JP2023103247A - Tools and instruments for use with implantable encapsulation devices - Google Patents

Abstract

To provide tools and instruments for holding, transferring, delivering and deploying an implantable device, and methods and means of aseptically storing and shipping the implantable device.SOLUTION: Embodiments include, but are not limited to, a device case for protecting, housing and filling a device, a surgical sizer for preparing an implantable site, and a deployer for transferring the implantable device from the device case and delivering or deploying the implantable device to the prepared implantable site.SELECTED DRAWING: Figure 6

Description

STATEMENT OF FEDERAL SUPPORT This study was funded in part by the California Institute for Regenerative Medicine (Grant No. DR1-01423).
made possible with a grant from The responsibility for the content of this publication lies solely with the inventors, and the content is
It does not necessarily represent the official views of CIRM or any other agency of the State of California.

(1. Field of the Invention)
The present invention relates generally to cell therapy, and to means and methods for holding, transporting, sizing, marking and placing cell-encapsulated implantable devices for the treatment of human disease, particularly diabetes.

(2. Description of related technology)
Cell replacement therapy for some diseases can be a therapeutic treatment by transferring cells, tissues or organs to a patient with that particular disease. Commercial cell therapy remains a major challenge of renewable cell sources and encapsulation sources that provide allo-protection against host immunity. Ideally, such an implantable device would minimize or eliminate the patient's long-term use of immunosuppressive drugs.

Previously, Applicants have described both renewable cell sources and macroencapsulated drug delivery systems that are at least suitable for the purpose of delivering pancreatic progenitor cells to produce insulin in response to glucose stimulation in vivo.
For example, at least U.S. patent application Ser.
NES, U.S. patent application Ser. No. 12/618,659, filed November 13, 2009, entitled E
NCAPSULATION OF PANCREATIC LINEAGE CELLS
DERIVED FROM HUMAN PLURIPOTENT STEM CEL
LS, U.S. patent application Ser. No. 14/106,330, filed Dec. 12, 2013, entitled IN
VITRO DIFFERENTIATION OF PLURIPOTENT ST
EM CELLS TO PANCREATIC ENDODERM CELLS (PE
C) AND IMMATURE BETA CELLS, U.S. Patent Application Serial No. 14/201,630 filed March 7, 2014 and PCT/U filed March 13, 2014
S2014/026529, IN VITRO DIFFERENTIATION OF
PLURIPOTENT STEM CELLS TO PANCREATIC EN
DODERM CELLS (PEC) AND ENDOCRINE CELLS, 201
PCT/US2014/022109 filed Mar. 4, 2014, 3-DIMENSIONAL
LARGE CAPACITY CELL ENCAPSULATION DEVIC
E, and U.S. Design Application No. 29/408,366, filed Dec. 12, 2011;
U.S. Design Application No. 29/408,368 filed December 12, 2011; U.S. Design Application No. 29/423,365 filed May 31, 2012; U.S. Design Application No. 29/447,944 filed March 13, 2013;
84,363, U.S. Design Application No. 29/484,359, U.S. Design Application No. 29/484
, 360, U.S. Design Application No. 29/484,357, U.S. Design Application No. 29/484,3.
56, U.S. Design Application No. 29/484,355, U.S. Design Application No. 29/484,362
and U.S. Design Application No. 29/484,35, Title 3-DIMENSIONAL LA
See RGE CAPACITY CELL ENCAPSULATION DEVICE.

Such encapsulated cell products ("combined products") for the treatment of diabetes
ation product) is not commercially available. The commercially available combination product includes systems and methods for ensuring and maintaining the integrity of the implantable device within its own case, sterilizing the implantable device and case, aseptically filling the implantable device with live cells, storing and transporting the combination product to the clinical site, preparing the anatomical implantation site by sizing, marking the anatomical implantation site,
An assembly must then be provided for holding, transporting and placing the combination product at its anatomical implantation site.

Provided herein is a method of deploying an implantable device for cell therapy, comprising the steps of positioning an assembly comprising an implantable device and a holder having first and second plates and a deployer plate at an anatomical implantation site, comprising:
The second holder further includes a rod and a handle, the deployer element being coupled to the rod and movable along the axis of the rod, the step and the rod and the first and second
moving the deployer element relative to the holder of the anatomical implantation site to thereby deploy or deliver the implantable device to the anatomical implantation site;
A method is disclosed. Further, an assembly for deploying an implantable device, comprising a first holder, a second holder comprising a rod or shaft and a handle, and a deployer mechanism between the first and second holders, the deployer mechanism adapted to effect deployment of the implantable device, the first holder and the deployer mechanism being removably coupled to the second holder rod and movable along the longitudinal axis of the rod, movement of the deployer mechanism relative to the first and second holders. discloses an assembly in which an implantable device is delivered or deployed. Further disclosed is a case for holding an implantable two-dimensional shaped device, the case including a cover body and a base body that are removably coupled, the cover body having a first latching portion, the base body having a second latching portion configured to secure the cover body to the base body when the case is in a closed position, the cover body and the base body including a volume having at least one opening that, when secured, allows passage of one or more bioactive agents. Further embodiments are disclosed.

The above and other features and advantages of the present invention will become apparent from the following more specific description of preferred embodiments of the invention, the accompanying drawings, and the claims.

For a more complete understanding of embodiments of the present invention and its advantages, reference should now be made to the following description taken in conjunction with the accompanying drawings briefly described below.

1 is an exploded perspective view of a device case showing component parts and an implantable device according to one embodiment of the present invention; FIG.

2 is a perspective view of an open device case of the present invention, as shown in FIG. 1, having a base body and a cover body, hingedly attachable and containing an implantable device including a port therein; FIG.

3 is a perspective view of a closed device case of the present invention, as shown in FIG. 1, having a base body and a cover body, hingedly attachable and containing an implantable device including a port therein; FIG.

4A-4E are perspective views of finger grip structures according to embodiments of the present invention.

FIG. 5 is a top view of the window structure in the cover body and base body of the device case according to one embodiment of the present invention.

FIG. 6 is a perspective view of a device case and device filling pouch assembly (DFPA) for containing and sterilizing an implantable device therein, according to one embodiment of the present invention;

Figure 7 is a perspective view of a device case reservoir according to one embodiment of the present invention;

8 is an exploded perspective view of the device case storage container and components of FIG. 7 for inserting the device case and implantable device therein, with the coversheet of the container removed for clarity of the drawing, according to one embodiment of the present invention.

FIG. 9 is a perspective view of a device case storage container with an implantable device case and an implantable device therein, with the coversheet of the container removed for clarity of drawing, according to one embodiment of the present invention;

FIG. 10 is a perspective view of a device case storage container shipping bag with the container coversheet removed for clarity of drawing, according to one embodiment of the present invention.

FIG. 11 is a perspective view of a device case storage container shipping bag with a device case storage container therein, with the cover sheet of the container removed for clarity of the drawing, according to one embodiment of the present invention.

12A-12B are perspective views of a surgical sizer external and internal to an implantation site, according to one embodiment of the present invention.

FIG. 13A is an exploded perspective view of a sequence of use of an implantable device deployer, according to one embodiment of the present invention. Figure 13B is an exploded perspective view of the order of use of the implantable device deployer showing the component parts, according to one embodiment of the present invention. FIG. 13C is an exploded perspective view of the sequence of use of an implantable device deployer during transfer of the implantable device from the device case, according to one embodiment of the present invention. FIG. 13D is an exploded perspective view of the sequence of use of the implantable device deployer during transfer of the implantable device from the device case, according to one embodiment of the present invention. FIG. 13E is an exploded perspective view of the sequence of use of an implantable device deployer during transfer of the implantable device from the device case, according to one embodiment of the present invention. Figure 13F is an exploded perspective sequence of use view showing delivery and placement of an implantable device at an implantation site, according to one embodiment of the present invention. FIG. 13G is an exploded perspective sequence of use view showing delivery and placement of an implantable device at an implantation site, according to one embodiment of the present invention. FIG. 13H is an exploded perspective sequence of use view showing delivery and placement of an implantable device at an implantation site, according to one embodiment of the present invention. FIG. 13I is a cross-sectional view of the shaft of the deployer, according to one embodiment of the invention.

Figure 14A is a perspective view of an alternative implantable device deployer embodiment, according to one embodiment of the present invention. Figure 14B is an exploded perspective view of an implantable device deployer showing the component parts of the implantable device deployer, according to one embodiment of the present invention. FIG. 14C is a view after delivery and placement of the implantable device at the anatomical implantation site, according to one embodiment of the invention.

(Detailed description of embodiments)
Further features and advantages of the present invention, as well as the structure and operation of various embodiments of the present invention, are described in detail below with reference to accompanying FIGS. In the drawings, the same reference numbers refer to the same elements. Although embodiments of the present invention are described in the context of an implanted device containing pancreatic progenitor cells for the treatment of diabetes, it will be appreciated by those skilled in the art that the present invention may be applied to (but not limited to) thyroid cells, parathyroid cells, pancreatic cells, enterocytes, thymocytes, hepatocytes, endocrine cells, skin cells, hematopoietic cells, bone marrow stem cells, kidney cells, muscle cells, nerve cells, stem cells, ES cells,
lineage-restricted cells, progenitor cells, precursor cells, genetically modified cells, tumor cells, and (
It will be readily appreciated that it is applicable for macroencapsulation of any type of biological cell, therapeutic agent or mixture thereof, including derivatives and combinations thereof for the treatment of one or more diseases or conditions, including but not limited to diabetes. Also, cell-based products such as proteins (eg, hormones and/or other proteins that are deficient in human disease), antibodies, antibiotics, lymphokines, and the like for therapeutic indications.
Also contemplated are cells that produce a base product. Those skilled in the art will also appreciate that the present invention is applicable to a variety of implantable device types, materials, sizes and/or configurations.

Reference is made herein to various publications, including scientific journal articles, patent publications and patents, the disclosures of each of which are incorporated herein by reference in their entirety. for example,
Methods of producing insulin-secreting cells and implantation of implantable devices containing human multifunctional stem cell-derived pancreatic progenitors for the production of insulin-secreting cells are described in Applicants' U.S. Pat.
, 920, U.S. Pat. No. 8,338,170, U.S. Pat. No. 8,278,106, and U.S. Pat. No. 8,425,928, which are incorporated herein by reference in their entirety.

