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

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，在体外和体内研究了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