Mitochondria-mimetic nanomedicine restores mitochondrial homeostasis to rescue traumatic and osteoporotic bone loss

Abstract Trauma-induced bone defects and age-related osteoporosis are prevalent osteogenic disorders in which impaired osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) remains a critical pathological challenge. Typically, BMSCs facilitate osteogenesis and increase bone mass by differentiating into osteoblasts; however, this differentiation is a high-energy process. In aging or trauma, BMSCs within the bone marrow exhibit substantial mitochondrial dysfunction, which severely limits their osteogenic potential and subsequent bone replenishment. Therefore, we developed a targeted biomimetic strategy to isolate mitochondria derived from BMSCs and formulated a membrane coating on poly(lactic-co-glycolic acid) nanoparticle cores, which were loaded with coenzyme Q10 (CoQ10) to facilitate mitochondrial repair. This engineered construct, M-NPs@CoQ10, demonstrates significantly enhanced cellular internalization and mitochondrial targeting. It exhibits superior efficacy in restoring mitochondrial function and promoting osteogenic differentiation both in vitro and in vivo. In murine models of trauma-mediated bone defects and age-induced osteoporosis, M-NPs@CoQ10 treatment achieved robust bone-recovery rates of 80% and 75%, respectively. This approach is a novel and highly effective therapeutic strategy for metabolic bone repair and related skeletal diseases.