Reinforced tissue graft

Abstract

A biocompatible tissue graft includes a first layer of a bioremodelable collageneous material, a second layer of biocompatible synthetic or natural remodelable or substantially remodelable material attached to the first layer; and at least one fiber that is stitched in a reinforcing pattern in the first layer and/or second layer to mitigate tearing and/or improve fixation retention of the graft, and substantially maintain the improved properties while one or more of the layers is remodeling.

Having described the invention, the following is claimed: 
     
         1 . A biocompatible tissue graft comprising:
 a first layer of a bioremodelable collageneous material;   a second layer of biocompatible synthetic or natural remodelable or substantially remodelable material attached to the first layer; and   at least one fiber that is stitched in a reinforcing pattern in the first layer and/or second layer to mitigate tearing and/or improve fixation retention of the layers, and substantially maintain the improved properties while one or more of the layers is remodeling.   
     
     
         2 . The tissue graft of  claim 1 , the first layer comprising extracellular matrix and the at least one fiber reinforcing the extracellular matrix. 
     
     
         3 . The tissue graft of  claim 2 , the second layer comprising extracellular matrix. 
     
     
         4 . The tissue graft of  claim 1 , wherein the second layer comprising a biocompatible substantially remodelable synthetic material. 
     
     
         5 . The tissue graft of  claim 4 , wherein the second layer comprises a mesh of synthetic material. 
     
     
         6 . The tissue graft of  claim 1 , wherein the fiber comprises a natural or synthetic material. 
     
     
         7 . The tissue graft of  claim 6 , wherein the first layer comprises a mammalian-derived or plant-based collagen material. 
     
     
         8 . The tissue graft of  claim 6 , wherein the fiber is selected from the group consisting of collagen, silk, sericin free silk, modified silk fibroins, polyesters like PGA, PLA, polylactic-co-glycolic acid (PLGA), polyethyleneglycol (PEG), polyhydroxyalkanoates (PHA), polyethylene terephthalate (PET), polyethylene (PE), ultra-high molecular weight polyethylene (UHMWPE), blends thereof, and copolymers thereof. 
     
     
         9 . The tissue graft of  claim 6 , wherein at least one of the first layer, the second layer, and the fiber is modified to improve adhesion between the layers and the fiber. 
     
     
         10 . The tissue graft of  claim 1 , wherein the fibers are stitched into the layers in a concentric pattern. 
     
     
         11 . The tissue graft of  claim 11 , the at least one fiber having at least one free end extending beyond a peripheral surface of the tissue graft for securing the tissue graft to a host tissue. 
     
     
         12 . The tissue graft of  claim 2 , wherein the extracellular matrix is decellularized. 
     
     
         13 . The tissue graft of  claim 1 , wherein at least one the first layer or the second layer further comprises at least one differentiated or progenitor cell. 
     
     
         14 . The tissue graft of  claim 1 , wherein at least one of the first layer or the second layer further comprises at least one biologically active molecule selected from the group consisting of drugs, sclerosing agents, enzymes, hormones, cytokines, colony-stimulating factors, vaccine antigens, antibodies, clotting factors, angiogenesis factors, regulatory proteins, transcription factors, receptors, structural proteins, nucleic acid therapeutic agents, and combinations thereof. 
     
     
         15 . A biocompatible tissue graft comprising:
 a first layer of a bioremodelable collageneous material;   a second layer of biocompatible synthetic or natural remodelable or substantially remodelable material attached to the first layer; and   at least one fiber stitched in a reinforcing pattern in the first layer and/or second layer to mitigate tearing of the graft, improve fixation retention of the graft, and/or limit cyclic stretching of the graft, and substantially maintain these properties following partial enzymatic degradation of the graft while one or more of its layers remodels, the at least one fiber having at least one free end extending beyond a peripheral surface of the tissue graft for securing the tissue graft to a host tissue.   
     
     
         16 . The tissue graft of  claim 15 , wherein the at least one fiber extends at a non-perpendicular angle to the peripheral surface of the graft. 
     
     
         17 . The tissue graft of  claim 15 , wherein the at least one fiber extends beyond opposing peripheral surfaces of the graft. 
     
     
         18 . The tissue graft of  claim 15 , wherein the at least one fiber comprises a first fiber that extends beyond a first pair of opposing peripheral surfaces and a second fiber that extends beyond a second pair of opposing peripheral surfaces different from the first pair. 
     
     
         19 . The tissue graft of  claim 15 , wherein the fiber comprises a biocompatible material that is bioresorbable, biodegradable, or non-resorbable. 
     
     
         20 . The tissue graft of  claim 15 , wherein at least one of the first layer, the second layer, and the fiber is modified to improve adhesion between the layers and the fiber. 
     
     
         21 . The tissue graft of  claim 15 , wherein the at least one fiber is stitched into at least one of the first layer or the second layer in a cross-hatched configuration. 
     
     
         22 . The tissue graft of  claim 15 , wherein the at least one fiber is stitched into at least one of the first layer or second layer in a concentric pattern. 
     
     
         23 . The tissue graft of  claim 15 , wherein the at least one fiber is stitched into at least one of the first layer or second layer in multiple concentric patterns. 
     
     
         24 . The tissue graft of  claim 15 , wherein the at least one fiber comprises fibers stitched into at least one of the first layer or second layer in a linear pattern. 
     
     
         25 . The tissue graft of  claim 15 , wherein at least one of the first layer and the second layer is decellularized. 
     
     
         26 . The tissue graft of  claim 15 , wherein at least one the first layer and the second layer further comprises at least one differentiated or progenitor cell. 
     
     
         27 . The tissue graft of  claim 15 , wherein at least one of the first layer and the second layer further comprises at least one biologically active molecule selected from the group consisting of drugs, sclerosing agents, enzymes, hormones, cytokines, colony-stimulating factors, vaccine antigens, antibodies, clotting factors, angiogenesis factors, regulatory proteins, transcription factors, receptors, structural proteins, nucleic acid therapeutic agents, and combinations thereof. 
     
     
         28 . The tissue graft of  claim 15 , the first layer comprising an extracellular matrix and the at least one fiber reinforcing the extracellular matrix. 
     
     
         29 . The tissue graft of  claim 28 , the second layer comprising extracellular matrix. 
     
     
         30 . The tissue graft of  claim 28 , wherein the extracellular matrix is decellularized. 
     
     
         31 . The tissue graft of  claim 15 , wherein the second layer comprising a biocompatible substantially remodelable synthetic material. 
     
     
         32 . The tissue graft of  claim 31 , wherein the second layer comprises a mesh of synthetic material. 
     
     
         33 . The tissue graft of  claim 15 , wherein the fiber comprises a natural or synthetic material. 
     
     
         34 . The tissue graft of  claim 15 , wherein the first layer comprises a mammalian-derived or plant-based collagen material. 
     
     
         35 . The tissue graft of  claim 15 , wherein the at least one fiber is radio-opaque to allow the location, integrity, and/or deformation of the tissue graft to be assessed in a living system.