Engineered exosome biomedical technologies for precision diagnosis and therapy in orthopedic diseases

With population aging and sports-related injuries on the rise, the incidence of osteoarthritis, osteoporotic fractures, nonunion bone defects, and bone tumors continues to increase, while conventional pharmacologic and surgical interventions face limitations in target specificity, safety, and cost-effectiveness. Extracellular vesicles, particularly exosomes, are cell-derived nanoscale vesicles that can be engineered via surface ligand/peptide conjugation, membrane protein engineering, and nucleic acid or protein cargo loading to improve targeting, stability, and controlled release. These advances position engineered exosomes as promising platforms for the diagnosis and treatment of orthopedic disorders. Here, we review exosome architecture and biological properties, and systematically summarize extraction, purification, and engineering strategies, alongside their applications to osteoarthritis, osteoporosis, fracture healing, and bone malignancies. Reported therapeutic mechanisms include promotion of osteogenesis and angiogenesis, immunomodulation and anti-inflammatory effects, and regulation of autophagy and apoptosis. Nevertheless, significant barriers remain for clinical translation. To enable routine clinical use, future work should address product heterogeneity, scalable manufacturing, cargo stability, release kinetics, and long-term safety, supported by robust quality control and standardization. Finally, we adopt a technology-centric framework that maps engineering modalities to orthopedic indications and quantifiable performance metrics, outlining the review's methodological route and evidence synthesis approach.