(device case)
1-4 illustrate non-limiting and non-exclusive embodiments of Case 1 for ensuring and maintaining the integrity of implantable devices. Cases are defined as “implantable device case”, “
Also referred to as a device case,” “cage,” “case,” or equivalents thereof. For example, in one embodiment, the device case is sterilized when the implantable device is sterilized or sterilizable (e.g., autoclave resistant), transported, filled, etc.
Maintain the integrity of implantable devices. The case is generally case 1 and the first
a portion (e.g. lid, cover, cover body, top body) 10, a second portion (e.g. bottom, base, tray, base tray, receptacle body) 30 and a third portion (e.g.
windows, openings, partitions, sections) 20, a fourth portion (graspable means, e.g. finger grips, handles, sidewalls) 36 and a fifth portion (e.g. hinge system) 26,
28, a sixth portion (lock, latch or sealing or attachment system, e.g., latch or snap enclosure) 16, 32, a seventh portion (port sealing area or port sealing stage area) 38, and an eighth portion (e.g. ramps and/or side rails for receiving and guiding the deployer). Case 1 is generally configured to house implantable device 200, but may be configured to house any device, instrument, component, apparatus, element, material, etc. for the purpose of ensuring and maintaining the integrity of such device, instrument, component, apparatus, element, material, etc.

Case 1 can be any number of "coupling systems", "mounting systems", "sealing systems"
or equivalents thereof, and represents any system for sealing, attaching, joining or connecting one portion to another, such as hinges 26, 28, snaps 16, 32, 12, 34 buttons, strings, hook, latch and loop fasteners, or other types of fasteners used to join the cover body 10 to the base body 30 to define a volume for receiving substances such as implantable devices and/or bioactive agents. FIGS. 2 and 3 show that the cover body 10 is coupled to the base body 30 for movement between a first or closed position (FIG. 3), in which the implantable device 200 contained therein is partially hidden, and a second or open position (FIG. 2), in which the implantable device 200 contained therein is revealed or exposed. As shown, cover body 10 and base body 30 may be joined by one or more, for example two, coupling systems that secure cover body 10 and base body 30 together in a manner that allows them to move independently of each other. One such coupling system is shown in FIG. 1 and includes, for example, a hinge mechanism 26,
28, pivotally coupling the cover body 10 to the base body 30 relative to each other. Hinge mechanisms 26 , 28 generally include a pivot shaft or rod 28 inserted into aperture or bore 26 . As shown, rod 28 is attached to the distal end of cover body 10 , but may be attached to base body 30 . The pivot rod 28 is attached to the cover body 1
It may be integrally formed with 0 or base body 30, or provided as a separate component. Another way of attaching the cover body 10 and the base body 30 together is the latch system 16, 32, 12, 34 as shown in FIG. Such a system may be provided to lock cover body 10 and base body 30 at proximal-most ends 16,32 or sidewalls 12,34. One purpose of the latching system illustrated herein is to prevent the implantable device 200 from sliding out or moving or moving out of the case 1 while it is contained therein. As illustrated, the user
Prior to loading or withdrawing the implantable device 200 within the case 1, the latch system 16, 32 is latched using the snap 14 to apply a deliberate force to the friction fit of the snap.
, 12, 34 are opened or uncoupled. One sidewall latch system 12,34
is shown, other similar latching systems may be incorporated entirely across the longitudinal axis of the case, depending in part on the shape and design of the implantable device, instrument, component, apparatus, element, material and the like contained therein.

In another aspect, the case comprises at least one alignment hole 22 generally located in the cover body 10 and a pin 24 complementary to the hole 22 in the base body 30, the pin 24 being inserted into the alignment hole 22 as shown in FIG. The case also provides functionality for interacting with or coupling with an embedding tool, for example a deployer, which is an embodiment of the present invention as described in more detail below. Another coupling system may be any number of foot projections (f
eet projection) 18. For example, FIG. 1 shows one embodiment in which the foot projection 18 is fitted, coupled or slotted within one section of the finger grip 36. As shown in FIG. Such foot projections are useful at least to inhibit movement or movement of the cover body 10 relative to the base body, preventing collapse of the cover body onto the base body thereby retaining and securing the implantable device 200 therein.

FIGS. 1-4 show a cover body 10 comprising at least one opening or window 20.
and base body 30 are shown. Window 20 is configured to allow one or more bioactive agents to enter and exit implantable device 200 . Illustratively, the window is
Although of rectangular or semi-circular shape, the window 20 is in part defined by the device,
It may be of any shape, design or number depending on the shape and design of the instruments, components, devices, elements, materials and the like contained therein. Although FIGS. 1-4 show windows 20 in symmetrical configurations in cover body 10 and base body 30, they need not be symmetrical so long as one or more bioactive agents can enter and exit the implantable device. Alternatively, FIG. 5 shows a window 20 structure in which the cover body 10 contains one large rectangular window 20 while the base body 30 contains two or more window 20 types. Depending still on the type and manner of device, instrument, component, apparatus, element, material and the like encased therein, the window may further comprise a mesh or thin polymer, film or matrix, some of which may allow visualization of the implantable device and provide similar permeability and passage to the nutrient medium.

The implantable device 200 exemplified herein is a macro-encapsulated implantable device that further includes a semipermeable polymeric material that is welded to and at least one implantable device port 202 that is used to fill or load the implantable device 200 with a therapeutic agent. However, modifications that do not depart from the device case embodiments described herein can be used to hold various implantable devices. Indeed, Applicants also describe a variety of contemplated two-dimensional and non-two-dimensional (e.g., three-dimensional) implantable devices including (but not limited to) self-expanding implantable devices, large-volume or macro-encapsulating implantable devices, two-dimensional and non-two-dimensional implantable devices, or three-dimensional macro-encapsulating implantable devices. Other encapsulated implantable devices are disclosed by the applicant, e.g., PCT/
US2014/022109, 3-DIMENSIONAL LARGE CAPACI
TY CELL ENCAPSULATION DEVICE and December 2011
U.S. Design Application No. 29/408,366 filed May 12, U.S. Design Application No. 29/408,368 filed December 12, 2011, U.S. Design Application No. 2 filed May 31, 2012
9/423,365, U.S. Design Application No. 29/447,94 filed March 13, 2013
4, U.S. Design Application No. 29/484,363 filed March 7, 2014, U.S. Design Application No. 29/484,359, U.S. Design Application No. 29/484,360, U.S. Design Application No. 2
9/484,357, 29/484,356, U.S. Design Application No. 29/484,355, U.S. Design Application No. 29/484,362 and U.S. Design Application No. 29/484,35,
Title 3-DIMENSIONAL LARGE CAPACITY CELL ENCA
PSULATION DEVICE.

1-3 show case 1 with port sealing stage area 38. FIG. Port sealing stage area 38 includes cutouts or openings in cover body 10 and base body 30 to receive at least a welding instrument or any sealing instrument capable of welding and/or sealing implantable device port 202 after implantable device 200 has been filled. Welding or sealing instruments may be handheld or stationary. Alternatively, the case 1 can also have port guides 40 that align the ports 202 within the port sealing stage area 38 .

To maintain the integrity of implantable device 200, case 1 is generally
4, may further include sidewalls having rigid or non-rigid grips, for example finger grips 36, which may facilitate handling and manipulation of the case 1. As shown in FIGS. This is beneficial, for example, during the cell loading process of the device and/or retrieval and transfer of the device, or manipulation by the operator. 1-4 show five finger grips 36 on each side wall of the case 1. FIG. However, FIG. 5 shows waisted finger grips 120, 122 and textured finger grips 124, 126, 1
28, engraved or etched finger grips 124, and rubberized or textured sticky finger grips 124, 128, showing other non-limiting and non-exclusive finger grip structures. Techniques and methods for making finger grips are well known in the art. Alternatively, handling, assembly,
If filling, sealing of implantable device ports, transfer, storage and transportation, and placement of implantable devices are to be automated, the finger grips may be optimized for such automation, or if so, may be unincorporated or incorporated elsewhere.

In one embodiment, implantable device 200 can undergo various quality control tests while in case 1 . Different test parameters are used depending on the quality control test. For example, dry or wet visual inspection with the naked eye and/or with a microscope can determine the quality of the implantable device. In one embodiment, first a dry visual inspection of the implantable device 200 may be performed outside the device case 1, and then
It is carried out inside case 1 using a microscope. In one embodiment, a wet visual inspection can also be performed by submerging the implantable device in a Petri dish filled with isopropyl alcohol (IPA), and the implantable device 200 is approximately 30, 40, 60, 80
or inflated for 100 seconds, during which visual inspection of both sides of the implantable device is performed. For both dry and wet visual inspection, a quality value index that can result in device defects (e.g., tears, punctures, leaks, or cosmetic anomalies that can lead to potential defects, etc.) can be determined with the naked eye and/or with a microscope.

In one embodiment, a compression damping quality control test may be performed on implantable device 200 within Case 1 . Compression decay is a non-destructive test performed on all implantable devices. In one embodiment, a pressure decay test may be performed prior to dry and wet visual inspection of the implantable device. Pressure decay tests include (but are not limited to) Raptor, Sprint
A variety of instruments can be used, including USON leak testers such as the iQ, Qualitek mR, Optima vT, and Vector, and preferably the USON Sprint iQ. For the compression decay test, the device case 1 containing the implantable device 200 is again completely submerged in the wetting solution containing IPA. The device
Preferably, it should remain stationary or motionless during this test, as any movement could potentially affect the measurements. Pressure decay is a measure of decay over time. A quality index measurement or value for an implantable device 200 that can pass the compression decay test is about 0.006 to about 0.020 psi, preferably about 10, 20, 30, 40, 50, 60 psi for about 10, 20, 30, 40, 50, 60, 80, or 100 seconds or more.
, 80, or 100 seconds or more, from about 0.008 to about 0.010 psi, preferably
about 0.01 for about 10, 20, 30, 40, 50, 60, 80, or 100 seconds or longer
0 psi.

In one embodiment, implantable devices 200 are quality tested in their respective cases 1 to protect the integrity of the device during quality control testing and reduce the number of manipulations or touches of the implantable device. This is because the implantable device remains within the case 1 during quality control testing, sterilization, filling into a device filling pouch assembly as described in more detail below, and filling of the implantable device 200 with therapeutic agents such as pancreatic progenitor cells, PDX1-positive pancreatic endoderm cells, endocrine cells, immature beta cells and the like.

