Electrospinning of Resorbable Amino-Acid Based Poly(Ester Urea)s for Regenerative Medicin

Electrospinning generates very fine fibers with diameters that bridge nanometer to micrometer length scales and loosely connected 3D fibrous structure which can mimic native extracellular matrix (ECM). Some other advantages of electrospun nanofibers include high surface area per unit mass, variety of surface functionalization strategies, simplicity of process, and tunable morphology. These advantages make electrospun nanofibers very attractive candidate for regenerative medicine applications, such as tissue engineering and drug delivery. Degradable polymers, including PCL, PLA, PGA and their copolymers or blends are the most commonly known and used materials to fabricate electrospun scaffolds for regenerative medicine. However, these materials are limited in that they create acidic degradation byproducts that cause inflammation and cell phenotypes changes in surrounding tissues. In the first part of this work, a new class of resorbable L-leucine based poly(ester urea)s (PEUs) was developed by interfacial polymerization. The chemical, thermal and mechanical properties of the resulting polymers were characterized. This new class of PEUs showed wider tunable range of thermal, mechanical and degradation properties than most commonly studied degradable polymers. The in vitro hydrolytic degradation study indicated the PEU polymers are degradable and it did not cause significant pH drop during the degradation process. The protein adsorption study showed this kind of materials had PRP blocking effect after pre-adsorbing fibrinogen. Vascular cells, such as smooth muscle cells and endothelia cells, were found to be able to spread and attach on the PEU polymer film. Taken together, the data suggest the new PEUs are promising candidates for vascular tissue engineering.;As a continuous work to explore the application of PEUs in vascular tissue engineering, small diameter vascular grafts with 1 mm diameter were fabricated using electrospinning. Long term performance of two types of PEU grafts with different wall thickness (type A: 250 mum; type B: 350 mum) were evaluated in an abdominal infra-renal aortic mouse model over 1 year. Significantly, the small diameter vascular grafts did not rupture or lead to acute thrombogenic events in the intervals tested. The pilot study in vivo showed long term patency and extensive tissue remodeling with type A grafts, while the type B grafts experienced occlusion over the 1 year interval due to intimal hyperplasia. This study affords significant findings that will guide the design of future generations of small diameter vascular grafts.;In the third part of my doctoral research, the application of electrospun PEU scaffold in protein drug delivery was explored. Recombinant human growth hormone (rhGH) for protein therapeutics is in great demand. However, as a consequence of short half-life, it is still quite a challenge to develop effective rhGH sustained delivery systems that can exceed a month in duration. In this part, a new sustained release strategy of rhGH was developed by encapsulating sugar glass nanoparticle protected rhGH in the electrospun PEU nanofibers. The protein was found to be randomly dispersed throughout the electrospun fibers in an aggregate form. Sustained rhGH release with modest burst release was observed for up to 6 weeks in vitro as confirmed by protein assay. These results clearly suggest the feasibility of using electrospun PEU nanofibers as new, long-term sustained release strategy for rhGH.