WO2021016055A1 - Greffe composite à lumière creuse imprégnée de poly (sébacate de glycérol) - Google Patents

Greffe composite à lumière creuse imprégnée de poly (sébacate de glycérol) Download PDF

Info

Publication number
WO2021016055A1
WO2021016055A1 PCT/US2020/042454 US2020042454W WO2021016055A1 WO 2021016055 A1 WO2021016055 A1 WO 2021016055A1 US 2020042454 W US2020042454 W US 2020042454W WO 2021016055 A1 WO2021016055 A1 WO 2021016055A1
Authority
WO
WIPO (PCT)
Prior art keywords
pgs
lumen
fibers
vascular graft
biologically
Prior art date
Application number
PCT/US2020/042454
Other languages
English (en)
Inventor
Brian P. Ginn
Peter D. Gabriele
Original Assignee
The Secant Group, Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Secant Group, Llc filed Critical The Secant Group, Llc
Publication of WO2021016055A1 publication Critical patent/WO2021016055A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001—Designing or manufacturing processes

Definitions

  • the present disclosure is generally directed to grafts. More specifically, the present disclosure is directed to hollow lumen composite grafts infused with poly(glycerol sebacate) (PGS).
  • PPS poly(glycerol sebacate)
  • Conventional synthetic vascular grafts lack signaling cues to support regeneration of vascular tissue and have a poor capacity for biodegradation.
  • Biologically-derived materials such as, for example, fibrin or collagen, have the potential to match the cell signaling moieties present in the native extracellular matrix (ECM) but have poor mechanical properties that limit their use.
  • ECM extracellular matrix
  • biologically-derived materials are prone to cracking, which, in addition to leading to device failure, also leads to a large variation in the efficacy of grafts made from such materials.
  • a hollow lumen composite vascular graft infused with a PGS resin as disclosed herein, overcomes one or more of the above-mentioned shortcomings.
  • a process of forming a hollow lumen composite vascular graft includes infusing a plurality of fibers of at least one biologically-derived material with poly(glycerol sebacate) (PGS). The process also includes forming a lumen wall from the plurality of fibers and the PGS with the plurality of fibers being axially oriented in the lumen wall.
  • PGS poly(glycerol sebacate)
  • a hollow lumen composite vascular graft in another embodiment, includes a lumen wall having an annular cross section, an inner lumen surface, and an exterior lumen surface.
  • the lumen wall includes a plurality of fibers of at least one biologically-derived material and a matrix of PGS infusing the plurality of fibers.
  • the plurality of fibers are axially oriented in the lumen wall.
  • FIG. 1 schematically shows a cross sectional view of a PGS-infused hollow lumen composite vascular graft in an embodiment of the present disclosure.
  • FIG. 1A schematically shows a lengthwise view of the exterior lumen surface of the graft of FIG. 1.
  • FIG. IB schematically shows a lengthwise view of the outer graft surface of the graft of FIG. 1.
  • FIG. 2 schematically shows a longitudinal sectional view of a PGS-infused hollow lumen composite vascular graft formed on a mandrel in an embodiment of the present disclosure.
  • FIG. 3 schematically shows a process of forming a PGS-infused hollow lumen composite vascular graft on a mandrel in an embodiment of the present disclosure.
  • FIG. 4 schematically shows an extrusion process of forming a PGS-infused hollow lumen composite vascular graft with micropatteming in an embodiment of the present disclosure.
  • FIG. 5 schematically shows an extrusion process of forming a PGS-infused hollow lumen composite vascular graft with fiber fragments in an embodiment of the present disclosure.
  • a hollow lumen composite vascular graft includes walls composed of naturally-derived biomaterials infused with poly(glycerol sebacate) (PGS).
  • Naturally-derived materials such as fibrin or collagen, provide physiological signaling cues for cells that match those of the extracellular matrix (ECM) of the native vascular structure.
  • ECM extracellular matrix
  • PGS infusion improves the mechanical properties of the hollow lumen vascular graft and may be used to further tune the cell response based on details of the PGS and the infusion, such as, for example, the PGS formulation, the elastic properties, and/or the degradation timeline.
