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Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization
Theranostics ( IF 12.4 ) Pub Date : 2018-10-06 , DOI: 10.7150/thno.27760
Yutong He , Genlan Ye , Chen Song , Chuangkun Li , Weirong Xiong , Lei Yu , Xiaozhong Qiu , Leyu Wang

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.

Keywords: dopamine, polypyrrole nanoparticles, electrospun membrane, myocardial infarction, revascularization



中文翻译:

贻贝启发的导电纳米纤维膜通过增强心脏功能和血运重建来修复心肌梗塞

聚吡咯(Ppy)的生物相容性及其在纳米纤维上的聚集之间的争论阻碍了掺入导电Ppy的纳米纤维的应用,以创建工程化的心脏微环境。这项研究的目的是使用高浓度的甲基丙烯酸酐-明胶(GelMA)-Ppy纳米粒子,贻贝启发的交联剂和电纺(ES)-GelMA /聚己内酯( PCL)纳米纤维膜。

方法:首先,当PelMA的甲基丙烯酸酯基通过Ppy氧化聚合形成自交联网络时,获得球形GelMA-Ppy纳米颗粒。其次,通过贻贝启发的多巴胺-N'N'-亚甲基-双丙烯酰胺(多巴胺-MBA)交联剂,在ES-GelMA / PCL膜上均匀交联GelMA-Ppy纳米颗粒。最后,在体外体内研究基于多巴的导电功能性ECP支架的可行性。

结果: GelMA-Ppy纳米颗粒在50 mg / mL的高浓度下显示出优异的生物相容性。大量的GelMA-Ppy纳米颗粒可以通过多巴胺-MBA交联剂均匀分布在ES纳米纤维上,而没有明显的聚集。高浓度的GelMA-Ppy纳米颗粒可产生多巴胺基(多巴基)导电膜的高电导率,从而增强心肌细胞(CMs)的功能并产生同步收缩。GelMA-Ppy纳米颗粒还可以改变原始ES-GelMA / PCL膜的形貌,以促进体外血管生成。将导电膜衍生的ECP移植到梗塞的心脏上4周后,梗塞面积减少了约50%,左心室缩短百分比(LVFS%)增加了约20%,并且与梗塞组相比,梗塞面积显着增加了约9倍。

结论:我们的研究报告了一种简便有效的方法,该方法基于贻贝启发性的导电纳米纤维膜开发功能性ECP。这种功能性ECP可以通过增强心脏功能和血运重建来修复梗塞心肌。

关键词:多巴胺,聚吡咯纳米颗粒,电纺膜,心肌梗死,血运重建

更新日期:2018-10-08
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