The Role of Exosomes in Bone Metastasis and Bone Tissue Engineering: Molecular Mechanisms and Therapeutic Opportunities

Exosomes, nanoscale extracellular vesicles secreted by almost all cell types, have emerged as pivotal mediators of intercellular communication within both pathological and regenerative microenvironments. In bone metastasis, tumor-derived exosomes (TDEs) play a crucial role in the establishment of pre-metastatic niches, modulation of osteoclast-osteoblast balance, and promotion of tumor cell colonization through the transfer of bioactive molecules such as proteins, lipids, and non-coding RNAs. Conversely, in bone tissue engineering, stem cell-derived exosomes have demonstrated remarkable potential to promote osteogenesis, angiogenesis, and tissue regeneration by activating signaling pathways that regulate bone remodeling. This dual role of exosomes-as drivers of disease progression and as therapeutic agents-highlights their significance as both diagnostic biomarkers and next-generation biologics. This review provides a comprehensive overview of the molecular mechanisms underlying exosome-mediated communication in bone metastasis and bone regeneration, summarizes recent advances in exosome-engineered biomaterials, and discusses the translational challenges that must be addressed to enable clinical applications. Understanding the multifaceted functions of exosomes will pave the way for the development of novel exosome-based strategies for the diagnosis and treatment of bone-related diseases.