A Biocompatible Microdroplet Platform Incorporating MSC-Derived Exosomes for Bone Regeneration and Osteoporosis Treatment.

INTRODUCTION

Postmenopausal osteoporosis, characterized by progressive loss of bone mass and deterioration of skeletal microarchitecture, remains a major public health concern worldwide. Exosomes derived from mesenchymal stem cells (MSC-Exos) are nanosized extracellular vesicles enriched with bioactive cargo, have emerged as potent cell-free mediators of tissue regeneration and immunomodulation. However, their clinical translation is hindered by rapid clearance and insufficient retention at target sites. In this study, we developed a biocompatible microdroplet (MD)-based delivery platform incorporating MSC-derived exosomes (MD/Exos) and evaluated its therapeutic potential for osteoporosis treatment.

METHODS

MSC-Exos were isolated from human bone marrow-derived mesenchymal stem cells (hBMSCs) and characterized by transmission electron microscopy and exosomal marker analysis. MD/Exos were fabricated and evaluated for cellular uptake and cytocompatibility. The effects of MD/Exos on hBMSC proliferation, osteogenic differentiation, and macrophage inflammatory responses were investigated in vitro. Therapeutic efficacy was further assessed in an ovariectomy-induced osteoporotic rat model through histological and cytokine analyses.

RESULTS

MSC-Exos exhibited characteristic exosomal morphology and were efficiently internalized by both hBMSCs and RAW264.7 macrophages. The fabricated MD/Exos system demonstrated excellent cytocompatibility in vitro and favorable histocompatibility in vivo. In vitro, MD/Exos significantly enhanced osteogenic differentiation of hBMSCs and altered macrophage inflammatory cytokine profiles, suggesting a coordinated effect on osteogenesis and inflammatory regulation. In an ovariectomy-induced osteoporotic rat model, MD-Exo treatment effectively preserved trabecular bone microarchitecture, reduced marrow adiposity, and markedly inhibited osteoclast activity.

CONCLUSION

MD/Exos represent a promising exosome delivery strategy for osteoporosis treatment.