Regulation of Mitochondrial Homeostasis: Applications of Nanobiomaterials in Age-Related Bone Diseases

Age-related bone diseases are a heterogeneous group of metabolic disorders characterized by progressive degenerative changes. Although nanobiomaterials have emerged as a promising means of regulation at the cellular level, their therapeutic efficacy remains very limited due to the lack of treatment strategies that directly target mitochondrial pathology. In recent years, nanobiomaterial therapies centered on mitochondria have attracted widespread attention. This review aims to critically evaluate the latest advances in this emerging field and categorize them into four main strategies: enhancing mitochondrial autophagy, optimizing the mitochondrial microenvironment, repairing mitochondrial structure, and implementing mitochondrial transfer therapy. Based on existing research, we have preliminarily established a multi-level intervention framework ranging from the clearance of dysfunctional mitochondria to the regulation of the microenvironment, and from the repair of structural components to the transplantation of healthy mitochondria, which has demonstrated encouraging proof-of-concept results in vitro and in animal models. However, this field remains in the preclinical exploration phase: the vast majority of studies are based on rodent models, the efficiency of mitochondrial-targeted delivery is generally low, and long-term biosafety and the feasibility of large-scale production have not yet been systematically evaluated. This review discusses the latest advances in mitochondrial-based nanobiomaterial therapies for age-related bone diseases. Furthermore, this review explores potential drugs and targets for the development of more effective nanobiomaterials, focusing on the key challenges facing the transition from the laboratory to clinical applications in this field, and is expected to provide novel insights into the future development of mitochondria-based nanobiomaterial therapies.