Theranostics 2018; 8(18):5159-5177. doi:10.7150/thno.27760
Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization
Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Anatomy, Southern Medical University, Guangdong, Guangzhou 510515, China.
# These authors contributed equally to this work.
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
He Y, Ye G, Song C, Li C, Xiong W, Yu L, Qiu X, Wang L. Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization. Theranostics 2018; 8(18):5159-5177. doi:10.7150/thno.27760. Available from http://www.thno.org/v08p5159.htm