Small Diameter Vascular Graft Produced by a Hybrid Method

Abstract

The present invention relates to a hybrid graft and methods of generating the hybrid graft. The hybrid graft comprises an exterior surface and a luminal surface. The luminal surface comprises a micropattern of grooves to which cells adhere and orient along. The exterior surface comprises electrospun microfibers wherein the microfibers provide mechanical properties to the graft. The hybrid graft is capable supporting endothelial cell attachment, endothelial cell alignment, cell proliferation, and maintaining their in vivo function. The graft of the invention can recapitulate the in vivo morphology and function of natural vascular endothelium.

1 - 9 . (canceled) 
     
     
         10 . A method of making a hybrid graft, the method comprising generating a micropatterned luminal surface by electrocasting/electrospraying a first elastomeric polymer on a micropatterned mandrel thereby generating a casted graft, followed by electrospinning a second elastomeric polymer on the casted graft to produce electrospun fibers on the exterior surface of the graft. 
     
     
         11 . The method of  claim 10 , wherein the first elastomeric polymer and second elastomeric polymer are cholesterol modified polyurethane. 
     
     
         12 . The method of  claim 10 , wherein the micropatterned luminal surface comprises grooves to which cells adhere and orient along, wherein each groove has a depth of about 1 μm and a width of about 5 μm, and each groove is positioned about 5 μm apart from each other. 
     
     
         13 - 19 . (canceled) 
     
     
         20 . The method of  claim 10 , wherein the hybrid graft is a vascular graft. 
     
     
         21 . The method of  claim 10 , wherein the first elastomeric polymer is selected from the group consisting of poly-(D,L-lactide-co-glycolide) (PLGA), poly-(dimethylsiloxane) (PDMS), poly-(L-lactide-co-caprolactone-co-glycolide) (PLCG), polycaprolactone (PCL), polylactic acid (PLA), polystyrene, polyurethane, polytetrafluoroethylene (ePTFE), and tetraphthlate (Dacron). 
     
     
         22 . The method of  claim 10 , wherein the second elastomeric polymer is selected from the group consisting of poly-(D,L-lactide-co-glycolide) (PLGA), poly-(dimethylsiloxane) (PDMS), poly-(L-lactide-co-caprolactone-co-glycolide) (PLCG), polycaprolactone (PCL), polylactic acid (PLA), polystyrene, polyurethane, polytetrafluoroethylene (ePTFE), and tetraphthlate (Dacron). 
     
     
         23 . The method of  claim 12 , wherein the cells are selected from the group consisting of chondroblasts, chondrocytes, fibroblasts, endothelial cells, osteoblasts, osteocytes, epithelial cells, epidermal cells, mesenchymal cells, hematopoietic cells, nerve cells, Schwann cells, glial cells, stem cells, dorsal cool ganglia, and combinations thereof. 
     
     
         24 . The method of  claim 10 , wherein the second elastomeric polymer is electrospun as a solution or suspension in a solvent; wherein the solvent is selected from the group consisting of water, 2,2,2-trifluoroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, urea, monochloroacetic acid, acetamide, N-methylformamide, N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), dimethylacetamide, N-methyl pyrrolidone (NMP), acetic acid, trifluoroacetic acid, ethyl acetate, acetonitrile, trifluoroacetic anhydride, 1,1,1-trifluoroacetone, maleic acid, hexafluoroacetone, tetrahydrofuran (THF) or combinations thereof. 
     
     
         25 . The method of  claim 10 , wherein the first elastomeric polymer and the second elastomeric polymer are cholesterol modified polyurethane; wherein the second elastomeric polymer is electrospun as a solution or suspension of tetrahydrofuran (THF).