Transplantation of mitochondria encapsulated in hydrogel ameliorates myocardial ischemia-reperfusion injury

Mitochondria play a central role in myocardial ischemia-reperfusion (I/R) injury. Therefore, mitochondrial transplantation (MTP) holds therapeutic potential for treating I/R injury. However, the transplantation environment (TE) could cause mitochondrial damage due to its high calcium concentration and physiological temperature, thus reducing MTP efficiency. Here, we use the hydrogel Pluronic F127 (PF127) to protect mitochondria during MTP to treat myocardial I/R injury. Our findings demonstrate that PF127 is compatible with mitochondria and forms a stable three-dimensional structure to encapsulate and protect them from the TE. PF127 significantly improves mitochondrial membrane potential (Delta psi m) and structural integrity. Additionally, PF127 enhances the internalization of transplanted mitochondria into cardiomyocytes. Our in vivo findings reveal that transplantation with PF127-encapsulated mitochondria improves cardiac function, reduces infarction size, and ameliorates adverse myocardial remodeling in mice after I/R injury. Likewise, our in vitro results indicate that this PF127-assisted MTP significantly improved the mechanic and metabolic capacities of cardiomyocytes after hypoxia-reoxygenation injury. These cardioprotective effects have been found to occur via the inhibition of apoptosis and oxidative stress. In conclusion, PF127 attenuates TE-induced mitochondrial dysfunction and enhances the therapeutic effects of MTP on myocardial I/R injury.