Mussel-inspired conductive nanofibrous membranes repair myocardial infarction by enhancing cardiac function and revascularization

Abstract

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.

Nanoengineering in Cardiac Regeneration: Looking Back and Going Forward

“…Moreover, the implant of this dual growth factor-loaded patch in a rabbit having undergone AMI evidenced blood vessel sprouting in the patch secured region with consequent improvement of functional regeneration of cardiac tissue [106]. He et al confirmed that neovascularization was accompanied by a reduction in infarct size extension as well as cardiac function improvement in an in vivo study [107].…”

Current advances in biodegradable synthetic polymer based cardiac patches

“…Phase separation and salt leaching fabrication methods can process them into porous scaffolds (Figure 2f–g; (Hashizume, Fujimoto, et al, ; Ravichandran et al, ). Electrospinning is a common way to fabricate nano or sub‐micro fibrous scaffolds (Figure 2h; He et al, ), while phase separation can also achieve nano‐fibrous morphology (Figure 2i; Liu et al, ). Additionally, patches with pattern surface were fabricated using film casting (Figure 2j; Cristallini et al, ).…”

“…Copyright 2013, published by Elsevier Ltd. (h) Electrospun GelMA/PCL. Reproduced with permission (He et al, ). Copyright 2018, published by Theranostics.…”

Silk‐Based Biomaterials for Cardiac Tissue Engineering

“…[5] Conductive materials such as graphene oxide, PPy, and carbon nanotubes (CNTs) are common raw materials used for conductive scaffolds fabrication. [54][55][56] Third, once therapeutic cells are transplanted into the infarcted region, scaffolds should help retain cells, which require materials to provide plenty of cell adhesion sites. In addition, the degradation rate of the scaffold material needs to match the rate of the production of ECM.…”