Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Anatomy, Southern Medical University, Guangdong, Guangzhou 510515, China.
Theranostics. 2018 Oct 6;8(18):5159-5177. doi: 10.7150/thno.27760. eCollection 2018.
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. 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 and . 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 . 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. 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.
聚吡咯（Ppy）的生物相容性与其在纳米纤维上的聚集之间的争议阻碍了将导电 Ppy 掺入纳米纤维应用于创建工程心脏微环境。本研究的目的是使用高浓度的甲基丙烯酰酐-明胶（GelMA）-Ppy 纳米颗粒、贻贝启发的交联剂和静电纺丝（ES）-GelMA/聚己内酯（PCL）纳米纤维膜制造用于工程心脏贴片（ECP）的功能性支架。首先，当 GelMA 的甲基丙烯酰基通过 Ppy 的氧化聚合形成自交联网络时，获得了球形 GelMA-Ppy 纳米颗粒。其次，贻贝启发的多巴胺-N'N'-亚甲基双丙烯酰胺（多巴胺-MBA）交联剂使 GelMA-Ppy 纳米颗粒均匀交联在 ES-GelMA/PCL 膜上。最后，研究了基于多巴胺的导电功能 ECP 支架的可行性。GelMA-Ppy 纳米颗粒在 50mg/mL 的高浓度下表现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 纳米颗粒产生了基于多巴胺的（基于多巴的）导电膜的高导电性，增强了心肌细胞（CMs）的功能，并产生了它们的同步收缩。GelMA-Ppy 纳米颗粒还可以修饰原始 ES-GelMA/PCL 膜的形貌，以促进血管生成。将导电膜衍生的 ECP 移植到梗塞心脏 4 周后，梗塞面积减少了约 50%，左心室缩短分数百分比（LVFS%）增加了约 20%，梗塞区域的新生血管密度增加了约 9 倍与 MI 组相比。我们的研究报告了一种简便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 可以通过增强心脏功能和血管生成来修复梗塞心肌。
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