Implementation of a fully biodegradable and biomimetic epicardial patch providing synergic physico-chemical, mechanical and electrical cues for myocardial infarction therapy

The intrinsic limitation of myocardial tissue to self-repair after damage underscores the need for innovative approaches in addressing cardiac tissue damage post-myocardial infarction (MI). We aimed to develop an acellular, bioartificial, microstructured and electroconductive patch (PGF) made of poly(lactic-co-glycolic acid) (PLGA), Gelatin, and 9-fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF), to foster post-MI endogenous cardiac healing capabilities. The self-assembling semi-conductive peptide Fmoc-FF was introduced to reduce the electrical impedance of the polymer components while maintaining the complete biodegradation of the patch. Unexpectedly, the electroconductive component was found to increase the patch microstructure stability, improve cardiomyoblast elongation, augment stromal cell differentiation and sustain Human induced Pluripotent Stem Cell-derived Cardiomyocytes (hiPSC-CM) beating for at least 30 days. The main outcome was demonstrated in vivo, where epicardial implantation of the PGF patch in a rat model of ischaemia-reperfusion promoted significant cardiac tissue repair: this was evidenced by preservation of the myocardial tissue, reduced fibrosis, and recruitment of endogenous c-Kit+ cells. This newly implemented patch configuration promotes efficient myocardial healing, offering a promising therapeutic approach for infarcted patients.