  • a composition of matter includes PGS with properties tuned to improve performance of a hollow lumen vascular graft.
  • an article of manufacture includes a hollow lumen vascular graft infused with PGS.
  • FIG. 1 shows a cross sectional view of a PGS-infused hollow lumen composite vascular graft 10 with a lumen wall 12 of axially-oriented fibers 14 embedded in a PGS matrix 16 and a textile overbraid 18 on the exterior lumen surface 20 of the lumen wall 12.
  • the fibers 14 are of at least one biologically-derived material.
  • FIG. 1A shows a longitudinal view of the exterior lumen surface 20 of the lumen wall 12 with the axially-oriented fibers 14 embedded in the PGS matrix 16.
  • FIG. 1 B shows a longitudinal view of the textile overbraid 18 at the outer graft surface 30 of the PGS-infused hollow lumen composite vascular graft 10.
  • the PGS-infused hollow lumen composite vascular graft 10 includes a lumen wall 12 having an exterior lumen surface 20 and an inner lumen surface 22 defining a cylindrical central hollow lumen 24.
  • the lumen wall 12 has an annular cross section and includes axially-oriented biological fibers 14 in a PGS matrix 16.
  • the PGS-infused hollow lumen composite vascular graft 10 also includes an overbraid 18 on the exterior lumen surface 20 of the lumen wall 12.
  • a process includes infusing a biologically-derived material with PGS in the formation of a PGS-infused hollow lumen vascular graft 10.
  • FIG. 2 shows a PGS-infused hollow lumen composite vascular graft 10 being formed on a mandrel 40 and in an outer mold 42.
  • the process of forming the PGS-infused hollow lumen composite vascular graft 10 includes bundling biological fibers 14 that are preferably texturized to enhance cellular outgrowth around the mandrel 40 and securing the fibers 14 on the ends via sutures or an adhesive.
  • the process then includes dip coating the bundle into a PGS solution to fill in the space between the fibers 14 with a PGS matrix 16 that may then be cured or crosslinked.
  • the total thickness of the graft may be controlled based on the extent of fiber bundling.
  • the mandrel 40 that is subsequently removed extends coaxially past the ends of the outer mold 42.
  • FIG. 3 shows a process of forming a PGS-infused hollow lumen composite vascular graft 10 in an annular space 50 between an inner mold 52 and an outer mold 54.
  • the process includes loading the annular space 50 between the inner mold 52 and the outer mold 54 with fibers 14.
  • the process of forming the PGS-infused hollow lumen composite vascular graft 10 also includes infusing the annular space 50 containing biological filaments or fibers 14 with a PGS matrix 16.
  • the process further includes removing the inner mold 52 and the outer mold 54.
  • An overbraid 18 may then be applied to the exterior lumen surface 20 of the lumen wall 12.
  • FIG. 4 shows a process of forming a vascular graft 10 that includes mixing PGS resin directly with fibers 14 of a biological component to form a mixture 60 of the fibers 14 in a PGS matrix 16 that is extruded through an extrusion nozzle 62 containing a micropattemed inner surface 64 and/or a micropattemed outer surface 66 on the extrusion nozzle 62 to induce grooving along the longitudinal direction of the exterior lumen surface 20 and/or the inner lumen surface 22, respectively, of the lumen wall 12.
  • the extrusion forms the lumen wall 12 of a PGS matrix 16 mixed with fibers 14 of the biological component to have a micropattemed exterior lumen surface 20 and/or inner lumen surface 22 based on the micropattemed shape of the extrusion nozzle 62.
  • the process of forming the vascular graft 10 further includes placing the tube of PGS-infused biological fibers onto a mandrel 40 and placing a low angle overbraid 18 over the exterior lumen surface 20 to further enhance the mechanical properties of the vascular graft 10 and provide contour guidance for smooth muscle cells.
  • a low braid angle is a braid angle of 130 degrees or less.
  • FIG. 5 shows a process of forming a vascular graft 10 that includes mixing PGS resin directly with fibers 14 of a biological component to form a mixture 60 of the fibers 14 in a PGS matrix 16 and extmding the mixture 60 through a narrow nozzle 70 that aligns the fibers 14 with the flow of the mixture 60 coming out of the nozzle 70 upon extmsion.
