Biomimetic Extracellular Vesicles Containing Biominerals for Targeted Osteoporosis Therapy

Osteoporosis (OP) is a systemic skeletal disorder characterized by decreased bone mineral density and a heightened risk of fractures. Therapies for OP have primarily focused on balancing bone formation and bone resorption, but enhancing the remineralization of osteoporotic bone is also a key strategy for effective repair. Recent insights into biomineralization mechanisms have highlighted the essential role of mineral-containing extracellular vesicles (EVs) secreted by osteoblasts in promoting bone marrow mesenchymal stromal/stem cell (BMSC) differentiation and initiating matrix mineralization. Drawing from these principles, we developed a biomimetic approach to replicate the structure and function of the osteoblast-derived EVs by engineering biomimetic mitochondrial minerals with bone marrow homing cell membranes (CMs). This bone-targeted biomimetic system exhibits excellent biocompatibility, enhancing osteogenic differentiation and stimulating angiogenesis by regulating cellular energy metabolism. Additionally, the CM-coated structure shows affinity for collagen fibrils, effectively enhancing intrafibrillar collagen mineralization, thereby facilitating osteoporotic bone repair. Overall, the biomimetic system offers a safe and efficient therapeutic alternative, positioning it as a platform for bone tissue engineering and regenerative medicine.