Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide.
Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide.
复制标题
硝酸盐功能化聚（ε-己内酯）小直径血管移植物通过持续释放一氧化氮增强血管再生
DOI：
10.3389/fbioe.2021.770121
复制
发表时间：
2021
影响因子：
5.7
通讯作者：
Zhao Q
中科院分区：
文献类型：
--
作者：
Yang S;Zheng X;Qian M;Wang H;Wang F;Wei Y;Midgley AC;He J;Tian H;Zhao Q
人工小直径血管移植物（SDVG）由合成的可生物降解聚合物，如聚（ε-己内酯）（PCL）制成，具有良好的力学性能，但经常面临影响其长期移植成功的问题。一氧化氮（NO）是一种重要的生理气体递质，在协调血管组织功能和再生中起着多种作用。本研究采用静电纺丝法制备了硝酸盐功能化聚（ε-己内酯）血管移植物，该血管移植物能在体内通过分步生物转化持续释放一氧化氮。硝酸化SDVG （PCL/NO）维持大鼠腹动脉置换术后的通畅。PCL/NO促进移植后3个月细胞浸润。相比之下，未经修饰的PCL SDVG显示细胞生长缓慢，新内膜形成的发生率增加。与未修饰的PCL SDVG相比，PCL/NO表现出更好的内皮细胞（EC）排列和管腔覆盖，更明确的血管平滑肌细胞（VSMC）层。此外，NO的释放刺激Sca-1+血管祖细胞（VPCs）分化并促进快速腔内内皮化。此外，PCL/NO抑制VPCs向骨桥蛋白阳性细胞的分化，从而防止血管钙化。总体而言，PCL/NO可促进细胞向内生长、EC单层形成和VSMC层再生；同时抑制钙化斑块的形成。我们的研究结果表明，PCL/NO可以作为改善和长期成功的SDVG植入物的有希望的候选者。
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.
登录
查看更多内容
影响因子：
9.7
作者：
Nie, Yan;Zhang, Kaiyue;Li, Zongjin
通讯作者：
Li, Zongjin
影响因子：
82.9
作者：
Aicher, A;Heeschen, C;Dimmeler, S
通讯作者：
Dimmeler, S
影响因子：
4.6
作者：
Hadinata, Ignatius E.;Hayward, Philip A. R.;Buxton, Brian F.
通讯作者：
Buxton, Brian F.
影响因子：
9.8
作者：
Cho HJ;Cho HJ;Lee HJ;Song MK;Seo JY;Bae YH;Kim JY;Lee HY;Lee W;Koo BK;Oh BH;Park YB;Kim HS
通讯作者：
Kim HS
影响因子：
9.7
作者：
Kabirian, Fatemeh;Milan, Peiman Brouki;Mozafari, Masoud
通讯作者：
Mozafari, Masoud