Dual surface modification of poly(L-lactide) scaffold achieved by thermal incorporation of aligned nanofiber and click immobilization of VEGF to enhance endothelialization and blood compatibility

Abstract

Rapid endothelialization is very important in the development of blood-contact biomaterials because of the inhibitory effects of endothelium in preventing thrombosis and restenosis. In this study, topographical and biochemical cues were generated to accelerate endothelialization on the poly(L-lactide) (PLLA) scaffold via a simple, bio-orthogonal, and biocompatible process. Topographical guidance was incorporated into a PLLA scaffold via thermal attachment of aligned PLLA nanofibers using electrospinning. Vascular endothelial growth factor (VEGF) was covalently immobilized onto the PLLA scaffold by aminolysis and copper-catalyzed azide/alkyne cycloaddition-mediated click chemistry. Various surface analyses confirmed the presence of aligned topography and immobilized VEGF without delamination or leaching. In vitro experiments with human coronary artery endothelial cells revealed that proliferation, CD31 expression, and migration was significantly enhanced on the nanofiber-attached VEGF-immobilized PLLA scaffold. The aligned nanofiber also accommodated the sustained release of heparin, which suppressed the proliferation of human coronary artery smooth muscle cells and platelet activation without affecting surface endothelialization. The heparin-loaded, aligned, nanofiber-attached VEGF-immobilized PLLA scaffold was evidenced to be biocompatible and a promising candidate for blood-contact materials where fast endothelialization and suppressed platelet activation is required.