Biomimetic niche of vascular intima with biophysical orientation and biochemical stimulation for rapid endothelialization and long-term patency

Abstract

Clinical replacement of small-diameter vascular grafts (SDVG) for vessel lesion often encounters highly occluded risk due to acute platelet activation in a short run and poor endothelialization. Recent strategies built with either biochemical modification of heparinization or biophysical manipulation of hemodynamics have attempted to address the issue of unqualified long-term patency rate, but the major challenges on suppressing thrombosis and elevating fast endothelialization are yet untangled. Herein, we designed a biomimetic SDVG made of biochemical regulation of dopamine-mediated copper ion (DA-CuII) and biophysical regulation of intimal oriented nanotopography. The DA-CuII system can significantly modulate the cell fates of vascular cells containing platelets, endothelial cells, and smooth muscle cells via catalytically producing nitric oxide (NO) in situ and the intimal oriented nanotopography can effectively promote the oriented growth and elongation of endothelial cells to achieve luminal remodeling and maintain an instructive long-term patency. Consequently, the current work integrates biochemical cue of NO signaling molecule with biophysical stimulation of intimal oriented nanotopography to create an off-the-shelf SDVG with specific anti-thrombosis and rapid endothelialization.