An Engineered Hierarchical Hydrogel with Immune Responsiveness and Targeted Mitochondrial Transfer to Augmented Bone Regeneration

Abstract Coordinating the immune response and bioenergy metabolism in bone defect environments is essential for promoting bone regeneration. Mitochondria are important organelles that control internal balance and metabolism. Repairing dysfunctional mitochondria has been proposed as a therapeutic approach for disease intervention. Here, an engineered hierarchical hydrogel with immune responsiveness can adapt to the bone regeneration environment and mediate the targeted mitochondria transfer between cells. The continuous supply of mitochondria by macrophages can restore the mitochondrial bioenergy of bone marrow mesenchymal stem cells (BMSC). Fundamentally solving the problem of insufficient energy support of BMSCs caused by local inflammation during bone repair and regeneration. This discovery provides a new therapeutic strategy for promoting bone regeneration and repair, which has research value and practical application prospects in the treatment of various diseases caused by mitochondrial dysfunction.