Hydrogen sulfide releasing and carboxybetaine modified vascular graft with enhanced anticoagulant, anticalcification, and pro-endothelialization properties

Abstract

In the cardiovascular system, hydrogen sulfide(H2S) gasotransmitter regulates physiological processes involved in vasorelaxation, cardioprotection, anti-inflammation, and anti-oxidation. In this study, H2S releasing and carboxybetaine modified vascular graft with enhanced anticoagulant, anticalcification, and pro-endothelialization properties was designed and fabricated to meet the demand for small-diameter vascular grafts. Initially, a keratin-based bio-macromolecular donor of H2S was synthesized and then coelectrospun with polycaprolactone(PCL) to afford nanofibrous mats. Next, zwitterionic carboxybetaine was immobilized through dopamine self-polymerization to prolong the release of H2S, improve blood compatibility, and reduce calcification effectively. The biocomposite mats performed cell selectivity by promoting the adhesion and migration of HUVECs while inhibiting the proliferation of HUASMCs. Furthermore, the mats showed an excellent ability to resist oxidative stress. The results of the 3D perfusion culture proved that the grafts could promote endothelium formation under shear force. In vivo implantation results suggested that these grafts were capable of facilitating rapid endothelialization and reducing calcification.