  • the nozzle 70 may have a circular or annular cross section producing a lumen wall 12 having the same shape.
  • the PGS may be any form of a polymer resulting from copolymerization of glycerol and sebacic acid.
  • the PGS may include different stoichiometric ratios of glycerol and sebacic acid, different molecular weights, different degrees of branching, and different polydispersity based on preferred properties of the lumen wall 12.
  • the PGS resin is formed by a water-mediated synthesis process, such as described in U.S. Patent No. 9,359,472 issued June 7, 2016.
  • the hollow lumen composite vascular graft 10 is infused with PGS in a variant form, such as, for example, poly(glycerol sebacate) urethane (PGSU) or a pH- buffering PGS, such as, for example, disclosed in U.S. Patent Application Publication No. 2019/0218506, published July 18, 2019, which is incorporated by reference in its entirety.
  • PGS poly(glycerol sebacate) urethane
  • the PGS is crosslinked with the biologically-derived material following the infusion.
  • a process includes combining fibers 14 of biologically-derived materials through infusion with PGS to reinforce and tune the material properties of the vascular graft.
  • Tuning may include, but is not limited to, selecting a ratio of the PGS to the biologically-derived material being reinforced, altering the PGS formulation to affect composite properties, such as, for example, including one or more amino acids with the PGS rather than using neat PGS, selecting a glycerohsebacic acid ratio within a range of such ratios between 1:0.25 and 1:2, selecting a degree of curing of the PGS to adjust the elasticity, leaving the PGS in an uncured or substantially uncured state such that the PGS provides a crack sealant function in the composite, selecting a molecular weight of the PGS to affect the retention time (when used as a resin), selecting a stoichiometric ratio of isocyanate-to-hydroxyl between 1:0.25 and 1 :2 to provide a level of PGSU crosslinking, or combinations thereof.
  • the composite vascular graft 10 has superior properties to other synthetic vascular grafts not including both the biologically-derived material and the PGS.
  • the infusion of elastomeric PGS into biologically-derived fibrous materials 14 improves the mechanical properties of the resulting composite by increasing the flexibility of a vascular graft 10 while maintaining the presence of native integrin-binding sites found in the biologic material.
  • the relative concentration of the PGS is higher than the biological phase, and the PGS matrix acts as the primary mechanical graft support structure with enhanced attachment via the biological phase domains.
  • the relative concentration of PGS is lower than the biological phase, and the PGS domains act to prevent crack propagation, as the elasticity of the PGS imparts a high toughness that absorbs crack energy.
  • the improved strength of a vascular graft 10 due to infusion of PGS into the biologically-derived material reduces the minimum lumen wall 12 thickness required to maintain a functional lumen. This simultaneously improves the flexibility of the grafit 10 and improves the ability of smooth muscle cells to‘feel’ pulsatile flow to guide their orientation and help them better communicate with endothelial cells in the lumen.
  • orientation is imparted to the luminal and exterior structure by materials processing, such as, for example, extrusion.
  • extruded tubes with longitudinal microchannels (to guide endothelial alignment) in the lumen walls 12 are prepared through a core-shell die having grooves on the shell die, as shown in FIG. 4.
  • an overbraid 18 with a low braid angle provides additional mechanical support while helping to guide the initial orientation of smooth muscle cells to be perpendicular to the direction of fluid flow in the lumen.
  • the biological fibers 14 there is some exposure of the biological fibers 14 at the inner lumen surface 22 to provide attachment sites for the cells.
  • the biological fibers 14 may be slightly below the PGS surface and exposed as the PGS erodes in the lumen.
  • a PGS formulation with poor cell attachment properties may be used initially to prevent blood clotting following vascular repair, but once the initial wound healing response is complete, the endothelial cells may invade from the native vascular tissue along the later-exposed biological fibers 14.
