Multi-Layered Graft for Tissue Engineering Applications

Abstract

A multi-layer device is provided that is useful in tissue regeneration, for example, for vascular regeneration, e.g., for use in treatment of a coronary vascular disease, such as for treatment of myocardial infarction. A method of making the device also is provided.

1 . A method of making a synthetic tubular graft device, comprising:
 depositing an ECM gel layer over a first tubular, porous, biodegradable polymer matrix; and   depositing a second tubular, porous, biodegradable polymer matrix over the ECM gel to produce a tubular structure.   
     
     
         2 . The method of  claim 1 , wherein the first tubular, porous, biodegradable polymer matrix is a dry-electrospun matrix. 
     
     
         3 . The method of  claim 1 , wherein the ECM gel is prepared from vascular tissue. 
     
     
         4 . The method of  claim 1 , wherein the second tubular, porous, biodegradable polymer matrix is prepared by phase separation. 
     
     
         5 . The method of  claim 1 , wherein the first tubular, porous, biodegradable polymer matrix and/or the second tubular, porous, biodegradable polymer matrix comprises one or more of: poly(lactic acid) (PLA); poly(trimethylene carbonate) (PTMC); poly(caprolactone) (PCL); poly(glycolic acid) (PGA); poly(glycolide-co-trimethylenecarbonate) (PGTMC); poly(L-lactide-co-glycolide) (PLGA); polyethylene-glycol (PEG-) containing block copolymers; polyphosphazene; poly(ester urethane) urea (PEUU); poly(ether ester urethane)urea (PEEUU); poly(ester carbonate)urethane urea (PECUU); poly(carbonate)urethane urea (PCUU); a polyurethane; a polyester; a polymer comprising monomers derived from alpha-hydroxy acids such as: polylactide, poly(lactide-co-glycolide), poly(L-lactide-co-caprolactone), polyglycolic acid, poly(dl-lactide-co-glycolide), and/or poly(-lactide-co-dl-lactide); a polymer comprising monomers derived from esters including polyhydroxybutyrate, polyhydroxyvalerate, polydioxanone, and/or polyglactin; a polymer comprising monomers derived from lactones; or a polymer comprising monomers derived from carbonates including polycarbonate, polyglyconate, poly(glycolide-co-trimethylene carbonate), or poly(glycolide-co-trimethylene carbonate-co-dioxanone). 
     
     
         6 . The method of  claim 1 , comprising:
 dry electrospinning a poly(ester urethane) urea onto a mandrel to form the first tubular, porous, biodegradable polymer matrix;   placing the mandrel comprising the first tubular, porous, biodegradable polymer matrix within a cylindrical mold having an inside diameter greater than an outside diameter of the first tubular, porous, biodegradable polymer matrix;   depositing an ECM pre-gel about the first tubular, porous, biodegradable polymer matrix;   gelling the ECM pre-gel about the first tubular, porous, biodegradable polymer matrix; and   inserting the ECM gel-coated first tubular, porous, biodegradable polymer matrix into a tube of a porous poly(ester urethane) urea matrix.   
     
     
         7 . The method of  claim 1 , wherein:
 the first tubular, porous, biodegradable polymer matrix has an inner diameter of from 1 mm to 2 mm;   the device has a wall thickness of from 200 μm to 1 mm;   the thickness of the combined layers of the first tubular, porous, biodegradable polymer matrix plus the ECM gel ranges from 100 μm to 500 μm; or   the thickness of the second tubular, porous, biodegradable polymer matrix plus the ECM gel ranges from 50 μm to 250 μm.   
     
     
         8 . The method of  claim 1 , wherein either or both of the first tubular, porous, biodegradable polymer matrix and the second tubular, porous, biodegradable polymer matrix comprises an anti-thrombogenic polymer composition. 
     
     
         9 . A multi-layer synthetic graft device comprising:
 a first porous, biodegradable polymer matrix;   an ECM gel layer over the first porous, biodegradable polymer matrix; and   a second porous, biodegradable polymer matrix over the ECM gel.   
     
     
         10 . The device of  claim 9 , comprising:
 a first tubular, porous, biodegradable polymer matrix;   an ECM gel layer disposed circumferentially about the first tubular, porous, biodegradable polymer matrix; and   a second tubular, porous, biodegradable polymer matrix disposed circumferentially about the ECM gel,   wherein the first tubular, porous, biodegradable polymer matrix is optionally a dry-electrospun matrix.   
     
     
         11 . The device of  claim 9 , wherein the ECM gel is prepared from vascular tissue. 
     
     
         12 . The device of  claim 9 , wherein the second tubular, porous, biodegradable polymer matrix is prepared by thermally induced phase separation. 
     
     
         13 . The device of  claim 9 , wherein the first tubular, porous, biodegradable polymer matrix, and/or the second tubular, porous, biodegradable polymer matrix comprises one or more of: poly(lactic acid) (PLA); poly(trimethylene carbonate) (PTMC); poly(caprolactone) (PCL); poly(glycolic acid) (PGA); poly(glycolide-co-trimethylenecarbonate) (PGTMC); poly(L-lactide-co-glycolide) (PLGA); polyethylene-glycol (PEG-) containing block copolymers; polyphosphazene; poly(ester urethane) urea (PEUU); poly(ether ester urethane)urea (PEEUU); poly(ester carbonate)urethane urea (PECUU); poly(carbonate)urethane urea (PCUU); a polyurethane; a polyester; a polymer comprising monomers derived from alpha-hydroxy acids such as: polylactide, poly(lactide-co-glycolide), poly(L-lactide-co-caprolactone), polyglycolic acid, poly(dl-lactide-co-glycolide), and/or poly(l-lactide-co-dl-lactide); a polymer comprising monomers derived from esters including polyhydroxybutyrate, polyhydroxyvalerate, polydioxanone, and/or polyglactin; a polymer comprising monomers derived from lactones; or a polymer comprising monomers derived from carbonates including polycarbonate, polyglyconate, poly(glycolide-co-trimethylene carbonate), or poly(glycolide-co-trimethylene carbonate-co-dioxanone). 
     
     
         14 . The device of  claim 9 , wherein:
 the first tubular, porous, biodegradable polymer matrix has an inner diameter ranging from 1 mm to 2 mm;   the device has a wall thickness of from 200 μm to 1 mm;   the thickness of the combined layers of the first tubular, porous, biodegradable polymer matrix plus the ECM gel ranges from 100 μm to 500 μm; or   the thickness of the second tubular, porous, biodegradable polymer matrix plus the ECM gel ranges from 50 μm to 250 μm.   
     
     
         15 . The device of  claim 9 , wherein either or both of the first tubular, porous, biodegradable polymer matrix and the second tubular, porous, biodegradable polymer matrix comprises an anti-thrombogenic polymer composition. 
     
     
         16 . A method of producing, repairing or replacing a tissue in a patient, comprising implanting in the patient the device of  claim 9  in the patient. 
     
     
         17 . The method of  claim 16 , wherein the device is tubular and/or is anastamosed to a blood vessel of the patient. 
     
     
         18 - 19 . (canceled) 
     
     
         20 . The method of  claim 16 , wherein the patient is suffering from an ischemic event. 
     
     
         21 . The method of  claim 20 , wherein the ischemic event is a coronary artery disease, and the device is anastamosed to a coronary artery. 
     
     
         22 . A kit comprising the device according to  claim 9  in suitable packaging, such as a foil and/or plastic pouch or container, such as a Mylar package.