim 115, wherein the tubular shaft comprises an introduction tube and an outer tube, the introduction tube being formed of an opaque material and the outer tube being formed of a translucent or transparent material.

143. The system of claim 115, wherein the distal region is formed of a translucent or transparent material.