Embodiments described herein describe tools and instruments for use with, or in conjunction with, implantable devices having therapeutic agents therein. Applicants have developed cell therapy for diabetes, in particular encapsulated cell therapy for the treatment of diabetes.
therapy) and have various endoderm- or definitive endoderm-lineage cells, particularly pancreatic-lineage cells, described in detail that are suitable for use with the embodiments described herein. See, for example, Applicants' at least US patent application Ser.
2/099,759 entitled METHODS OF PRODUCING PANCRE
ATIC HORMONES, U.S. patent application Ser. No. 12/61, filed Nov. 13, 2009
No. 8,659, entitled ENCAPSULATION OF PANCREATIC LIN
EAGE CELLS DERIVED FROM HUMAN PLURI POTEN
T STEM CELLS, U.S. Patent Application Serial No. 14/106, filed Dec. 12, 2013
, No. 330, entitled IN VITRO DIFFERENTIATION OF PLUR
IPOTENT STEM CELLS TO PANCREATIC ENDODER
M CELLS (PEC) AND IMMATURE BETA CELLS, 201
U.S. patent application Ser. No. 14/201,630, filed Mar. 7, 2014;
PCT/US2014/026529, IN VITRO DIFFEREN filed on 3rd
TIATION OF PLURIPOTENT STEM CELLS TO PAN
CREATIC ENDODERM CELLS (PEC) AND ENDOCRINE
CELLS provides details on mesendoderm and definitive endoderm lineage types of cells. In a preferred embodiment, the implantable device comprises a therapeutic agent, a living cell, an endoderm lineage cell, a definitive endoderm lineage cell, a progenitor cell, a progenitor cell differentiated from a stem cell (or human embryonic stem cells, fetal stem cells, umbilical cord blood stem cells, induced pluripotent stem cells, reprogrammed cells, parthenogenetic germ cells, germinal germ cells, and mesenchymal or hematopoietic stem cells, pancreatic progenitor cells, including those derived from methods now known or to be discovered in the future). , PDX1
Including positive pancreatic progenitor cells, endocrine progenitor cells, endocrine cells, immature beta cells, immature islet cells.

(Device Filling Pouch Assembly (DFPA))
FIG. 6 illustrates a non-limiting and non-exclusive embodiment of a Device Filling Pouch Assembly (DFPA) 50. As shown in FIG. Device Filling Pouch Assembly (DFPA) 50 serves not only as a sterilization bag for sterilization of Case 1 and implantable device 200 therein, but also as an assembly that facilitates filling of implantable devices, e.g., cell filling of implantable devices.

As shown in FIG. 6, DFPA 50 is an assembly or system of double peel pouches formed by releasably adhering first sheet 52 and second sheet 54 . The first sheet 52 has a transparent peelable transparent window 58 that allows the implantable device 200 and the case 1 to be seen, an entrance system and an exit system. The transparent window 58 includes a frangible (pull apart) seal along perimeters 56,60. The inlet system can include spacer tubes 62 . Spacer tube 62 may be permanently attached and mated to any fluid fitting, including (but not limited to) microbore Luers 66, 68, or may be removably attached to any fluid fitting. In one embodiment, the spacer tube 62 can receive an implantable device port 202 such that the port 202 is inserted into the spacer tube 62 and coupled therethrough to a cell reservoir, e.g., cells in the cell reservoir to fill the implantable device. The outlet system includes a drain port 72 and a drain port cap 74 for draining, depleting or emptying excess media, eg, excess nutrient media. The outermost portions of the inlet and outlet systems may further include a cap 74, for example a cleanable cap, with one or both systems covered by a shroud or sheath 70. Further, it will be appreciated that these entry and exit systems may be modified or optimized for the purpose of the cells or therapeutic agents intended to be loaded into the implantable device. In one embodiment, a suspension of cell aggregates is loaded into an implantable device, where several microbore features help minimize, reduce, and prevent clogging or crowding during the cell loading process. The DFPA alone or preferably together with the case 1 and the implantable device 200 therein is entirely sterilizable or made of sterilizable material or paper. In this example, the case 1 and implantable device 200 are sterilized at the same time, thus no further assembly of the case and implantable device after sterilization is required.

DFPA 50 also serves as an assembly or system, specifically a container or reservoir, for loading implantable device 200 with living cells or other therapeutic agents. In an example of cell therapy for the treatment of diabetes, the implantable device 200 contains pancreatic progenitor cells, such as PDX1-positive pancreatic endoderm cells, PECs, endocrine progenitor cells, endocrine cells,
or filled with immature β-cells. Methods for filling implantable devices include Baxter
International Inc. There is US Pat. No. 5,964,261 to (the "'261 Baxter patent"), which describes manual wetting, sterilization, filling and sealing via a syringe of an implanted device. However, the '261 Bax
In contrast to the implantable devices described in the ter patent, the implantable devices envisioned herein have a volumetric capacity that is at least six times greater than that of Baxter's implantable devices of much smaller volume, i.
250 μL versus 0 μL, and as such, the present invention contemplates a scaled wetting, sterilizing, filling and sealing manufacture and process for implantable devices of much larger volume. For example, these other implantable devices must be pre-wetted or primed by being immersed in or injected into a liquid mixture suitable for pre-wetting, such as sterile water, saline, or about 70%-100% ethanol, which is placed into the DFPA50 bag from the inlet system before the cells are loaded. In one embodiment herein, the interior of the implantable device may be primed or moistened with, for example, cell culture medium (not ethanol) just prior to loading the suspension of cell aggregates into the implantable device. The priming solution, in this example, can be the same solution (or medium) in which the cell aggregates are suspended. This is a '261 Baxte
At least one step less than previously disclosed methods, including the R patent, and residual ethanol is not a concern. The solution (cell culture medium, other nutrient medium, or other liquid mixture) is expelled out of the bag through an exit system that takes steps to remove any air from the implantable device. If water or ethanol is used to pre-wet the implantable device, then saline or cell culture media can be used to flush any remaining water or ethanol from the device. If cell loading requires pre-wetting of the implantable device, care should be taken to ensure that no air bubbles are trapped within the fluid pathways (e.g., inlet and outlet systems) that could interfere with cell loading. The volume of cell suspension and amount of media drawn into the syringe will depend on the maximum volumetric capacity or size of the implantable device. Less dense cell concentrations can be used if desired. For example, a final volume of 30 μL with 1×10 ⁷ cells may be used for a 20 μL implantable device. The prewetting and filling method described in the '261 Baxter patent involves many parts, is intended for research, not for clinical use, and is therefore difficult to maintain the sterile and/or aseptic environment necessary for regulatory compliance for any cellular product. The DFPA 50 can have a dual function (sterilization and filling assembly), thus reducing the likelihood of compromising, breaking or contamination of the implantable device within the case. Moreover, the device of the '261 Baxter patent is significantly smaller in size and volumetric capacity than the devices of the embodiments herein, making cell loading by syringe viable but impractical for scale-up purposes.

Because sterilization may be conventionally performed with radiation (e.g., ionizing radiation, gamma irradiation, electron beam irradiation), dry or hot humidity (e.g., steam (moist heat)) exposure, chemical (e.g., ethylene oxide exposure, etc.), the DFPA 50 of the present invention employs materials that allow the passage of active ingredients (gases) and water vapor, but not microbes or liquid water. A sterilization system that can sterilize the DFPA 50, Case 1 and implantable device 200 simultaneously is preferred, but some materials of Case 1 or implantable device 200 may not be compatible with high temperatures or irradiation, so ethylene oxide exposure is a suitable sterilization approach. Additionally, the sterilization approach may influence the selection of sterile packaging materials. The packaging materials described herein are compatible with most sterilization methods contemplated above.

The DFPA 50, and specifically the sheets 52, 54 of the exemplary embodiment, are formed by releasably adhering a base material or sterile paper, preferably made from polyester, polyvinyl chloride, polyethylene, polypropylene, ethylene copolymers, ionomeric resins, or materials such as gas permeable polyethylene cloth or polypropylene nonwoven fabric, which are strong, lightweight, flexible, and can withstand water, chemicals, and abrasion. or,
A thermoplastic transparent resin film that exhibits a suitable degree of adhesive strength and functions as a sealing layer between the first sheet 52 and the second sheet 54 can be used without impairing the gas permeability of the sheets.
It may be laminated between sheets and both materials may be sealed and adhered to each other. In other embodiments, DFPA 50 consists essentially of the same characteristics detailed for shipping bag 110 in FIG. 11 below.

The transparent window 58 is preferably made of biaxially oriented polyethylene terephthalate (Mylar™) or a polyester film made of oriented polyethylene terephthalate (PET) and used for its high tensile strength, chemical stability, dimensional stability, transparency, reflectivity, and gas and odor barrier properties. However, other materials (e.g., polyethylene) having properties substantially similar to those described above for the base materials of the DFPA 50 or transparent window 58 contemplated by the present invention, including any transparent polymeric film that maintains a sterility barrier under normal handling are also acceptable.

(device case storage bag)
7-9 illustrate non-limiting and non-exclusive embodiments of containers or storage bags 80 useful for storing implantable device 200 filled with cells. FIG. 9 is a perspective view of a bag 80 made in accordance with the present invention. The storage bag 80 may be made in a conventional configuration, including a pair of plastic sheets sealed with perimeter 168 and side and top frangible seals 100, hanger-providing portions 104 for maintaining the storage bag 80 in an upright position as needed, and various alignment holes 84. Alternatively, as shown in FIGS. 7 and 8, storage bag 80 may further include access ports 86, 92 permanently (eg, UV bonded) or removably coupled to fluid fittings 88, 94, 96 and cap 98.
, 90.

According to the present invention, the storage bag 80 is made of (but is not limited to) polyethylene and ethylene-vinyl-acetate (EVA), polyolefins, polyolefin blends,
Polycarbonate, polysulfone, polystyrene, di-2-ethylhexyl phthalate (
Polyvinyl chloride (P
VC), or optionally some triesters of trimellitic acid such as tri-2-ethylhexyl trimellitate (TOTM or TEHTM), and preferably made of clear, flexible, sterilizable, strong plastics including polyethylene and EVA. The material of choice for storage bag 80 is co-extruded polyethylene and EVA, which offers advantages over standard PVC material. This is because it reduces or prevents the leaching of plastic into the lumen of the storage bag 80 in which the cells are enclosed, and also reduces the prevailing environmental mercury levels commonly used in conventional PVC manufacturing. These films and the PVC plasticizers mentioned above are described, for example, in W.W. Warne
U.S. Pat. No. 4,280,497 to D.R. et al. U.S. Pat. Nos. 4,2 to Smith
22,379. However, similar plasticized bags have been found to release detectable amounts of ester-type plasticizers in the plasma of blood when the blood is stored in the bag for several days. Therefore, one embodiment of the storage bag of the present invention preferably does not leach plasticizer into the interior of the storage bag that holds and stores the live cells enclosed within the implantable device 200 and case 1 . Additionally, cells encapsulated within implantable devices require gas and nutrient exchange, so any flexible plastic material should preferably be gas permeable or impermeable to meet the metabolic demands of the stored cells and help preserve cell viability, especially for long-term storage.

