Extracellular vesicle-loaded hydrogels for diabetic bone healing

The bone healing cascade is initiated by an inflammatory response, which in turn mediates regenerative repair and culminates in the restoration of bone tissue. An imbalanced immune response during the early stage of bone regeneration disrupts the healing cascade, delaying bone healing and compromising therapeutic outcomes. Diabetes induces oxidative stress and inflammation, disturbs bone metabolism, increases the risk of infection, decreases bone scaffold efficacy, and hinders bone defect repair. Interest in the use of smart hydrogels with precise stimulus responsiveness in bone repair and regeneration has increased. Integrated responsive groups or nanoparticles enable them to regulate the local microenvironment and facilitate bone regeneration. However, challenges remain due to fragility and poor tissue adhesion of hydrogels. Extracellular vesicles (EVs) serve as promising cell-free candidates for bone repair, yet direct injection leads to fast capture and elimination, curbing therapeutic outcomes. Hydrogel carriers modified with EVs are adopted to increase vesicle retention and repair performance. This paper summarizes the updated progress in the use of vesicle-loaded scaffolds for bone regeneration, covering vesicle origins and biomaterial combination tactics. It further clarifies relevant repair mechanisms, analyzes clinical translation hurdles, and proposes optimization directions for high-efficiency vesicles. These findings offer reference data for the design of advanced vesicle-based implants to facilitate bone recovery under diabetic conditions.