Facile fabrication of copper-incorporating poly(ε-caprolactone)/keratin mats for tissue-engineered vascular grafts with the potential of catalytic nitric oxide generation

Abstract

Tissue-engineered vascular grafts (TEVGs) provide a new alternative for vascular construction. Nitric oxide (NO) is capable of promoting vascular tissue regeneration and reducing restenosis caused by vascular implantation. Therefore, in situ production of NO by catalytic decomposition of the endogenous donor is a promising strategy to fabricate a TEVG. In this study, poly(ε-caprolactone) (PCL) was first electrospun with keratin (Ker) to afford PCL/Ker mats and then incorporated with Cu(II) ions through multiple interactions. This strategy is very simple, green, and facile. Particularly, the incorporated Cu(II) ions were partially reduced to Cu(I) ions due to the reducibility of keratin. The chelated copper ions were expected to catalyze the generation of NO from endogenous S-nitrosothiol (RSNO). As a result, PCL/Ker-Cu mats selectively accelerated the adhesion, migration, and growth of human umbilical vein endothelial cells (HUVECs), while inhibiting the proliferation of human umbilical artery smooth muscle cells (HUASMCs). Furthermore, these mats exhibited excellent blood compatibility and significant antibacterial activity. Vascular implantation in vivo indicated that the tubular mats could inhibit thrombus formation and retain patency for 3 months after implantation in the rabbit carotid artery. More importantly, vascular remodeling was observed during follow-up, including a complete endothelium and smooth muscle layer. Taken together, the PCL/Ker-Cu mats have great potential application in vascular tissue regeneration.