FIG. 8 illustrates an alternative component that minimizes contact or touching of the case 1 and/or the implantable device 200 by loading the device case 1 into a storage bag 80 that helps maintain a sterile environment. As shown, there is a first sleeve 134 that protects the upper or upper or proximal portion of the storage bag 80, for example during subsequent sealing, and a second sleeve or guide 136 that is insertable within the first sleeve 134 to slide the case 1 and filled implantable device 200 into the storage bag 80. After the case 1 and filled implantable device 200 are placed in the storage bag 80, the bag contains (but is not limited to) Dulbecco's
Modified Eagle Medium (DMEM), or Connaught Med
CMRL medium, StemPro hESC SFM (Life Technology
es), or filled with a cell storage medium comprising a basal medium such as any suitable storage medium,
Such medium thereby soaks, completely covers, and keeps the implantable device 200 inside moist. After the storage bag 80 is filled, the upper opening is then sealed, followed by the side frangible 100 sealing, thereby forming a complete seal of the device case, implantable device and storage medium therein. Storage of the filled implantable device 200 in such a manner is suitable for periods of up to 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 25 days and 30 days or more at storage temperatures suitable to maintain viability of living cells prior to implantation. are

In one embodiment, storage bag 80 is formed by creating perimeter seal 168 and frangible seal 100 and then cutting the bag so that the bottom and side sections of perimeter seal 168 remain so that frangible seal 100 remains intact, while the top and top sections of the perimeter seal do not remain (e.g., these sections are cut or discarded). Alternatively, perimeter seal 168 may, depending on use, for example:
If the use does not require the use of frangible seal 100 or it does not need to be torn off, it may be kept beside frangible seal 100 and left except for the top opening.

(transport bag)
Figures 10 and 11 show a non-limiting and non-exclusive shipping bag 110 according to the present invention. The shipping bag 110 is formed from a first sheet 114 and a second sheet 116,
They are arranged to face each other and have three sides 112 to form a pouch.
are sealed together along the remaining sides, leaving an opening 116 suitable for receiving an item, for example, a device case storage bag 80 . In the illustrated embodiment, seat 11
4, 116 are generally square or rectangular in shape and are sealed to each other along seal areas 112 adjacent opposite edges of the bag and further along angularly extending seal areas at one edge of the bag. After the shipping bag 110 is filled with its contents by a user, the shipping bag 110 may be aseptically sealed to close the opening while preserving the sterility of the contents therein. The sealing of the sheets 114, 116 to each other is
It can be done using conventional thermal or ultrasonic sealing instruments well known in the art. To maintain aseptic handling, the shipping bag 110 may further include one or more handles 118 attached to the exterior of the bag that are used to open and hold the bag open while the contents are being filled without touching the interior of the bag.

In one embodiment, the material of the shipping bag of FIG. 11 is of properties substantially similar to the DFPA 50 of FIG. Both consist of an inner layer of heat-sealable clear thermoplastic polymer film, a laminate formed between two sheets, generally made of sterilizable material or paper. Preferably, the sheet is a polyolefin material, suitable examples of which include polypropylene, polyethylene, ethylene copolymers such as EAA, EMA, EVA,
and ionomer resins such as Surlyn® from DuPont or Iotek™ from ExxonMobil. Lamina and sheet thicknesses may suitably be from about 0.5 mils to about 4.0 mils, more preferably from about 1.5 mils to about 3.0 mils, and most preferably about 2 mils. Alternatively, as shown in FIG. 6 for DFPA 50, sheets 114, 116 may be of a transparent material that can provide strength, puncture resistance, dimensional stability, and durability as a bag. Materials suitable as transparent materials include polyethylene terephthalate (PET), nylon, polypropylene, polyethylene and cellophane. Biaxially oriented films are particularly preferred, such as biaxially oriented PET and biaxially oriented nylon. The thickness of the sheet may be about 0.36-2.0 mils, more preferably about 0.48-1.0 mils, and most preferably about 0.48 mils (48 ga). In addition, the sheets 114, 116 may be transparent or opaque and have a moisture barrier, for example a molecularly oriented polychlorotrifluoroethylene (PCTFE) fluoropolymer film. PCTFE films are transparent, biochemically inert,
Chemical resistant and free of plasticizers and stabilizers. Preferably, the molecularly oriented PCTFE film is a uniaxially stretched film. PCTFE fluoropolymer films are available from Honeywell, Inc.; are sold under the trade name Aclar®.

Conventional lamination and sealing methods include (but are not limited to) using adhesive spray, roll coating, knife over roll coating, wire rod coating or gravure coating. Suitable adhesives include solvent-based, water-based, or solvent-free adhesives, including acrylic adhesives, epoxy-cured polyester urethanes, moisture-cured polyester urethanes, and isocyanate-terminated polyester urethanes. Alternatively, the inner (i.e. middle) thin film layer may be extrusion coated onto sheet 114,
It may be formed directly on 116 and may be laminated directly to sheets 114, 116 using known adhesives and techniques, such as those described above, provided there is a transparent outer layer. If desired, the inside surface of the transparent layer may be reverse printed prior to lamination to provide a printed layer with product labels, pictures or other information. Sheets 114, 116 may be surface printed before or after lamination.

(Sizer)
FIG. 12 illustrates a non-limiting, non-exclusive surgical sizer according to the present invention. Sizer 15
0 includes a distal or pocket-forming portion 156 and a proximal or handle portion 154 . In the illustrated example, the pocket-forming portion 156 is generally shaped, ie, generally shaped to size the cavity for the implantable device 200 to be implanted. Certain detailed aspects of the actual implantable device, such as its ports and surface details, need not be reproduced in the pocket-forming portion 156, and indeed the omission of such details can help simplify manufacturing, reduce the number of potentially tissue-damaging features if not properly fabricated, and serve to create a cavity that allows the implantable device 200 to conform to the intended implantation site, regardless of its overall geometry. For example, in one embodiment, the sizer has a slightly tapered shape with a sharper leading edge to help spread the tissue at the implantation site.
In one embodiment, the pocket-forming portion 156 can have a non-two-dimensional shape, for example, the fine shape and curvature of the pocket-forming portion 156 may be useful in certain surgical procedures, anatomical sites,
and may be directed or tailored to the access path. Additionally, the pocket-forming portion 156 may be slightly larger than the actual dimensions of the implantable device, such as being enlarged 105%, 110%, 115%, 120%, 125%, or 130% or more of the dimensions of the implantable device. As with implantable device 200, its replica, pocket-forming portion 156, may be shaped to follow the contours of the relevant anatomical implantation site, e.g., contour to the curvature of the back, arms, abdomen, flanks, legs, etc., so as not to damage vulnerable tissue.

A proximal or handle portion 154 is an elongated substantially two-dimensional handle portion with a graspable handle 154 . The handle 154 can be etched, carved, or textured, or can include notches (or grooves) that naturally fit the human thumb or index and middle fingers to provide the surgeon with a suitable gripping surface. The notch is a circular hole,
It can take the form of elongated slots, or other shapes (eg, hook-shaped) and can have textured grips for additional feedback. or,
The entire proximal or handle portion, including the elongated shaft and graspable handle 154, may be textured while the distal or pocket-forming portion 156 remains relatively smooth. In still other embodiments, pocket-forming portion 156 may be permanently or removably coupled to proximal or handle portion 154 .

Nevertheless, the sizer 150 can have non-two-dimensional geometries, such as
The fine shape and curvature of the proximal or handle portion may be useful in certain surgical procedures, anatomical sites,
and may be directed or tailored to the access path. For example, the handle portion can have different sections (including flat and bent sections) with different radii of bend. Therefore, depending on the particular application, the sizer 15 according to the invention
0 can include ergonomic handle portions that are variably bent to assist the surgeon in placing the implantable device in applicable anatomical regions, for example, in specific layers of the dermis or between muscle and dermis.

Additionally, the sizer 150 can have various markings to aid in use. For example, the pocket-sizing portion 156 can include markings that can correspond to the locations of fixation features or other related structural features of the implantable device, or
It can act like a ruler to measure the implantation site. For example, in one embodiment of implantable device 200, pocket sizing portion 156 includes a suture ring (20 in FIG. 13).
4) has markings indicating suture fixation placement. The proximal or handle portion may also have markings on the elongated shaft and/or handle that may help the surgeon understand when the pocket sizing portion should not be pushed farther backwards, for example.

Additionally, the sizer can be used as a marking tool, such as a felt marker, a cauterizing tool, or
Other similar marking tools can be included that identify a number of locations closest to the anatomical location where the implant is to be placed.

Alternatively, the distance markings on the distal and proximal portions can have associated holes or slots that allow distances to be marked on tissue using any one of the methods described above. In one embodiment, pocket sizing portion 156 includes:
Aperture markings can be included to allow the desired placement of the implantable device to be marked, or the perimeter of the implantable device to be marked, or the placement of any sutures to be marked, for example, with a pen or cautery tool. Optionally, additional depth markings at specific distances along the handle portion (e.g., in millimeters indicating the distance to the distal end of the pocket-forming portion) can provide a guide to the surgeon when the implantable device has reached its optimal or required depth. The markings are generally tactile and/or visual in nature and may be, for example, grooves or notches that can be felt by touch, or simply lines drawn on the handle portion. Of course, the types and locations of markings described herein are merely exemplary, and those skilled in the art could readily adapt the markings to surgical tools for various other uses.

In some embodiments, the sizing and marking functions are not incorporated into the same instrument, but are instead provided by two separate surgical instruments.

Materials of manufacture for such sizers and/or marking tools are described in detail below.

(deployer device)
FIG. 13 illustrates one non-limiting and non-exclusive embodiment of a deployment device (also referred to as a “deployer” or deployer device, deployer tool, deployment tool, delivery tool, delivery device, implantation tool or implantation device) of the present invention.
As used herein, deployer or its equivalents such as "apparatus", "assembly", "two-dimensional assembly" or "system" refer to a tool or instrument capable of retracting, holding, transporting, delivering and placing a device such as in an implantable device. Generally, deployer 130 includes at least proximal and distal ends or portions. The distal ends further serve as holder or deployer ends 142 , 146 , 144 and the proximal ends further serve as handle ends 138 . The overall length of the deployer is preferably longer than the length of the indwelling implantable device.

The distal end further includes at least two holder plates 142, 146, an intermediate movable deployer plate or element 144, and an elongated shaft 130 including a handle 138 at its proximal end. The holder plate includes a cover plate 142 (or cover),
and a base plate 146 (or base) (or first and second holders or first and second plates, respectively). Thus, the baseplate is attached to shaft 158 and removably attached to handle 138, for example a graspable handle. The base plate 146 can have sidewalls 174, rails or guides that help position and hold the implantable device in place and also prevent the implantable device from slipping. Similarly, the cover plate 142 is
There may be rails or guides 170 to assist in relative movement of the cover plate, deployer and base plate with respect to each other. When assembled, the cover plate 1
42 and base plate 146 together form a holder that holds implantable device 200 . The distal end further includes a deployer plate 144 that can move between a cover plate 142 and a base plate 146 of the holder. The cover plate 142 and deployer plate 144 are assembled and removably attached or coupled to the base plate 146 by a base shaft 130 consisting of a rod-shaped shaft 158 with a superior groove along the axis of the shaft 158 . The cover plate 142 is
It may be removably attached or coupled to base plate 146 by a seat, channel or groove along the inner wall of base plate 146 . deployer plate 14
4 is connected or attached to the deployer shaft 152 . The deployer shaft 152 has a smaller diameter than the base holder plate shaft 158 and is therefore insertable into a groove or notch in the base shaft 158 and thus can move axially along the base shaft 158 or, in particular, the base shaft 1 .
It can move along the top or upper portion of 58 .

