Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide

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 gas...

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Autores principales:	Sen Yang, Xueni Zheng, Meng Qian, He Wang, Fei Wang, Yongzhen Wei, Adam C. Midgley, Ju He, Hongyan Tian, Qiang Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	small-diameter vascular grafts nitric oxide vascular regeneration vascular progenitor cells (VPCs) vascular calcification Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/5c70c860b22f488ab4aa428f35d58ed8
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spelling	oai:doaj.org-article:5c70c860b22f488ab4aa428f35d58ed82021-12-01T20:05:07ZNitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide2296-418510.3389/fbioe.2021.770121https://doaj.org/article/5c70c860b22f488ab4aa428f35d58ed82021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.770121/fullhttps://doaj.org/toc/2296-4185Artificial 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.Sen YangSen YangXueni ZhengXueni ZhengMeng QianMeng QianHe WangHe WangFei WangFei WangYongzhen WeiYongzhen WeiAdam C. MidgleyAdam C. MidgleyJu HeHongyan TianQiang ZhaoQiang ZhaoQiang ZhaoFrontiers Media S.A.articlesmall-diameter vascular graftsnitric oxidevascular regenerationvascular progenitor cells (VPCs)vascular calcificationBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	small-diameter vascular grafts nitric oxide vascular regeneration vascular progenitor cells (VPCs) vascular calcification Biotechnology TP248.13-248.65
spellingShingle	small-diameter vascular grafts nitric oxide vascular regeneration vascular progenitor cells (VPCs) vascular calcification Biotechnology TP248.13-248.65 Sen Yang Sen Yang Xueni Zheng Xueni Zheng Meng Qian Meng Qian He Wang He Wang Fei Wang Fei Wang Yongzhen Wei Yongzhen Wei Adam C. Midgley Adam C. Midgley Ju He Hongyan Tian Qiang Zhao Qiang Zhao Qiang Zhao Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide
description	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.
format	article
author	Sen Yang Sen Yang Xueni Zheng Xueni Zheng Meng Qian Meng Qian He Wang He Wang Fei Wang Fei Wang Yongzhen Wei Yongzhen Wei Adam C. Midgley Adam C. Midgley Ju He Hongyan Tian Qiang Zhao Qiang Zhao Qiang Zhao
author_facet	Sen Yang Sen Yang Xueni Zheng Xueni Zheng Meng Qian Meng Qian He Wang He Wang Fei Wang Fei Wang Yongzhen Wei Yongzhen Wei Adam C. Midgley Adam C. Midgley Ju He Hongyan Tian Qiang Zhao Qiang Zhao Qiang Zhao
author_sort	Sen Yang
title	Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide
title_short	Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide
title_full	Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide
title_fullStr	Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide
title_full_unstemmed	Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide
title_sort	nitrate-functionalized poly(ε-caprolactone) small-diameter vascular grafts enhance vascular regeneration via sustained release of nitric oxide
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5c70c860b22f488ab4aa428f35d58ed8
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Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide

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