%A Yang,Sen %A Zheng,Xueni %A Qian,Meng %A Wang,He %A Wang,Fei %A Wei,Yongzhen %A Midgley,Adam C. %A He,Ju %A Tian,Hongyan %A Zhao,Qiang %D 2021 %J Frontiers in Bioengineering and Biotechnology %C %F %G English %K Small-diameter vascular grafts,Nitric Oxide,Vascular regeneration,vascular progenitor cells (VPCs),Vascular Calcification %Q %R 10.3389/fbioe.2021.770121 %W %L %M %P %7 %8 2021-November-30 %9 Original Research %# %! A NO-releasing vascular graft %* %< %T Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide %U https://www.frontiersin.org/articles/10.3389/fbioe.2021.770121 %V 9 %0 JOURNAL ARTICLE %@ 2296-4185 %X Artificial small-diameter vascular grafts (SDVG) fabricated from synthetic biodegradable polymers, such as poly(ε-caprolactone) (PCL), exhibit beneficial mechanical properties but are often faced with issues impacting their long-term graft success. Nitric oxide (NO) is an important physiological gasotransmitter with multiple roles in orchestrating vascular tissue function and regeneration. We fabricated a functional vascular graft by electrospinning of nitrate-functionalized poly(ε-caprolactone) that could release NO in a sustained manner via stepwise biotransformation in vivo. Nitrate-functionalized SDVG (PCL/NO) maintained patency following abdominal arterial replacement in rats. PCL/NO promoted cell infiltration at 3-months post-transplantation. In contrast, unmodified PCL SDVG showed slow cell in-growth and increased incidence of neointima formation. PCL/NO demonstrated improved endothelial cell (EC) alignment and luminal coverage, and more defined vascular smooth muscle cell (VSMC) layer, compared to unmodified PCL SDVG. In addition, release of NO stimulated Sca-1+ vascular progenitor cells (VPCs) to differentiate and contribute to rapid luminal endothelialization. Furthermore, PCL/NO inhibited the differentiation of VPCs into osteopontin-positive cells, thereby preventing vascular calcification. Overall, PCL/NO demonstrated enhanced cell ingrowth, EC monolayer formation and VSMC layer regeneration; whilst inhibiting calcified plaque formation. Our results suggested that PCL/NO could serve as promising candidates for improved and long-term success of SDVG implants.