Deployer plate 144 and cover plate 142 further include control elements 140, 148 on cover plate 142 and deployer shaft 152, respectively.
or including control elements 140, 148 attached thereto, respectively. A control element 148 (also referred to as a first control element, cover plate control element, or cover control element) of the cover plate 142 is attached distally to a deployer control element 140 (also referred to as a second control element, deployer plate control element, or deployer control element). Deployer Plate 144, Deployer Shaft 158, and Deployer Control Element 1
40 are collectively referred to as deployer mechanisms or deployer devices. The deployer plate may also be modified or optimized, for example towards the distal end, to accommodate various types of implantable devices. For example, FIG. 13B is an exploded view of a device having a deployer plate with a distal end 160 that resembles the shape of suture holes or ears 204 of an implantable device.

The interconnectivity of these parts is best shown in FIG. 13I. FIG. 13I shows how the deployer shaft 152 is placed in the groove of the base shaft 158 so that the control elements 140, 148 wrap around both and prevent the deployer shaft 152 from exiting the base shaft groove. Cover plate 142 and deployer plate 144 , specifically cover control element 148 and deployer control element 140 , can threadably move within base plate 146 rod 158 or can move ratchetingly therein.

Control elements allow independent axial movement of cover plate 142 and deployer plate 144 relative to base plate 146 . control element 140, 1
48 also includes locking tabs, thumb operable wheels, rounded detents (e.g.
switch by twist or snap or actuator, additional force or provided by additional parts and the like that are available and known to those skilled in the art. For example, as shown in FIGS. 13C-13E, the user can unlatch (snap open) the device case 1 latch system and push the coverplate control element 148 proximally (i.e., behind) (eg, with thumb control) to force the baseplate 1 into position.
46 is inserted under implantable device 200 to cover and hold implantable device 200 . Since the coverplate control element 148 is attached distally to the deployer plate control element 140, when the coverplate control element 148 is moved back towards the handle or grippable handle 138, the deployer plate 1 is again similarly positioned.
44 also returns. However, to fully cover implantable device 200, cover plate 142 may be moved distally (forward) over implantable device 200 while deployer plate 144 and deployer shaft 152 are held stationary or in place. For example, referring to FIG. 13D, two control elements 140;
148 are alongside or directly adjacent to each other, whereas in FIG. 13E they are
Not side by side, spaced apart, preferably cover plate 142 and base plate 14
6 and are separated by approximately the same distance as the length of implantable device 200 .

Deployer 130 as exemplified herein uses implantable device 20 as described.
0, other two-dimensional and non-two-dimensional (e.g., three-dimensional) implantable devices, including semi-permeable two-dimensional and non-two-dimensional implantable devices, are also contemplated, including (but not limited to) self-expanding implantable devices, high volume two-dimensional and non-two-dimensional or three-dimensional macro-encapsulating implantable devices. Other encapsulated implantable devices are described by Applicant, e.g., PCT/US2 filed Mar. 7, 2014.
014/022109, 3-DIMENSIONAL LARGE CAPACITY
CELL ENCAPSULATION DEVICE and December 12, 2011
U.S. Design Application No. 29/408,366 filed on Dec. 12, 2011; U.S. Design Application No. 29/408,368 filed Dec. 12, 2011;
23,365; U.S. Design Application No. 29/447,944 filed March 13, 2013;
U.S. Design Application No. 29/484,363, filed March 7, 2014, U.S. Design Application No. 29
/484,359, U.S. Design Application No. 29/484,360, U.S. Design Application No. 29/4
84,357, U.S. Design Application No. 29/484,356, U.S. Design Application No. 29/484
, 355, U.S. Design Application No. 29/484,362 and U.S. Design Application No. 29/484.
, No. 35, title 3-DIMENSIONAL LARGE CAPACITY CELL
ENCAPSULATION DEVICE.

13F-13H illustrate implantable device 20 with sizer 156 as described above.
0 illustrates how an implantable device 200 (also referred to as a deployable implantable device) is deployed after the implantation site of 0 is ready for implantation. To deploy implantable device 200, the user pushes deployer control element 140 distally (i.e., forward) with one hand while simultaneously moving entire deployer 130 proximally (i.e., rearward) with the other hand. Implantable device 200 is thereby left in the prepared implantation site. The implantation site opening 150 can then be closed. Alternatively, hold deployer plate 144 in place and pull cover plate 142 and base plate 146, i.e., implantable device 2
00 and move away from the implantable site.

Although not shown, in one embodiment, deployer device 130 may further include a grasping system at or near the distal or holder end, or as part of or attached to deployer plate 144 . Such a grasping system is removably attachable to the implantable device 200 such that when the deployer plate 144 is retracted (moved proximally or rearward), the implantable device 200 moves accordingly onto the baseplate 146. However, the grasping system may be controlled from the proximal end of deployer 130, e.g., with additional control elements or actuators similar to those shown for the other two control elements 140, 148, or deployer control element 140 alone. In this example, such a grasping system may grasp the implantable device suture hole or ring 204 using, for example, some type of hook.

Similar to the sizer 156, the distal, holder or deployer ends 142, 146, 144 can have non-two-dimensional geometries, for example, the precise shape and curvature of the distal, holder or deployer ends 142, 146, 144 may be targeted or tailored to specific surgical procedures, anatomical sites, and access routes. As with sizer 156, deployer handle 138 can have a non-two-dimensional geometry, for example, the precise shape and curvature of the handle portion can be tailored to specific surgical procedures, anatomy, and access pathways. The handle portion can have various sections of curvature with different radii (including flat and curved sections). Thus, depending on the particular application, the deployer 130 according to the present invention can include ergonomic handle portions that are flexed differently to assist the surgeon in placing the implantable device in applicable anatomical regions, such as specific layers of the dermis, between the muscle and the dermis, or other superficial tissue layers. In one embodiment, rod or shaft 158 and handle 138 may have depth markings or associated marking tools.

In the illustrated embodiment, the distal or holder end, like the sizer, roughly shapes the implantable device 200 to be implanted. Some finer aspects of the actual implantable device, such as its ports and surface details, need not be reproduced in the pocket-forming portion 156, and in fact, omitting such details can help simplify manufacturing and serve to reduce the number of potentially tissue-damaging features if not properly fabricated. Nonetheless, some functional features of implantable device 200 may be incorporated into the deployer for better retrieval, retention, transport and deployment of the implantable device, for example the distal most end of deployer plate 144 may generally conform to the shape of the proximal end of implantable device 200. In this example, Figure 1
As shown in 3B, deployer plate 144 has two waists adapted to fit suture alignment holes or rings 204 at the proximal end of implantable device 200 . Other modifications can be made to accommodate other types of implantable devices. Additionally, the distal or holder ends 142, 146 may be slightly larger than the actual dimensions of the implantable device, e.g., 105%, 110%, 115%, 120%, 12
It may be magnified to 5%, or 130% or more. Similar to sizer 156, holder portion 142;
146, 144 are designed to avoid damaging sensitive tissue, e.g.
It can be shaped to follow the contours of the relevant anatomical implantation site, such as contouring to the curvature of the arms, abdomen, flanks, legs, and the like.

Figures 14A-14C illustrate another deployer embodiment of the present invention. The deployer generally includes an interconnected cover plate 142 and base plate 146 and lacks an intermediate deployer plate, operable control elements, or shaft handle as in the embodiments described above. Instead, the cover plate 142 covers the implantable device 20
An opening or window 162 for viewing 0 can be included. In one embodiment, the mounting system between the cover plate 142 and the base plate 146 includes the cover plate 142
It is removably attached by a notch on the base plate 146 that is inserted into the groove 166 of the base plate 146 . Movement of the two plates 142, 146 relative to each other may be accomplished by a texturing or gripping system 164 on the cover plate 142, for example shallow ridges 164 as shown in FIG. Control Element 1 of Deployer 130
40, 148 (e.g., thumb operable switches or wheels, locking tabs or rounded detent snaps) and finger grips 36 of the device case 1 (waisted grips 120, 122, textured grips 124, 126, 128, engraved or etched grips 124, and rubberized or textured sticky grips 124, 128). Still other embodiments similar to those may be used or applied to the cover plate 142 herein. Delivery and placement of implantable device 200 in one such embodiment does not depend on the deployer, rather the coverplate is moved forward, for example by being pushed forward (ie, distal) over ridge 164 .

In one embodiment of the invention, deployer 130 may include any number of holder systems at the distal end. This is because the holder plate is modified or adapted to the shape and design of the implantable device while still retaining the same conceptual slidable system for transporting and placing the implantable device.

In one embodiment of the present invention, the deployer 130 can be removably attached or coupled to commercially available or existing implantable or non-implantable devices, in which case only a nominal modification of the deployer as described herein is required.

In one embodiment of the invention, the control element may have other configurations and need not be a thumb or finger activated element as illustrated, but may be, for example, a thumb operable wheel or switch.

In one embodiment of the invention, the control element can be locked at a variety of different positions along the length or axis of the deployer, and such locking positions can depend on the implantable device.

(Manufacture of device cases, sizers and/or deployers)
Device cases, surgical sizers, marking tools and deployers as described herein can be made using injection molding, machining, stereolithography, or other 3D manufacturing (e.g., 3D printing) methods known to those skilled in the art. The fabrication of these instruments
It may be adapted to its intended application and use. For example, sizers, markers, or indwelling tools intended for repeated use may be made of an autoclave compatible material (i.e., a material that withstands the high pressure and temperature steam used within an autoclave to sterilize the tool), such as metals (e.g., stainless steel, gold, platinum, titanium, niobium, nickel,
nickel-titanium, cobalt-chromium alloys, molybdenum or molybdenum alloys, or alloys such as nitinol (titanium-nickel alloys), or alumina ceramics of similar properties), or some biocompatible polymeric materials such as polycarbonate, acrylonitrile butadiene styrene (ABS), high density polyethylene (HDPE), polystyrene, polyetheretherketone (PEEK), polypropylene, urethane, Teflon, polyethylene, polymethyl methacrylate, some epoxies, silicone or parylene, and other polyesters such as those mentioned above). Instruments intended for single use, on the other hand, may be manufactured from disposable polymeric materials, preferably those that degrade during autoclaving (e.g., caprolactone, lactic acid, glycolic acid, acrylic, polycarbonate or acrylonitrile butadiene styrene) to ensure that the instrument is not used more than once.

