Engineering biomaterial-mediated delivery for osteoarthritis: targeting aging mechanisms to reestablish joint homeostasis

Biomaterials have emerged as versatile platforms for targeting aging-related pathways in osteoarthritis (OA), owing to their capacity for localized delivery, controlled release, microenvironmental regulation, and tissue repair. OA is a prevalent degenerative joint disease whose incidence continues to rise in aging populations, imposing substantial clinical and socioeconomic burdens. Rather than representing simple mechanical wear, OA is increasingly recognized as a disease closely associated with aging-related biological processes. Cellular senescence, mitochondrial dysfunction, impaired autophagy, and inflammaging disrupt cartilage homeostasis and accelerate joint degeneration. In this context, non-targeted therapies that mainly suppress pain or inflammation are unlikely to achieve durable disease modification, as they do not precisely intervene in the aging-associated drivers that sustain the OA microenvironment. Systemic anti-aging interventions may also be limited by insufficient joint accumulation, off-target effects, and potential adverse responses. Biomaterial-mediated targeting provides a rational strategy to enrich therapeutic cues in diseased joints, regulate aging-related pathways more precisely, and support long-term restoration of joint homeostasis. Platforms based on nanoparticles, natural polymers, and related biomaterials have shown potential to alleviate aging associated phenotypes, restore autophagy, suppress inflammation, and promote cartilage repair. These advances highlight biomaterials not only as delivery vehicles, but also as multifunctional platforms for mechanism driven OA intervention in the context of aging.