Fabrication and characterization of polymeric devices for synthetic small diameter vascular graft, controlled release, and tissue engineering applications

Small diameter vascular grafts (SDVGs) engineered with suitable pore and mechanical properties and the ability to release therapeutics may improve healing responses, suppress anastomotic neointimal hyperplasia (ANH), and lead to increased SDVG patency. In this study, phase separation behavior of polymer solutions is utilized to fabricate: (1) polyurethane SDVGs with optimum pore and mechanical properties; (2) heparin-loaded controlled release systems for incorporation within polyurethane SDVGs to create drug eluting SDVGs; and (3) drug-loaded porous devices to serve as vascular grafts and/or scaffolds for tissue engineering applications. The SPI technique was optimized to fabricate highly porous Carbothane SDVGs by using low Carbothane concentrations and 100% tetrahydrofuran as a solvent. Confocal microscopy was used to measure SDVG porosity and visualize the graft pore network. SDVGs were fabricated with coaxial layers of two Carbothane resins with different mechanical properties. The elastic moduli of these grafts were shown to approach that of rat aortas in low strain regions. Heparin-loaded controlled release systems were developed to incorporate within the walls of SDVGs to create drug eluting SDVGs. Heparin-loaded PLGA microspheres were fabricated via the solvent removal method with low initial burst and release until the third week. Heparin-loaded polymeric membranes (i.e. melt-extruded EVAc rods, polycaprolactone (PCL), and Carbothane films, and Carbothane membranes) were fabricated using wet and dry casting methods. Much of the delivery systems, however, exhibited an unacceptable initial burst of heparin. In vivo pilot studies showed that Carbothane SDVGS are suitable for implantation as there was no evidence of aneurysm formation or weak areas in the explants up to 16 weeks. Two techniques were developed to fabricate porous constructs to serve as vascular grafts and/or scaffolds for tissue engineering. Porous constructs composed of cylindrical microfibers with diameters of less than 5 mum were fabricated using a novel solvent removal method. Heparin was encapsulated within the microfibers with high encapsulation efficiency. Porous PCL films were fabricated using a dry casting method in which porosity was induced using non-volatile non-solvents that were miscible with the solvent. Porosity was controlled by the use of different compositions of non-solvent and varying polymer concentration.