Hyaluronan promotes the regeneration of vascular smooth muscle with potent contractile function in rapidly biodegradable vascular grafts
Hyaluronan promotes the regeneration of vascular smooth muscle with potent contractile function in rapidly biodegradable vascular grafts
复制标题
透明质酸促进可快速生物降解的血管移植物中具有强大收缩功能的血管平滑肌的再生
DOI：
10.1016/j.biomaterials.2020.120226
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发表时间：
2020-10-01
期刊：
影响因子：
14
通讯作者：
Zhao, Qiang
中科院分区：
文献类型：
--
作者：
Qin, Kang;Wang, Fei;Zhao, Qiang
具有生理功能的平滑肌再生一直是血管组织工程的关键挑战。透明质酸（HA）作为细胞外基质的主要成分，在调节组织损伤和修复中起着重要作用。在这项研究中，仿生血管移植物的合成可降解聚合物和天然ECM成分，包括胶原蛋白I型以及低和高分子量HA（低分子量HA和高分子量HA）的共静电纺丝制备。植入大鼠腹主动脉后，移植物表现出持续的HA释放，有效地增强了血管平滑肌的再生。此外，与其他组相比，负载LMW HA的血管移植物表现出快速内皮化。更重要的是，HA负载的聚（L-丙交酯-共-己内酯）移植物表现出最佳的血管介质层，伴随着组织良好的弹性蛋白纤维长期植入（6个月）后，他们保持强大的生理功能高达1/3的原生动脉。相比之下，由于缓慢降解限制再生，在聚（ε-己内酯）移植物中观察到平滑肌再生不足。其机制进一步研究和解释的HA诱导的平滑肌细胞（SMC）的迁移通过CD 44介导的信号。此外，低分子量HA可促进血管祖细胞迁移，并进一步分化为SMC。这些结果突出了HA在功能性血管平滑肌再生中的重要性，并通过结合快速降解的聚合物和具有巨大转化潜力的生物活性ECM组分来制造组织工程血管移植物（TEVG）提供了新的见解。
The regeneration of smooth muscle with physiological functions has been a key challenge in vascular tissue engineering. Hyaluronan (HA), as a major component of the extracellular matrix, plays a vital role in regulating tissue injury and repair. In this study, a biomimetic vascular graft was prepared by co-electrospinning of synthetic degradable polymers and native ECM components including collagen type-I as well as low and high molecular weight HA (LMW HA and HMW HA). Upon implantation in the rat abdominal aorta, the grafts exhibited sustained HA release that effectively enhanced the regeneration of vascular smooth muscle. Besides, LMW HA loaded vascular grafts demonstrated rapid endothelialization compared to the other groups. More importantly, HA-loaded poly(L-lactide-co-caprolactone) grafts demonstrated an optimal vascular media layer accompanied by well-organized elastin fibers after long-term implantation (6 months), and they maintained potent physiological function up to 1/3 that of the native artery. In contrast, inadequate smooth muscle regeneration was observed in poly(epsilon-caprolactone) grafts due to slow degradation restricting the regeneration. The mechanism was further investigated and explained by the HA-induced migration of smooth muscle cell (SMC) via CD44-mediated signaling. Besides, low molecular weight HA can promote the migration of vascular progenitor cells that further differentiate into SMCs. These results highlight the importance of HA in the regeneration of functional vascular smooth muscle, and provide a new insight into the fabrication of tissue engineering vascular grafts (TEVGs) via combining rapidly degradable polymers and bioactive ECM components that hold great translational potential.