  • Appropriate fibers 14 of a biologically-derived component may include, but are not limited to, fibers of one or more ECM structural proteins, such as, for example, fibrin, collagen I, or elastin; one or more ECM signaling proteins, such as, for example, laminin, fibronectin, or collagen IV; one or more polysaccharides, such as, for example, hyaluronic acid, dextran, or alginate; one or more proteoglycans, such as, for example, glycosaminoglycans (GAGs) or chondroitin sulfate; or combinations thereof.
  • the biologically-derived material includes fibrinogen, fibrinogen converted to fibrin, type I collagen, or a combination thereof.
  • the biologically-derived material includes discrete micron- scale to millimeter-scale extruded biological fibers 14, where the fibers 14 are preferentially aligned in a predetermined direction.
  • the biologically-derived material includes mats of electrospun nanofibers, where the fibers 14 are preferentially aligned in a predetermined direction.
  • the predetermined direction is the axial direction of the PGS-infused hollow lumen vascular graft 10.
  • a 50/50 mixture 60 of the biologically-derived material and PGS is extruded using a core-shell technique into a hollow tube for construction of a hollow lumen composite vascular graft 10.
  • the 50/50 mixture 60 may be based on weight or based on volume.
  • the core die produces 5 -pm wide by 5-pm deep grooves along the inner lumen surface 22 of the PGS-infused biologically-derived materials to guide orientation of endothelial cells parallel to the direction of blood flow.
  • the graft 10 includes a predetermined thickness of the lumen wall 12, including any overbraid 18, and a predetermined lumen diameter.
  • the thickness of the lumen wall 12, including any overbraid 18, is in the range of about 10 pm to about 10 mm.
  • an appropriate thickness of the lumen wall 12 may be in the range of about 0.5 mm to about 1.5 mm.
  • an appropriate thickness of the lumen wall 12 may be in the range of about 0.25 mm to about 0.75 mm.
  • an appropriate lumen wall thickness may be on the thinner side of the range if the graft 10 is pre-seeded with cells or on the thicker side of the range for an acellular graft.
  • the graft 10 is a large-bore graft with a thickness of the lumen wall 12 in the range of about 1.5 mm to about 2.5 mm.
  • the lumen diameter is in the range of about 0.1 mm to about 10 mm.
  • orientation of the smooth muscle cells and other support cell types on the exterior lumen surface 20 of the hollow lumen composite vascular graft 10 is induced via a low braid angle multifilament overbraid 18 that provides both contour guidance to the cells and mechanical reinforcement for the vascular graft 10 during the early stages of implantation, especially in cases where an acellular graft 10 is implanted such that the graft 10 requires support until vascular cells infiltrate the graft 10 and provide support via ECM secretion.
  • the braid angle is in the range of about 30 degrees to about 130 degrees.
  • the overbraid 18 is made of a piezoelectric material, such as, for example, poly(vinylidene fluoride) (PVDF).
  • PVDF poly(vinylidene fluoride)
  • the overbraid is made of a yam of a polymeric material.
  • Appropriate polymeric materials for the yam may include, but are not limited to, polylactic acid thermoplastic (PLA), polyglycolide (PGA), poly L-lactic acid (PLLA), poly(lactic-co-glycolic acid) (PLGA), PGS, PGSU, polycaprolactone (PCL), 2-pyran-2-one-4,6-dicarboxylic acid (PDC), poly-p-dioxanone (PDO), polydioxanone (PDS), poly(l,8-octanediol citrate) (POC), collagen, a hybrid PGS-lactide or PGS-glycoside or PGS-mixed lactide-glycoside fiber chemistry, or combinations thereof.
  • the PGS-infused hollow lumen composite vascular graft 10 is pre-seeded with a patient’s own cells for cell therapy applications.
  • the PGS (including variants thereof) is loaded with one or more therapeutic agents for controlled release.
