Injectable Thermosensitive Hydrogel-Loaded Exosomes Promote Diabetic Periodontal Bone Regeneration

This study aimed to explore the key role of mesenchymal stem cell exosomes in stabilizing endothelial cell mitochondrial homeostasis, thereby establishing a direct link between endothelial cell mitochondrial homeostasis and the regulation of vascularized bone regeneration, and providing new insights into strategies for promoting bone regeneration in the diabetic environment. In this study, cell biology, molecular biology and biochemistry techniques, laboratory animal techniques and bioinformatics analysis were used to verify the therapeutic effect of BMSCs exosomes on endothelial cells under high glucose environment, and initially explore the mitochondrial function. Secondly, the physicochemical properties of injectable hydrogels were tested. Finally, it was applied to the alveolar bone defect model of diabetic rats, and the target protein of mitochondria was further explored by bioinformatics analysis. Our in vitro findings demonstrate that exosomes effectively regulate mitochondrial homeostasis and significantly improve endothelial cell function in a hyperglycemic niche. To optimize their therapeutic potential, exosomes are loaded in an injectable thermosensitive hydrogel for in vivo applications. Results show that the hydrogel-delivered exosomes significantly enhance angiogenesis and vascularized bone regeneration in a diabetic periodontal bone defect model. Further mechanistic studies reveal that exosomes promote mitochondrial fusion by upregulating the expression of optic atrophy protein Opa1, thereby restoring mitochondrial function in endothelial cells. These findings identify a promising target for periodontal bone regeneration therapies and offer new perspectives for advanced biomaterial design in regenerative medicine.