Melt electrowritten Medium Chain Length Polyhydroxyalkanoate Cardiac Patches for Post-MI Cardiac Regeneration

Abstract Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold promise in averting functional decline towards heart failure following myocardial infarction (MI). However, challenges persist in retaining these cells within the myocardium. We developed a novel three-dimensional cardiac patch and evaluated its potential to prevent post-MI functional decline. For the first time, melt electrowritten (MEW), structurally anisotropic scaffolds were derived from high molecular weight, medium chain-length polyhydroxyalkanoates (MCL-PHAs). These scaffolds supported hPSC-CMs, facilitating their rapid structural and functional maturation in vitro. Different cellular combinations were seeded on the scaffolds and layered to create cardiac patches. These were well-accepted in a murine MI model, without capsule formation. Patches containing hPSC-derived cardiac microvascular-like endothelial cells initiated vascular regeneration; although, this did not prevent post-MI functional decline. This novel advancement enabled the production of MCL-PHA-based MEW-cardiac patches that matured hPSC-CMs and promoted vascular regeneration, offering potential for future improvement in cardiac function through enhanced hPSC-CM retention.