  • therapeutic agents may include, but are not limited to, antiplatelet drugs, including, but not limited to, cyclooxygenase inhibitors, adenosine diphosphate (ADP) receptor inhibitors, phosphodiesterase inhibitors, protease- activated receptor- 1 antagonists, adenosine reuptake inhibitors, or thromboxane inhibitors; healing and re-endothelization factors, including, but not limited to, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), platelet derived growth factor (PDGF), estradiols, or nitrous oxide compounds; anti inflammatory agents, including, but not limited to, sirolimus, tacrolimus, everolimus, leflunomide, m-prednisolone, dexamethasone
  • the hollow lumen composite vascular graft 10 includes alternating layers of the biologically-derived component and PGS, such as, for example, an inner extruded fibrin layer coated with PGS to reinforce.
  • the process includes selecting an extrudable PGS-infused formulation with variable material composition ratios that combine the best aspects of biologically-derived components and PGS. By adjusting this ratio, the longevity of the graft and cell attachment efficacy may be tuned. For example, an 80% fibrin/20% PGS ratio is expected to act as a glue for fibrin, limiting crack propagation and increasing the flexibility of the graft. Alternatively, a 20% fibrin/80% PGS formulation ratio is expected to behave much like an extruded PGS tube but with improved cell binding due to incorporation of fibrin domains.
  • the hollow lumen composite vascular graft 10 may be for either a small bore (e.g., annular diameter of 6 mm or less) or a large bore (e.g., annular diameter of greater than 6 mm) application.
  • the PGS-infused hollow lumen composite vascular graft 10 which may be acellular or cell-seeded, is sterilized and ready for implantation as an off-the-shelf- device.
  • a process includes implanting a PGS-infused hollow lumen composite vascular graft 10 into a subject in need thereof.
  • the biologically-derived material is fibrin, and the fibrin serves as a temporary scaffold helping to trigger a healing response while being enzymatically broken down as cells secrete a replacement extracellular matrix.
  • contour guidance is established in the lumen via extrusion or filling the void space between filaments with PGS, although a core-shell extrusion process may have a better potential for reproducibility.
  • the overbraiding of the hollow lumen composite vascular graft 10 to provide circumferential alignment to the exterior lumen surface 20 of the lumen wall 12 may be an optional feature, since the pulsatile flow through the hollow lumen 24 helps orient the exterior muscle cells without the presence of an overbraid 18.
  • the overbraid 18 is provided to align muscle cells more rapidly or to provide a secondary benefit, such as, for example, therapeutic release or electrical signaling.
  • the PGS is infused in its resinous form and left in resinous form in the graft. In other embodiments, the PGS is cured after being infused.
  • the PGS may be tuned, either based on the PGS structure or based on the addition of other components, such as, for example, therapeutic agents, to improve the properties and/or function of the hollow lumen composite vascular graft 10.
  • the PGS is infused with powdered biological component.
  • the PGS is infused into previously-generated structures using biological components, such as, for example, as a pore filling or as a space filler between filaments.
  • the PGS and/or the biologically-derived material are chemically crosslinked.
  • the vascular graft 10 has at least one bi-furcation or multi furcation to repair or replace a branching vessel.
  • Contour guidance may be established in any of a number of different ways, including, but not limited to, by a micropattemed die during extrusion forming a micropattem on a surface of the lumen wall, through incorporation of electrospun materials, through inclusion of braided structures, through inclusion of aligned hydrogel fiber sheets, through inclusion of multifilament fibers, through extrusion of PGS-containing fiber fragments that align with the flow of PGS coming out of the die upon extrusion, or combinations thereof
  • the hollow lumen composite vascular graft 10 is pre-seeded with vascular cells that deposit a layer of ECM on either the inner lumen surface or outer graft surface prior to the cells being removed.
  • the consistency and/or modulus of the composite is tuned by selectively crosslinking the bio-derived material to incorporate the PGS matrix 16 using a photo-initiated crosslinking mechanism.
