| Current synthetic vascular grafts and polymer-coated drug-eluting stents (DES) have certain limitations, such as thrombosis and restenosis due to the incomplete recovery of vascular endothelial cells on their luminal sides. Surface modification of these materials is a viable method to enhance endothelialization. In this study, we proposed several strategies to modify poly(L-lactic acid) (PLLA), a promising material for vascular prostheses to enhance endothelialization on its surface. In the first approach, we modified the material surface with deposition of poly(vinylacetic acid) (PVAA) using plasma polymerization. PVAA films having different surface densities of --COOH groups or film thickness were created and characterized. Their effects on endothelial cell adhesion, proliferation, and function were studied. PVAA films with 9% -COOH surface density and 100 nm film thickness were found to be optimal for enhancing endothelialization. The mechanism for this enhancement might involve increased adsorption of fibronectin on its surface. In the second method, fibronectin was conjugated covalently with PVAA, which was deposited on PLLA, utilizing the rich --COOH of PVAA. Vascular Endothelial Growth Factor (VEGF) was subsequently conjugated with fibronectin for surface delivery of VEGF. Enhanced endothelial cells adhesion and proliferation was found on this modified PLLA surface, especially when VEGF receptor-genetically modified cells were used. Lastly, we coated PLLA with poly(1,8-octanediol-co-citrate) (POC)/poly(lactic-co-glycolic acid) (PLGA) microparticle composite. VEGF, fibroblast growth factor (FGF), and VEGF receptor plasmids were encapsulated in the PLGA microparticles for controlled release. Fibronectin and anti-CD34 antibody were, in turn, conjugated on top of POC to capture endothelial progenitor cells (EPC). It was found that the surface-modified PLLA successfully captured EPCs in a flowing condition, and rendered quick endothelialization on the surface. Using these strategies, enhanced endothelialization can be achieved on polymers such as PLLA, which naturally do not support endothelial cell growth, in order to reduce thrombosis and restenosis on vascular prostheses. |
