Biomaterial design strategies for enhancing mitochondrial transplantation therapy

Mitochondrial dysfunction is linked to various diseases, such as ischemic syndrome and type 2 diabetes, primarily due to insufficient energy supply caused by low adenosine triphosphate levels. Mitochondrial transplantation therapy is an emerging therapeutic strategy that can supplement the respiratory capacity of damaged mitochondria, thereby addressing mitochondrial disorders at their root. However, poor viability after isolation from cells, difficulties in targeting delivery in vivo, and low cellular internalization efficiency constitute the major challenges for the clinical translation of mitochondrial transplantation. The integration of advanced biomaterial design may hold the key to address these issues and improve the therapeutic efficacy of mitochondrial transplantation. In this review, we summarize recent advancements in biomaterial-assisted mitochondrial transplantation by protecting mitochondria during delivery, improving the targeting efficiency in vivo, and facilitating mitochondrial internalization. We also emphasize the importance of synergistic therapy of mitochondrial transplantation with other therapies. Finally, we discuss current issues and potential future directions of biomaterial-assisted mitochondrial transplantation therapy, aiming to further promote its clinical translation.