Coaxially Electrospun Myocardial dECM‐ Based Nanofibrous Scaffolds Demonstrate Enhanced Cardiomyocyte Biocompatibility

The limited regenerative capability of mature cardiomyocytes (CMs) makes myocardial repair more challenging, requiring effective and viable alternatives to conventional heart transplants. Cardiac tissue engineering is a substitutionary approach combining cells, scaffolds, and growth factors to develop functional heart tissues in vitro. Induced pluripotent stem cells (iPSCs) represent a significant advancement in cardiac regenerative medicine, offering a continuous supply of CMs, however, the limited understanding of their microenvironment hinders translational research. Decellularized extracellular matrix (dECM) derived from myocardium is a highly promising natural scaffold for CTE, given its tissue-specific composition, mechanical properties, and biochemical cues that promote cellular regeneration. This study investigates myocardial dECM-based fibrous scaffolds for iPSC-derived CM use. Coaxially electrospun nanofibers comprising a polyurethane core and a blend of polycaprolactone and myocardial dECM as the sheath were optimized. Morphological analysis confirms the resemblance of the nanofibers to fibrillar collagen in the native dECM. ATR- FTIR and immunostaining results confirm the presence of dECM, which enhanced their hydrophilicity and enzymatic degradation. Biocompatibility results show higher phenotypic retention of iPSC-CMs due to microenvironments enriched with native proteins. On the contrary, the scaffolds without myocardial proteins exhibit higher dedifferentiation of iPSC-CMs, proving that ECM proteins provide a suitable microenvironment for iPSC-CMs.