Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization.
Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization.
复制标题
作者：
He Y;Ye G;Song C;Li C;Xiong W;Yu L;Qiu X;Wang L
聚吡咯的生物相容性和聚吡咯在纳米纤维上的聚集性之间的争论阻碍了导电聚吡咯纳米纤维在创造工程化心脏微环境方面的应用。本研究的目的是利用高浓度甲基丙烯酸酐-明胶(GelMA)-Ppy纳米颗粒、贻贝类交联剂和电纺(ES)-GelMA/聚己内酯(PCL)纳米纤维膜，构建一种用于工程心脏补片(ECP)的功能支架。方法：首先，通过氧化聚合，使GelMA的甲基丙烯酸酯基团形成自交联网络，得到球形的GelMA-Ppy纳米粒子。其次，通过贻贝诱导的多巴胺-N‘N’-亚甲基双丙烯酰胺(DA-MBA)交联剂，在ES-GelMA/PCL膜上实现了GelMA-Ppy纳米粒子的均匀交联。最后，对多巴基导电功能性ECP支架的体内外可行性进行了研究。结果：GelMA-Ppy纳米粒在50 mg/mL浓度下具有良好的生物相容性。大量的GelMA-Ppy纳米粒子可以通过多巴胺-MBA交联剂均匀分布在ES纳米纤维上，没有明显的团聚现象。高浓度的GelMA-Ppy纳米粒子使基于多巴胺的导电膜具有较高的电导率，从而增强了心肌细胞的功能并使其产生同步收缩。GelMA-Ppy纳米粒子还可以修饰原始ES-GelMA/PCL膜的形貌，促进体外血管形成。与MI组比较，心肌梗死组心肌梗死面积缩小约50%，左心室短轴缩短率(LVFS%)增加约20%，梗死区新生血管密度增加约9倍。结论：我们的研究报告了一种简便而有效的方法来开发基于贻贝启发的导电纳米纤维膜的功能性ECP。这种功能性ECP可以通过增强心功能和血管重建来修复梗死心肌。
The controversy between polypyrrole's (Ppy) biocompatibility and its aggregation on nanofibers impedes application of conductive Ppy-incorporated nanofibers to create engineered cardiac microenvironments. The purpose of this study was to fabricate a functional scaffold for engineering cardiac patches (ECP) using a high concentration of methyl acrylic anhydride-gelatin (GelMA)-Ppy nanoparticles, mussel-inspired crosslinker, and electrospun (ES)-GelMA/polycaprolactone (PCL) nanofibrous membrane. Methods: First, spherical GelMA-Ppy nanoparticles were obtained when the methacrylate groups of GelMA formed a self-crosslinked network through oxidative polymerization of Ppy. Second, GelMA-Ppy nanoparticles were uniformly crosslinked on the ES-GelMA/PCL membrane through mussel-inspired dopamine-N'N'-methylene-bis-acrylamide (dopamine-MBA) crosslinker. Finally, the feasibility of the dopa-based conductive functional ECP scaffold was investigated in vitro and in vivo. Results: The GelMA-Ppy nanoparticles displayed excellent biocompatibility at a high concentration of 50 mg/mL. The massive GelMA-Ppy nanoparticles could be uniformly distributed on the ES nanofibers through dopamine-MBA crosslinker without obvious aggregation. The high concentration of GelMA-Ppy nanoparticles produced high conductivity of the dopamine-based (dopa-based) conductive membrane, which enhanced the function of cardiomyocytes (CMs) and yielded their synchronous contraction. GelMA-Ppy nanoparticles could also modify the topography of the pristine ES-GelMA/PCL membrane to promote vascularization in vitro. Following transplantation of the conductive membrane-derived ECP on the infarcted heart for 4 weeks, the infarct area was decreased by about 50%, the left ventricular shortening fraction percent (LVFS%) was increased by about 20%, and the neovascular density in the infarct area was significantly increased by about 9 times compared with that in the MI group. Conclusion: Our study reported a facile and effective approach to developing a functional ECP that was based on a mussel-inspired conductive nanofibrous membrane. This functional ECP could repair infarct myocardium through enhancing cardiac function and revascularization.