Mechano-matching hydrogel patch promotes myocardial infarction repair via YAP-Bcl-2 pathway activation

), mitigating myocardial fibrosis, and attenuating cardiomyocyte apoptosis. To dissect the underlying mechanism, an in vitro cyclic stretch model mimicking the in vivo myocardial mechanical microenvironment was established. Results revealed that hydrogels with moderate stiffness (16.82 kPa) transduced mechanical cues to promote nuclear translocation of Yes-associated protein (YAP) in cardiomyocytes. This key mechanotransduction event upregulated the expression of anti-apoptotic protein Bcl-2, thereby suppressing cardiomyocyte apoptosis. Notably, this study uncovers a previously unelucidated mechanistic paradigm by which moderate mechanical stimuli, matching the intrinsic stiffness of native myocardium, confer cardioprotection specifically through activation of the YAP-Bcl-2 signaling axis. Furthermore, it establishes that acellular biomaterials can exclusively harness their intrinsic mechanical properties to reverse pathological myocardial remodeling post-MI, without relying on cellular components or bioactive molecules. This finding provides strategy guided by mechanobiology for cardiac regeneration, substantially enhancing the clinical translatability of acellular cardiac patches.