The exterior surfaces of device cases, surgical sizers, marking tools and deployers are preferably finished with non-stick and/or smooth edges to avoid damaging surrounding tissue that they contact during implantation. In some embodiments, the device is surface coated with Parylene® or similar hydrophobic material for optimization of smooth surfaces. Surface coatings can be applied to both metal tools and disposable plastic tools. For example, the device may be made of polymer (eg, polycarbonate, ABS, HDP)
E, polystyrene or polypropylene) is injection molded and then parylene
can be coated with C. Additionally, the underside of the appliance can be dipped in silicone or other materials commonly used by those skilled in the art to further optimize the surface. During the coating procedure, grooves, holes or constrictions in a portion of the shaft, handle or marking portion can be used to retain the instrument, thus minimizing the surface area uncoated by conventional coating procedures.

Various aspects of the invention are described herein. However, still others which are not specifically described but are mentioned are the applicant's U.S. patent application Ser.
6,408, entitled METHODS FOR CULTURE OF HESC ON;
FEEDER CELLS, U.S. Patent Application Serial No. 11/021, filed Dec. 23, 2004
, 618, entitled DEFINITIVE ENDODERM, U.S. patent application Ser.
DODERM, U.S. patent application Ser. No. 11/165,305, filed Jun. 23, 2005, entitled METHODS FOR IDENTIFYING FACTORS FOR DIF;
FERENTIATING DEFINITIVE ENDODERM, U.S. Patent Application Serial No. 11/573,662, filed Aug. 15, 2005, entitled METHODS FOR I;
NCREASING DEFINITIVE ENDODERM DIFFERENTI
ATION OF PLURIPOTENT HUMAN EMBRYONIC STE
M CELLS WITH PI-3 KINASE INHIBITORS, 2005
U.S. patent application Ser.
ESSING DORSAL AND VENTRAL FOREGUT ENDODE
RM, U.S. Patent Application Serial No. 12/093,590, filed Nov. 14, 2005, entitled MA
RKERS OF DEFINITIVE ENDODERM, U.S. patent application Ser.
LL CULTURE COMPOSITIONS AND METHODS OF U
SE THEREOF, U.S. patent application Ser. No. 11/588,6 filed Oct. 27, 2006
No. 93, title PDX1-EXPRESSING DORSAL AND VENTRAL
FOREGUT ENDODERM, U.S. patent application Ser.
681,687 entitled ENDOCRINE PROGENITOR/PRECURSO
R CELLS, PANCREATIC HORMONE-EXPRESSING CE
LLS AND METHODS OF PRODUCTION, U.S. Patent Application Serial No. 11/807,223, filed May 24, 2007, entitled METHODS FOR CULT
URE AND PRODUCTION OF SINGLE CELL POPULA
TIONS OF HESC, U.S. Patent Application Serial No. 11/773, filed July 5, 2007,
No. 944, entitled METHODS OF PRODUCING PANCREATIC H.
ORMONES, U.S. Patent Application Serial No. 11/860,494, filed September 24, 2007;
Title METHODS FOR INCREASING DEFINITIVE ENDO
DERM PRODUCTION, U.S. Patent Application Serial No. 12/09, filed April 8, 2008
No. 9,759, entitled METHODS OF PRODUCING PANCREATIC
HORMONES, U.S. Patent Application Serial No. 12/107,020, filed April 21, 2008
No., Title METHODS FOR PURIFYING ENDODERM AND P
ANCREATIC ENDODERM CELLS DERIVED FORM HU
MAN EMBRYONIC STEM CELLS, U.S. patent application Ser.
CREATIC LINEAGE CELLS DERIVED FROM HUMAN
PLURIPOTENT STEM CELLS, U.S. patent application Ser. No. 12/765,714 filed Apr. 22, 2010 and U.S. patent application Ser.
761,078, both entitled CELL COMPOSITIONS FROM DED;
IFFERENTIATED REPROGRAMMED CELLS, U.S. Patent Application Serial No. 11/838,054, filed Aug. 13, 2007, entitled COMPOSITIONS
AND METHODS USEFUL FOR CULTURING DIFFERE
NTIABLE CELLS, U.S. Patent Application No. 12/264, filed November 4, 2008
, No. 760, entitled STEM CELL AGGREGATE SUSPENSION C
OMPOSITIONS AND METHODS OF DIFFERENTIATI
ON THEREOF, U.S. patent application Ser. No. 13/259,15, filed Apr. 27, 2010
No., title SMALL MOLECULES SUPPORTING PLURIPOTE
NT CELL GROWTH, PCT/US11/256 filed Feb. 21, 2011
28, Title LOADING SYSTEM FOR AN ENCAPSULATION
DEVICE, 13/992,931 filed Dec. 28, 2010, entitled AGENT
S AND METHODS FOR INHIBITING PLURIPOTENT
STEM CELLS, U.S. Design Application No. 29/408, filed Dec. 12, 2011,
366, U.S. Design Application Serial No. 29/408,368, filed Dec. 12, 2011, 20
U.S. Design Application No. 29/423,365 filed May 31, 2012; U.S. Design Application No. 29/447,944 filed March 13, 2013; U.S. Provisional Patent Application No. 61/774,443 filed March 7, 2013, entitled SEMIPERMEABLE MACRO IMPL
ANTABLE CELLULAR ENCAPSULATION DEVICES, 2
U.S. Provisional Patent Application No. 61/775,480, entitled CRYOPRE, filed Mar. 8, 013;
SERVICE, HIBERNATION AND ROOM TEMPERATURE
URE STORAGE OF ENCAPSULATED PANCREATIC E
NDODERM CELL AGGREGATES, U.S. Provisional Patent Application No. 14/106,330, filed December 13, 2013, entitled IN VITRO DIFFERENTIA
TION OF PLURI POTENT STEM CELLS TO PANCRE
ATIC ENDODERM CELLS (PEC) AND ENDOCRINE C
ELLS, PCT/US2014/022065 filed March 7, 2014, entitled CRY
OPRESERVATION, HIBERNATION AND ROOM TEMP
ERATURE STORAGE OF ENCAPSULATED PANCREAT
IC ENDODERM CELL, PCT/US2014/ filed March 7, 2014
022109, SEMIPER MEABLE MACRO IMPLANTABLE C
ELLULAR ENCAPSULATION DEVICES, 14/201,630 filed March 7, 2014 and PCT/US2014 filed March 13, 2014
/026529, IN VITRO DIFFERENTIATION OF PLUR
IPOTENT STEM CELLS TO PANCREATIC ENDODER
M CELLS (PEC) AND ENDOCRINE CELLS, the contents of which are hereby incorporated by reference in their entirety.

The terms and expressions used herein are used as terms and expressions of description and not for purposes of limitation, and the use of such terms and expressions is not intended to exclude any equivalents of the features illustrated and described or portions thereof. moreover,
Having described several embodiments of the invention, it will be apparent to one skilled in the art that other embodiments incorporating the concepts disclosed herein may be used without departing from the spirit and scope of the invention. In particular, embodiments of the invention need not include all of the features, nor need all of the advantages described herein. Rather, they can include any subset or combination of features and advantages. Accordingly, the described embodiments are to be considered in all respects only as illustrative and not restrictive.

embodiment

Embodiments disclosed herein include the following.

device case

Embodiment 1: A case for holding an implantable two-dimensional device, comprising:
A case comprising a cover body and a base body that are removably coupled, the cover body having a first latching portion, the base body having a second latching portion configured to secure the cover body to the base body when the case is in a closed position, the cover body and the base body including a volume having at least one opening that allows passage of the one or more bioactive agents when secured.

The case of embodiment 1, wherein the case further comprises an implantable device.

The case of embodiment 1, wherein the implantable device is a semipermeable macroencapsulation device.

The case of embodiment 1, wherein the implantable device further comprises a therapeutic agent therein.

The case of embodiment 1, wherein the therapeutic agent is a living cell.

2. The case of embodiment 1, wherein the viable cells are progenitor cells that are distinct from stem cells in vitro.

The case of embodiment 1, wherein the progenitor cell is an endodermal lineage cell.

The case of embodiment 1, wherein the progenitor cells are pancreatic progenitor cells.

The case of embodiment 1, wherein the progenitor cells are PDX1-positive pancreatic endoderm cells.

The case of embodiment 1, wherein the viable cells are endocrine cells.

The case of embodiment 1, wherein the viable cells are immature beta cells.

The case of embodiment 1, wherein the stem cells are selected from the group consisting of human embryonic stem cells, fetal stem cells, cord blood stem cells, induced pluripotent stem cells, reprogrammed cells, parthenogenetic germ cells, germ germ cells, and mesenchymal or hematopoietic stem cells.

2. The case of embodiment 1, wherein the cover body and base body are configured to have at least one or more openings through which the one or more bioactive agents can pass.

2. The case of embodiment 1, wherein the cover body and the base body each have two openings.

2. The case of embodiment 1, wherein the cover body and base body each have four openings.

2. The case of embodiment 1, wherein the cover body and base body each have six openings.

2. The case of embodiment 1, wherein the cover body and base body each have eight openings.

2. The case of embodiment 1, further comprising a finger grip.

The case of embodiment 1 including a sealing or mounting system.

2. The case of embodiment 1, wherein the attachment system is selected from the group consisting of hinges, latches and snaps.

Embodiment 1, sterilizable alone or together with the implantable device within the case
case.

The case of embodiment 1, further comprising an implantable device port sealing area.

3. The case of embodiment 1, comprising a biocompatible polymeric material or metal.

Metals include stainless steel, gold, platinum, titanium, niobium, nickel, nickel titanium,
The case of embodiment 1 selected from the group consisting of cobalt-chromium alloys, molybdenum or molybdenum alloys, or alloys such as, for example, nitinol or alumina ceramics.

Biocompatible polymeric materials include polycarbonate, acrylonitrile butadiene styrene (ABS), high density polyethylene (HDPE), polystyrene, polyetheretherketone (PEEK), polypropylene, urethane, Teflon, polyethylene,
The case of embodiment 1 selected from the group consisting of polymethylmethacrylate, epoxy, silicone or parylene.

3. The case of embodiment 1, wherein the biocompatible polymeric material or metal can withstand autoclaving.

The case of embodiment 1, which is polycarbonate.

The case of embodiment 1, further comprising a finger grip and a port sealing area.

Embodiment 2: A case comprising a cover body and a base body, wherein the cover body and the base body are configured to be secured together in a closed state and configured to define an enclosure in the closed state such that an implantable device may be disposed between the cover body and the base body, and each having at least one window to allow passage of one or more bioactive agents.

