Rapid endothelialization of printed vascular grafts by perivascular niche-circulating endothelial progenitors crosstalk.

Successful regeneration of small-diameter vascular grafts requires rapid endothelialization to ensure patency. However, effectively recruiting circulating endothelial progenitor cells to achieve this remains a significant challenge. Here we show that accelerating the growth of adventitia into vascular grafts promotes fallout endothelialization on the blood-contacting surface. We engineered Micro-Nano structured Vascular Grafts (MnVGs) using high-resolution electrohydrodynamic (EHD) printing and electrostatic spinning. When implanted in rabbits, MnVGs rapidly regenerated neo-adventitia within the highly porous graft walls and achieved endothelialization as early as 2 weeks postoperatively, resulting in 90% patency rate (18/20). The regenerated arteries closely matched native vessels in structure and function. Mechanistically, we discovered that lymphatic endothelial cells enriched in the neoadventitia, were identified as the main contributors to the early recruitment of CD93+ ECs, which ultimately constituted the majority of the endothelium. Thus, MnVGs represent a potential strategy to preventing thrombosis in replacement of small caliber arteries.