  • a kind of interpenetrating or intermingled network of entrapped PGS is formed within the photo- crosslinked biologic material.
  • the selective crosslinking of the biologic material via photo crosslinking avoids the extensive inter and intra-polymer crosslinking of the PGS that would occur via thermal crosslinking.
  • This network arrangement is achieved by covalently anchoring or tethering a photoactive initiator species within the PGS polymer matrix 16 useful for subsequent photoinitiation (phototendering) to photo-crosslink the PGS-collagen (or PGS-other biologic) composite.
  • PGS lacks traditional ultraviolet (UV) absorbing functional groups that would compete for available UV radiation to initiate the crosslinking.
  • UV ultraviolet
  • PGS is essentially‘transparent’ to UV initiation making it a potential inert matrix.
  • additional structural stability is provided by crosslinking the biologic component while the native PGS functional groups still maintain thermal crosslink properties that are subsequently initiated, if desired.
  • the photoactive initiator species is a riboflavin-arginine system.
  • Riboflavin (vitamin B2) is a water-soluble vitamin necessary for the breakdown of carbohydrates, proteins and fats to produce energy from cellular respiration. Riboflavin is a co- factor in a number of essential cellular processes. Riboflavin has the following chemical structure that includes multiple OH tether groups:
  • riboflavin is involved in the electron transport chain, the production of pyridoxic acid from pyridoxal (vitamin B6) by pyridoxine 5'-phosphate oxidase, oxidation of pyruvate, a-ketoglutarate, and branched-chain amino acids, oxidation of fatty acids with acyl CoA dehydrogenase, conversion of retinol (vitamin A) to retinoic acid, and conversion of tryptophan to niacin (vitamin B3).
  • Arginine is an a-amino acid used in the biosynthesis of proteins, is important to the proliferation of endothelial cells in cell division and wound healing, and is a key nutrient to the immune system. Arginine is amphipathic, meaning it has both a hydrophilic and hydrophobic functional end. This feature provides arginine with a potential surface-active behavior. Arginine has the following chemical structure that includes a COOH tether group:
  • the photoactivity of the riboflavin-arginine system is based on an abstraction mechanism.
  • the riboflavin and arginine (or other components to form similar systems) is incorporated into the PGS via a water-mediated synthesis as described in U.S. 9,359,472 or other such receptive building-block composition of a water-mediated preparation for polycondensation.
  • a photosensitive dye such as, but not limited to riboflavin
  • a co-additive such as, but not limited to arginine
  • a biologic fiber/scaffold material such as, but not limited to collagen
  • the subsequent crosslinking may be properly classified as phototendering, but because it involves the acceleration of polymer breakdown and production of free radicals, it is sometimes more broadly considered photoinitiation.
  • the free radicals generated by the riboflavin and arginine are available for free radical photoactivity and photopolymerization or photocuring.
  • this system is initiated by photo-oxidation, which is different from a strict acrylated system that has a variety of drawbacks that make acrylated systems less desirable for biologic applications.
  • a phototendering system such as the riboflavin/arginine system provides a non-cytotoxic photo-initiation system for tissue engineering biologically compatible biopolymer, such as, for example, collagen, and synthetic bioresorbable polymer, such as, for example, PGS, as a photoinitiated system free of synthetic conventional photo-initiators.
  • tissue engineering biologically compatible biopolymer such as, for example, collagen
  • synthetic bioresorbable polymer such as, for example, PGS
  • PGS infusion may be applied to any graft including a hollow lumen, such as where PGS infusion provides advantageous mechanical or biological cues.
  • a hollow lumen composite vascular graft 10 may include, but are not limited to, as a scaffold for expansion of cells in a bioreactor, as the outer sheath of a nerve guidance conduit, as the core support scaffold for a lab-grown digit, such as, for example, a finger, as a small bore vascular graft, as a large bore vascular graft, or as a bifurcated structure.