Embodiment 3: A method of quality control testing of an implantable device, comprising: conducting at least one quality control test on an implantable device disposed within a device case; measuring at least one test parameter using at least one quality index value; and determining quality of the implantable device from the at least one quality index value.

4. The method of embodiment 3, wherein the quality control tests are dry visual inspection, wet visual inspection and pressure decay test.

4. The method of embodiment 3, wherein the quality control test is a dry visual inspection.

4. The method of embodiment 3, wherein the quality control test is a wet visual inspection.

4. The method of embodiment 3, wherein the quality control test is a compression decay test.

The implantable device has a compression decay value of from about 0.008 to about 0 for at least 20 seconds or more.
. 4. The method of embodiment 3, suitable for use when 010 psi.

The implantable device has a pressure decay value of from about 0.008 to about 0 for at least 20 seconds or more.
. 4. The method of embodiment 3, suitable for use when 010 psi.

The implantable device has a pressure decay value of from about 0.008 to about 0 for at least 30 seconds or more.
. 4. The method of embodiment 3, suitable for use when 010 psi.

The implantable device has a pressure decay value of from about 0.008 to about 0 for at least 40 seconds or more.
. 4. The method of embodiment 3, suitable for use when 010 psi.

The implantable device has a compression decay value of from about 0.008 to about 0 for at least 50 seconds or more.
. 4. The method of embodiment 3, suitable for use when 010 psi.

The implantable device has a pressure decay value of from about 0.008 to about 0 for at least 60 seconds or more.
. 4. The method of embodiment 3, suitable for use when 010 psi.

The implantable device has a pressure decay value of from about 0.008 to about 0 for at least 80 seconds or longer.
. 4. The method of embodiment 3, suitable for use when 010 psi.

4. The method of embodiment 3, wherein the implantable device is suitable for use when the pressure decay value is from about 0.008 to about 0.010 psi for at least 100 seconds or more.

Device filling pouch assembly

Embodiment 4: An assembly comprising a pouch holding an implantable device comprising at least one port, the pouch comprising an inlet system and an outlet system, the inlet system extending inwardly into the pouch and removably coupled to the implantable device port, removably coupled to the cell reservoir, and the outlet system extending outside the pouch.
assembly.

5. The assembly of embodiment 4, wherein the pouch further comprises peelable first and second sheets.

5. The assembly of embodiment 4, wherein the peelable first sheet of the pouch further comprises a peelable transparent window.

5. The assembly of embodiment 4, made of sterilizable material.

5. The assembly of embodiment 4, wherein the sterilizable material comprises polyolefin.

5. The assembly of embodiment 4, wherein the polyolefin is selected from the group consisting of polypropylene, polyethylene, ethylene copolymers and ionomer resins.

5. The assembly of embodiment 4, wherein the pouch is made of sterilizable material.

5. The assembly of embodiment 4, wherein the pouch is sterilized by heat, chemical and/or radiation sterilization.

5. The assembly of embodiment 4, wherein the pouch is sterilized by steam sterilization.

5. The assembly of embodiment 4, wherein the pouch is sterilized with ethylene oxide.

5. The assembly of embodiment 4, wherein the pouch is sterilized by ionizing radiation sterilization.

Embodiment 5: A method of filling an implantable device with live cells within a pouch, wherein the pouch includes peelable first and second sheets, an inlet system, and an outlet system, the implantable device case includes a cover body, a base body, and a port sealing area, the implantable device between the cover body and the base body of the implantable device case includes at least one port, the port connected to the inlet system of the pouch and further connected to a cell reservoir, the cell reservoir. can deliver live cells to an implantable device, whereby the implantable device is filled with cells within a pouch.

6. The method of embodiment 5, wherein the pouch, implantable device case and implantable device are sterilizable.

6. The method of embodiment 5, conducted under aseptic conditions.

6. The method of embodiment 5, wherein the pouch contains a cell nutrient medium having one or more bioactive agents.

6. The method of embodiment 5, wherein the nutrient medium is any cell culture medium suitable for maintaining living cells.

6. The method of embodiment 5, wherein the viable cells are pancreatic progenitor cells.

6. The method of embodiment 5, wherein the viable cells are progenitor cells that are distinct from stem cells in vitro.

6. The method of embodiment 5, wherein the progenitor cell is an endodermal lineage cell.

6. The method of embodiment 5, wherein the progenitor cell is a pancreatic progenitor cell.

6. The method of embodiment 5, wherein the pancreatic progenitor cells are PDX1-positive pancreatic endoderm cells.

6. The method of embodiment 5, wherein the viable cells are endocrine cells.

6. The method of embodiment 5, wherein the viable cells are immature beta cells.

6. The method of embodiment 5, wherein the implantable device is a semipermeable macroencapsulation device capable of allowing passage of one or more bioactive agents.

6. The method of embodiment 5, wherein the outlet port means is opened to empty excess nutrient medium.

surgical sizer

Embodiment 6: A surgical sizer including a pocket-forming portion and a handle portion, wherein the pocket-forming portion includes a leading edge for forming an implantation site.

7. The surgical sizer of embodiment 6, wherein the implantation site is for an implantable device.

7. The surgical sizer of embodiment 6, wherein the pocket-forming portion is greater than 100% of the dimensions of the implantable device.

7. The surgical sizer of embodiment 6, wherein the pocket-forming portion is about 105% of the dimensions of the implantable device.

7. The surgical sizer of embodiment 6, wherein the pocket-forming portion is about 110% of the dimensions of the implantable device.

7. The surgical sizer of embodiment 6, wherein the pocket-forming portion is about 120% of the dimensions of the implantable device.

7. The surgical sizer of embodiment 6, wherein the pocket-forming portion is about 125% of the dimensions of the implantable device.

7. The surgical sizer of embodiment 6, wherein the pocket-forming portion is about 130% of the dimensions of the implantable device.

7. The surgical sizer of embodiment 6, made of biocompatible polymeric material or metal.

Metals include stainless steel, gold, platinum, titanium, niobium, nickel, nickel titanium,
7. The surgical sizer of embodiment 6 selected from the group consisting of cobalt-chromium alloys, molybdenum or molybdenum alloys, or alloys such as nitinol or alumina ceramics.

Polymer material is polycarbonate, acrylonitrile butadiene styrene (ABS)
, high density polyethylene (HDPE), polystyrene, polyetheretherketone (PE
EK), polypropylene, urethane, Teflon, polyethylene, polymethylmethacrylate, epoxy, silicone or parylene.

7. The instrument of embodiment 6, wherein the metal consists essentially of stainless steel, titanium, niobium, nickel titanium or alloys.

7. The surgical sizer of embodiment 6, wherein the metal consists essentially of stainless steel.

7. The surgical sizer of embodiment 6, wherein the biocompatible polymeric material or metal can withstand autoclaving.

7. The surgical sizer of embodiment 6, wherein the pocket-forming portion comprises a replica of the implantable device.

Embodiment 6, wherein the surface of the pocket-forming portion has a curvature that complements the anatomical contours within the body
surgical sizer.

7. The surgical sizer of embodiment 6, wherein the pocket portion is two-dimensional.

7. The surgical sizer of embodiment 6, wherein the pocket portion is non-two-dimensional.

7. The instrument of embodiment 6, wherein the handle portion is two-dimensional.

7. The surgical sizer of embodiment 6, wherein the handle portion is non-two-dimensional.

7. The surgical sizer of embodiment 6, wherein the handle portion includes depth markings.

7. The surgical sizer of embodiment 6, further comprising a marking tool configured to mark tissue.

7. The surgical sizer of embodiment 6, wherein the instrument is one piece.

7. The surgical sizer of embodiment 6, wherein the instrument includes a pocket formation and the handle portion is removably coupled.

deployer

Embodiment 7: An apparatus for holding and deploying an implantable device, comprising a proximal end and a distal end, the distal end comprising a holder including a coverplate and a baseplate for holding the device, and a moveable deployer plate for deployment of the implantable device from the distal end.

8. The apparatus of embodiment 7, wherein the coverplate and baseplate house the implantable device.

8. The apparatus of embodiment 7, wherein the baseplate further comprises a shaft and a handle, the shaft removably coupled to the coverplate and the deployer plate.

8. The apparatus of embodiment 7, wherein the cover plate and deployer plate include control elements capable of axially moving the cover plate and deployer plate along the shaft.

8. The apparatus of embodiment 7, wherein the shaft and handle include depth markings.

8. The apparatus of embodiment 7, wherein the implantable device is deployed by moving the deployer plate axially distally relative to the base plate and the cover plate, thereby deploying the implantable device.

8. The apparatus of embodiment 7, wherein the control element is a thumb operable wheel or switch.

8. The apparatus of embodiment 7, wherein the first and second control elements are actuators.

8. The apparatus of embodiment 7, wherein the implantable device is a two-dimensional device.

8. The apparatus of embodiment 7, wherein the implantable device is a self-expanding device.

8. The apparatus of embodiment 7, wherein the implantable device is a semipermeable macroencapsulation device.

8. The apparatus of embodiment 7, wherein the implantable device contains a therapeutic agent therein.

8. The device of embodiment 7, wherein the therapeutic agent is a living cell.

8. The apparatus of embodiment 7, wherein the viable cells are progenitor cells that are distinct from stem cells in vitro.

8. The apparatus of embodiment 7, wherein the stem cells are selected from the group consisting of human embryonic stem cells, fetal stem cells, cord blood stem cells, induced pluripotent stem cells, reprogrammed cells, parthenogenetic germ cells, germ germ cells, and mesenchymal or hematopoietic stem cells.

8. The apparatus of embodiment 7, wherein the progenitor cells are endoderm-lineage cells.

8. The apparatus of embodiment 7, wherein the progenitor cells are pancreatic progenitor cells.

8. The apparatus of embodiment 7, wherein the progenitor cells are PDX1-positive pancreatic endoderm cells.

8. The apparatus of embodiment 7, wherein the progenitor cells are endocrine cells.

8. The apparatus of embodiment 7, wherein the viable cells are immature beta cells.

Embodiment 8: An assembly for deploying an implantable device, comprising a first holder, a second holder comprising a rod or shaft and a handle, and a deployer mechanism between the first and second holders, the deployer mechanism adapted to effect deployment of the implantable device, the first holder and the deployer mechanism comprising:
removably coupled to the second holder rod and movable along the longitudinal axis of the rod;
An assembly wherein movement of the deployer mechanism relative to the first and second holders delivers or deploys the implantable device.

9. The assembly of embodiment 8, wherein the first holder includes a first control element for axially moving the first holder.

9. The assembly of embodiment 8, wherein the deployer includes a distal end and a proximal end, the distal end being between the first and second holders and the proximal end interconnected to the rod.

9. The assembly of embodiment 8, wherein the deployer mechanism further comprises a second control element for axially moving the deployer.

