A Strongly Robust Chitosan‐Based Programmed Control Functional Hydrogel Improved Mitochondrial Function and Pro‐Vascularization for Adaptive Repair of Myocardial Infarction

Abstract Hydrogel‐based engineered cardiac patches (ECP) hold great promise as potential treatment options for myocardial infarction (MI). However, optimizing the preparation of ECP with better biocompatibility, mechanical stability, and adaptation to MI repair remains a challenge. In this study, a chitosan (CS) hydrogel with good mechanical robustness through programmed control of hydrogen bonding is constructed to adapt to the continuous beating of myocardial tissue. With the synergistic effects of lipoic acid (TA), proanthocyanidins (PAs), and Eu 3+ , a functional platform capable of improving mitochondrial function, antioxidation, and pro‐vascularization is further constructed for the adaptive repair of the MI microenvironment. The fabricated functionalized chitosan hydrogel (CS/TA@PAs‐Eu) possessed good mechanical stability and ionic conductivity, showing the potential for long‐term adaptation to myocardial tissue pulsation. Also, the CS/TA@PAs‐Eu hydrogel promoted cardiomyocytes (CMs) maturation and functionalization, and effectively improved mitochondrial function, scavenged reactive oxygen species (ROS) as well as promoted angiogenesis. Animal studies indicated that the CS/TA@PAs‐Eu hydrogel can perform adaptive repair of MI to prevent left ventricular (LV) remodeling and restore cardiac function. This study highlights a functionalized hydrogel ECP with good biocompatibility and mechanical robustness for the adaptive repair of MI.