M2 macrophage-derived exosomes promote diabetic fracture healing by acting as an immunomodulator

Diabetes mellitus is a chronically inflamed disease that predisposes to delayed fracture healing. Macrophages play a key role in the process of fracture healing by undergoing polarization into either M1 or M2 subtypes, which respectively exhibit pro-inflammatory or anti-inflammatory functions. Therefore, modulation of macro-phage polarization to the M2 subtype is beneficial for fracture healing. Exosomes perform an important role in improving the osteoimmune microenvironment due to their extremely low immunogenicity and high bioactivity. In this study, we extracted the M2-exosomes and used them to intervene the bone repair in diabetic fractures. The results showed that M2-exosomes significantly modulate the osteoimmune microenvironment by decreasing the proportion of M1 macrophages, thereby accelerating diabetic fracture healing. We further confirmed that M2-exosomes induced the conversion of M1 macrophages into M2 macrophages by stimulating the PI3K/AKT pathway. Our study offers a fresh perspective and a potential therapeutic approach for M2-exosomes to improve diabetic fracture healing.

Automated summary

Diabetes mellitus predisposes to delayed fracture healing due to chronic inflammation. Macrophages polarization into M1 or M2 subtypes plays a crucial role in fracture healing with pro- or anti-inflammatory functions. M2-exosomes, with low immunogenicity and high bioactivity, were extracted in this study and used to intervene diabetic fracture healing. The results showed that M2-exosomes modulate the osteoimmune microenvironment by reducing M1 macrophages proportion, thus accelerating diabetic fracture healing. It was further confirmed that M2-exosomes induce M1 to M2 macrophage conversion through the PI3K/AKT pathway. This study provides a fresh perspective and potential therapeutic approach for M2-exosomes in improving diabetic fracture healing.