9. The assembly of embodiment 8, wherein the second control element of the deployer mechanism is threadably movable within the rod.

a second control element of the deployer mechanism is ratcheted within the rod;
Assembly of embodiment 8.

9. The assembly of embodiment 8, wherein the first and second control elements are thumb operable wheels or switches.

9. The assembly of embodiment 8, wherein the first and second control elements are actuators.

9. The assembly of embodiment 8, wherein the rod and handle of the first holder include depth markings.

9. The assembly of embodiment 8, wherein the implantable device is a two dimensional device.

9. The assembly of embodiment 8, wherein the implantable device is a self-expanding device.

9. The assembly of embodiment 8, wherein the implantable device is a semipermeable macroencapsulation device.

9. The assembly of embodiment 8, wherein the implantable device contains a therapeutic agent therein.

9. The assembly of embodiment 8, wherein the therapeutic agent is a living cell.

9. The assembly of embodiment 8, wherein the viable cells are progenitor cells that are distinct from stem cells in vitro.

9. The assembly of embodiment 8, wherein the progenitor cell is an endodermal lineage cell.

9. The assembly of embodiment 8, wherein the progenitor cells are pancreatic progenitor cells.

9. The assembly of embodiment 8, wherein the progenitor cells are PDX1-positive pancreatic endoderm cells.

9. The assembly of embodiment 8, wherein the living cells are endocrine cells.

9. The assembly of embodiment 8, wherein the viable cells are immature beta cells.

Metals include stainless steel, gold, platinum, titanium, niobium, nickel, nickel titanium,
9. The assembly of embodiment 8 selected from the group consisting of cobalt-chromium alloys, molybdenum or molybdenum alloys, or alloys such as nitinol or alumina ceramics.

Polymer material is polycarbonate, acrylonitrile butadiene styrene (ABS)
, high density polyethylene (HDPE), polystyrene, polyetheretherketone (PE
EK), polypropylene, urethane, Teflon, polyethylene, polymethylmethacrylate, epoxy, silicone or parylene.

9. The assembly of embodiment 8, wherein the metal consists essentially of stainless steel, titanium, niobium, nickel titanium or alloys.

9. The assembly of embodiment 8, wherein the metal consists essentially of stainless steel.

Embodiment 9: A method of deploying an implantable device for cell therapy, comprising positioning an assembly comprising the implantable device and a holder having first and second plates and a deployer plate at an anatomical implantation site, the second holder further comprising a rod and a handle, the deployer element being coupled to the rod and movable along an axis of the rod, and moving the deployer element relative to the rod and the first and second holders, thereby moving the implantable device to the anatomical implantation site. is placed or delivered.

10. The method of embodiment 9, wherein the implantable device is a two-dimensional device.

10. The method of embodiment 9, wherein the implantable device is a self-expanding device.

10. The method of embodiment 9, wherein the implantable device is a semipermeable macroencapsulation device.

10. The method of embodiment 9, wherein the implantable device contains a therapeutic agent therein.

10. The method of embodiment 9, wherein the therapeutic agent is a living cell.

10. The method of embodiment 9, wherein the viable cells are progenitor cells that are distinct from stem cells in vitro.

10. The method of embodiment 9, wherein the progenitor cell is an endodermal lineage cell.

10. The method of embodiment 9, wherein the progenitor cell is a pancreatic progenitor cell.

10. The method of embodiment 9, wherein the progenitor cells are PDX1-positive pancreatic endoderm cells.

10. The method of embodiment 9, wherein the viable cells are endocrine cells.

10. The method of embodiment 9, wherein the viable cells are immature beta cells.

To maintain the integrity of the implantable device 200, the case 1 may generally further include sidewalls having rigid or non-rigid grips, for example finger grips 36, which can make the case 1 easier to handle and manipulate, as shown in FIGS. This is beneficial, for example, during the cell loading process of the device and/or retrieval and transfer of the device, or manipulation by the operator. 1-4 show five finger grips 36 on each side wall of the case 1. FIG. However, FIG. 4 illustrates other non-limiting and non-exclusive finger grip structures, including waisted finger grips 120, 122, textured finger grips 124, 126, 128, engraved or etched finger grips 124, and rubberized or textured sticky finger grips 124, 128. Techniques and methods for making finger grips are well known in the art. Alternatively, if handling, assembly, filling, sealing of implantable device ports, transfer, storage and transportation, and implantable device placement are to be automated, the finger grips may be optimized for such automation, or if so, may be unincorporated or incorporated elsewhere.

Claims (56)

1. An apparatus for holding and deploying an implantable device, comprising a proximal end, a distal end, the distal end comprising a holder including a cover plate and a base plate for holding the device, and a movable deployer plate for deploying the implantable device from the distal end. 2. The apparatus of claim 1, wherein the coverplate and the baseplate accommodate the implantable device. 2. The base plate further comprises a shaft and a handle, the shaft removably coupled to the cover plate and the deployer plate.
The apparatus described in . 2. The apparatus of claim 1, wherein the cover plate and the deployer plate include control elements capable of axially moving the cover plate and the deployer plate along the shaft. 2. The device of claim 1, wherein the shaft and handle include depth markings. 2. The apparatus of claim 1, wherein the implantable device is deployed by moving the deployer plate axially distally relative to the base plate and the cover plate, thereby deploying the implantable device. 2. The device of claim 1, wherein the control element is a thumb-operable wheel or switch. 2. The device of claim 1, wherein the first control element and the second control element are actuators. 11. The apparatus of Claim 1, wherein the implantable device is a two-dimensional device. 3. The apparatus of Claim 1, wherein the implantable device is a self-expanding device. 3. The apparatus of claim 1, wherein the implantable device is a semipermeable macroencapsulation device. 3. The apparatus of claim 1, wherein the implantable device contains a therapeutic agent therein. 3. The device of claim 1, wherein said therapeutic agent is a living cell. 2. The device of claim 1, wherein said living cells are progenitor cells that are distinct from stem cells in vitro. 2. The apparatus of claim 1, wherein the stem cells are selected from the group consisting of human embryonic stem cells, fetal stem cells, cord blood stem cells, induced pluripotent stem cells, reprogrammed cells, parthenogenetic germ cells, germ germ cells, and mesenchymal or hematopoietic stem cells. 2. The device of claim 1, wherein the progenitor cells are endoderm cells. 2. The device of claim 1, wherein the progenitor cells are pancreatic progenitor cells. 2. The device of claim 1, wherein the progenitor cells are PDX1-positive pancreatic endoderm cells. 2. The device of claim 1, wherein said progenitor cells are endocrine cells. 2. The device of claim 1, wherein said living cells are immature beta cells. An assembly for deploying an implantable device, comprising:
a first holder;
a second holder comprising a rod or shaft and a handle;
a deployer mechanism between the first holder and the second holder;
the deployer mechanism is adapted to effect deployment of the implantable device;
said first holder and said deployer mechanism being removably coupled to a rod of said second holder and movable along a longitudinal axis of said rod;
Movement of the deployer mechanism relative to the first and second holders causes
the implantable device is delivered or deployed;
assembly. 22. The assembly of claim 21, wherein said first holder includes a first control element for axially moving said first holder. 3. The deployer includes a distal end and a proximal end, the distal end being between the first and second holders, the proximal end being interconnected to the rod.
1. The assembly of claim 1. 22. The assembly of claim 21, wherein the deployer mechanism further includes a second control element for axially moving the deployer. 22. The assembly of claim 21, wherein the second control element of the deployer mechanism is threadably movable within the rod. 22. The assembly of claim 21, wherein the second control element of the deployer mechanism is ratchet-movable within the rod. 22. The assembly of claim 21, wherein the first and second control elements are thumb operable wheels or switches. 22. The assembly of claim 21, wherein said first control element and second control element are actuators. 22. The assembly of claim 21, wherein said rod and said handle of said first holder include depth markings. 22. The assembly of claim 21, wherein said implantable device is a two-dimensional device. 22. The assembly of claim 21, wherein said implantable device is a self-expanding device. 22. The assembly of Claim 21, wherein the implantable device is a semipermeable macroencapsulation device. 22. The assembly of claim 21, wherein the implantable device contains a therapeutic agent therein. 22. The assembly of Claim 21, wherein said therapeutic agent is a living cell. 22. The assembly of claim 21, wherein said living cells are progenitor cells distinct from stem cells in vitro. 22. The assembly of claim 21, wherein said progenitor cell is an endodermal lineage cell. 22. The assembly of claim 21, wherein said progenitor cells are pancreatic progenitor cells. 22. The assembly of claim 21, wherein said progenitor cells are PDX1-positive pancreatic endoderm cells. 22. The assembly of claim 21, wherein said living cells are endocrine cells. 22. The assembly of claim 21, wherein said living cells are immature beta cells. Metals include stainless steel, gold, platinum, titanium, niobium, nickel, nickel titanium,
22. The assembly of claim 21 selected from the group consisting of cobalt-chromium alloys, molybdenum or molybdenum alloys, or alloys such as nitinol or alumina ceramics. Polymer material is polycarbonate, acrylonitrile butadiene styrene (ABS)
, high density polyethylene (HDPE), polystyrene, polyetheretherketone (PE
EK), polypropylene, urethane, Teflon, polyethylene, polymethylmethacrylate, epoxy, silicone, or parylene. 22. The assembly of claim 21, wherein said metal consists essentially of stainless steel, titanium, niobium, nickel titanium, or alloys. 22. The assembly of claim 21, wherein said metal consists essentially of stainless steel. A method of deploying an implantable device for cell therapy, comprising:
positioning an assembly comprising an implantable device and a holder having a first plate and a second plate and a deployer plate at an anatomical implantation site, the second holder further comprising a rod and a handle, a deployer element coupled to the rod and movable along an axis of the rod;
moving the deployer element relative to a rod and first and second holders, thereby placing or delivering the implantable device at the anatomical implantation site. 46. The method of claim 45, wherein said implantable device is a two-dimensional device. 46. The method of Claim 45, wherein the implantable device is a self-expanding device. 46. The method of claim 45, wherein the implantable device is a semipermeable macroencapsulation device. 46. The method of claim 45, wherein the implantable device contains a therapeutic agent therein. 46. The method of claim 45, wherein said therapeutic agent is a living cell. 46. The method of claim 45, wherein said living cells are progenitor cells that are distinct from stem cells in vitro. 46. The method of claim 45, wherein said progenitor cell is an endodermal lineage cell. 46. The method of claim 45, wherein said progenitor cells are pancreatic progenitor cells. 46. The method of claim 45, wherein said progenitor cells are PDX1-positive pancreatic endoderm cells. 46. The method of claim 45, wherein said living cells are endocrine cells. 46. The method of claim 45, wherein said living cells are immature beta cells.