A biomimetic PLLA/MXene piezoelectric hydrogel promotes jawbone regeneration via mitochondrial autophagy-dependent Immunometabolic reprogramming

To address the issue of lacking tissue specificity in existing piezoelectric materials for bone repair, this study developed for the first time a biomimetic PLLA/MXene piezoelectric conductive hydrogel based on the tissue-specific piezoelectric coefficient of jawbone (∼7.53 pC/N). By incorporating MXene and applying polarization treatment, the piezoelectric performance of the hydrogel was precisely matched to that of natural jawbone, while its electrical conductivity was significantly enhanced. Under ultrasound stimulation, the hydrogel generates localized electrical signals, effectively driving macrophage polarization toward the pro-healing M2 phenotype. This remodeling of the immune microenvironment further synergistically enhances the osteogenic differentiation of bone marrow mesenchymal stem cells and the angiogenic activity of human umbilical vein endothelial cells. Animal experiments confirmed that the hydrogel significantly promotes bone regeneration and collagen mineralization in rat jawbone defect areas. Mechanistically, its immunomodulatory function stems from regulating macrophage polarization by enhancing mitophagy and oxidative phosphorylation. This study provides a novel and tissue-specific intelligent biomaterial strategy for precise jawbone defect repair.