Surface modification of polytetrafluoroethylene (PTFE) with a heparin-immobilized extracellular matrix (ECM) coating for small-diameter vascular grafts applications

Abstract

Intimal hyperplasia, thrombosis formation, and delayed endothelium regeneration are the main causes that restrict the clinical applications of PTFE small-diameter vascular grafts (inner diameter < 6 mm). An ideal strategy to solve such problems is to facilitate in situ endothelialization. Since the natural vascular endothelium adheres onto the basement membrane, which is a specialized form of extracellular matrix (ECM) secreted by endothelial cells (ECs) and smooth muscle cells (SMCs), functionalizing PTFE with an ECM coating was proposed. However, besides ECs, the ECM-modified PTFE improved SMC growth as well, thereby increasing the risk of intimal hyperplasia. In the present study, heparin was immobilized on the ECM coating at different densities (4.89 ± 1.02 μg/cm2, 7.24 ± 1.56 μg/cm2, 15.63 ± 2.45 μg/cm2, and 26.59 ± 3.48 μg/cm2), aiming to develop a bio-favorable environment that possessed excellent hemocompatibility and selectively inhibited SMC growth while promoting endothelialization. The results indicated that a low heparin density (4.89 ± 1.02 μg/cm2) was not enough to restrict platelet adhesion, whereas a high heparin density (26.59 ± 3.48 μg/cm2) resulted in decreased EC growth and enhanced SMC proliferation. Therefore, a heparin density at 7.24 ± 1.56 μg/cm2 was the optimal level in terms of antithrombogenicity, endothelialization, and SMC inhibition. Collectively, this study proposed a heparin-immobilized ECM coating to modify PTFE, offering a promising means to functionalize biomaterials for developing small-diameter vascular grafts.