Therapeutic strategy for exosome-based bone regeneration to osteoporosis: Challenges and potential solutions

Exosomes derived from mesenchymal stem cells, osteoblasts, osteoclasts, and macrophages regulate bone homeostasis by modulating osteogenesis, osteoclastogenesis, and immune responses. Their regenerative effects in non-osteoporotic settings are well documented. However, challenges such as exosome heterogeneity, rapid clearance, and poor targeting efficiency impede their direct application in osteoporosis. Recent bioengineering approaches, including osteogenic RNA or protein loading and surface modifications for bone targeting, show promise. Moreover, combining exosomes with immunomodulatory or synergistic therapies may further enhance their efficacy. Despite these advances, gaps persist in standardizing isolation techniques, ensuring batch consistency, and scaling up production for clinical use. This review consolidates current knowledge and outlines directions for adapting exosome-based bone regenerative strategies to osteoporosis treatment.