Topological butterfly wings for human induced pluripotent stem cell-derived cardiomyocyte maturation and myocardial infarction treatment

Abstract

Myocardial infarction (MI) causes irreversible myocardial cell loss; however, current treatments are limited to slowing disease progression rather than restoring lost myocardium. Cardiac tissue engineering, based on inexhaustible human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), becomes an ideal treatment method for supplying exogenous cardiomyocytes (CMs) to help contractile function recovery. However, hiPSC-CMs currently used are usually immature, which might trigger ventricular arrhythmias in MI treatments and limit their application in myocardial tissue engineering. The topological structure, as one of the most effective cues in controlling cellular functions, may benefit hiPSC-CM maturation. Here, the natural topological Morpho Menelaus butterfly wings (BFW) were chosen to regulate hiPSC-CM maturation and form the grafts for MI treatment. Immunofluorescence and calcium imaging tests confirmed that the parallel nanoridges on the surface of BFW oriented cellular growth and enhanced gap junction formation and improved the calcium handling ability of hiPSC-CMs, which demonstrated the maturation of hiPSC-CMs. BFW-matured hiPSC-CMs were transplanted as a patch for MI treatment evaluation, and twenty-eight days after engraftment, the histological destruction and contractile function of MI mice were improved obviously. This work provides an effective method for promoting hiPSC-CM maturation and potentially expands the application of natural materials in myocardial tissue engineering.