Abstract

La présente invention concerne un procédé de formation d'une greffe vasculaire composite à lumière creuse qui comprend l'infusion d'une pluralité de fibres d'au moins un matériau d'origine biologique avec du poly(sébacate de glycérol) (PGS). Le procédé comprend en outre la formation d'une paroi luminale à partir de la pluralité de fibres et le PGS avec la pluralité de fibres étant orienté axialement dans la paroi luminale. Une greffe vasculaire composite à lumière creuse comprend une paroi luminale ayant une section transversale annulaire, une surface luminale interne et une surface luminale extérieure. La paroi luminale comprend une pluralité de fibres d'au moins un matériau d'origine biologique et une matrice de PGS imprégnant la pluralité de fibres. La pluralité de fibres sont orientées axialement dans la paroi luminale.
PCT/US2020/042454 2019-07-19 2020-07-17 Greffe composite à lumière creuse imprégnée de poly (sébacate de glycérol) WO2021016055A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201962876270P 2019-07-19 2019-07-19
US62/876,270 2019-07-19

Publications (1)

Publication Number Publication Date
WO2021016055A1 true WO2021016055A1 (fr) 2021-01-28

Family

ID=74194110

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2020/042454 WO2021016055A1 (fr) 2019-07-19 2020-07-17 Greffe composite à lumière creuse imprégnée de poly (sébacate de glycérol)

Country Status (1)

Country Link
WO (1) WO2021016055A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11957759B1 (en) 2022-09-07 2024-04-16 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993016687A1 (fr) * 1992-02-28 1993-09-02 Board Of Regents, The University Of Texas System Gels pour encapsulation de materiaux biologiques
US20010023370A1 (en) * 1999-07-02 2001-09-20 Scott Smith Composite vascular graft
US20070207186A1 (en) * 2006-03-04 2007-09-06 Scanlon John J Tear and abrasion resistant expanded material and reinforcement
US8192348B2 (en) * 2003-07-01 2012-06-05 Regents Of The University Of Minnesota Engineered blood vessels
WO2014074134A1 (fr) * 2012-11-09 2014-05-15 Tufts University Echafaudage de collagène multicouche
US20140309726A1 (en) * 2011-12-22 2014-10-16 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Biodegradable vascular grafts

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993016687A1 (fr) * 1992-02-28 1993-09-02 Board Of Regents, The University Of Texas System Gels pour encapsulation de materiaux biologiques
US20010023370A1 (en) * 1999-07-02 2001-09-20 Scott Smith Composite vascular graft
US8192348B2 (en) * 2003-07-01 2012-06-05 Regents Of The University Of Minnesota Engineered blood vessels
US20070207186A1 (en) * 2006-03-04 2007-09-06 Scanlon John J Tear and abrasion resistant expanded material and reinforcement
US20140309726A1 (en) * 2011-12-22 2014-10-16 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Biodegradable vascular grafts
WO2014074134A1 (fr) * 2012-11-09 2014-05-15 Tufts University Echafaudage de collagène multicouche

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11957759B1 (en) 2022-09-07 2024-04-16 Arvinas Operations, Inc. Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use

Similar Documents

Publication Publication Date Title
US20200179096A1 (en) Biodegradable vascular grafts
Goonoo et al. Polydioxanone-based bio-materials for tissue engineering and drug/gene delivery applications
JP4651280B2 (ja) 血管内人工器具用ｅｐｔｆｅ被覆材
US20200384159A1 (en) Electrospinning with sacrificial template for patterning fibrous constructs
Wen et al. Local delivery of dual microRNAs in trilayered electrospun grafts for vascular regeneration
JP5403613B2 (ja) ポリマーブレンド−バイオセラミック複合体製の埋込型医用デバイス
Arcaute et al. Fabrication of off-the-shelf multilumen poly (ethylene glycol) nerve guidance conduits using stereolithography
CN102065794B (zh) 经由管状浇铸工艺的支架制造方法
JP5294273B2 (ja) ポリマー−及びポリマーブレンド−バイオセラミック複合体製埋込み型医用デバイス
US6926735B2 (en) Multi-lumen vascular grafts having improved self-sealing properties
US5024671A (en) Microporous vascular graft
CN1972723A (zh) 用于血管成形术中的带有毫微纤维外层的气囊
US20150342764A1 (en) Bioabsorbable stents
US20100331947A1 (en) Inflatable Medical Device
JP2011525137A5 (fr)
WO2006044904A2 (fr) Elaboration a nano-echelle et a micro-echelle d'echafaudages polymeres pour l'elaboration de tissus vasculaires
JP2022079625A (ja) 生分解が管理された医療デバイス
WO2021016055A1 (fr) Greffe composite à lumière creuse imprégnée de poly (sébacate de glycérol)
KR102091840B1 (ko) 3차원 하이드로젤 적층 구조물, 및 이의 제조방법
CN1893990A (zh) 用于血管成形术的球囊
CN117179977B (zh) 一种全降解鼻窦药物支架及其制作方法
CN108619569A (zh) 负载微小核酸的三层人工血管电纺膜及其制备方法和应用
Pradhan-Nabzdyk Development of a Composite Electrospun Polyethylene Terephthalate-Polyglycolic Acid Material–Potential Use as a Drug-Eluting Vascular Graft

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20843014

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20843014

Country of ref document: EP

Kind code of ref document: A1