Topic: Extracellular Vesicles and Circulating Nucleic Acids in Musculoskeletal Diseases: From Molecular Mechanisms to Biomarkers and Translational Therapeutics

Musculoskeletal diseases, including osteoarthritis, osteoporosis, osteonecrosis, fracture nonunion, bone defects, tendon and ligament injuries, intervertebral disc degeneration, inflammatory joint diseases, and implant-associated complications, impose a major global health burden. Emerging evidence identifies extracellular vesicles (EVs) as key mediators of intercellular communication in musculoskeletal tissues. Through the transfer of proteins, lipids, metabolites, and nucleic acids, EVs regulate bone remodeling, cartilage degeneration, synovial inflammation, osteoimmunology, angiogenesis, senescence, immune responses, and tissue repair.

At the same time, EV-associated circulating nucleic acids are attracting growing interest as minimally invasive biomarkers. EV-derived miRNAs, lncRNAs, circRNAs, cfDNA, and mtDNA in blood, synovial fluid, bone marrow, urine, and other biofluids may support diagnosis, prognosis, patient stratification, disease monitoring, and treatment evaluation. In parallel, native and engineered EVs, EV-mimetic nanovesicles, and biomaterial-assisted delivery systems are expanding therapeutic opportunities in treating injuries and chronic diseases of bone, cartilage, tendon and ligament, intervertebral disc, and associated nerves, as well as in promoting tissue-implant integration.

This Special Issue welcomes original research and reviews addressing the roles of EVs in musculoskeletal biology, as well as their applications in biomarker discovery, liquid biopsy, regenerative therapeutics, and translation for musculoskeletal diseases.

● EV biogenesis, cargo sorting, and intercellular communication in musculoskeletal homeostasis, remodeling, and disease progression;

● EV-mediated mechanisms in musculoskeletal diseases, such as osteoarthritis, osteoporosis, osteonecrosis, fracture nonunion, bone defects, inflammatory joint diseases, intervertebral disc degeneration, tendon and ligament injuries, and implant-associated complications;

● EVs in osteoimmunology, synovial inflammation, angiogenesis, senescence, immune regulation, and tissue microenvironment remodeling;

● EV-associated circulating nucleic acids, liquid biopsy, multi-omics, single-vesicle analysis, and artificial intelligence-assisted approaches for biomarker discovery, diagnosis, prognosis, patient stratification, and disease monitoring;

● Native and engineered EVs, EV-mimetic nanovesicles, targeted EVs, and biomaterial-assisted delivery systems for musculoskeletal regeneration, repair, and translational therapeutics.

extracellular vesicles, circulating nucleic acids, musculoskeletal diseases, osteoarthritis, osteoporosis, liquid biopsy, EV biomarkers, engineered extracellular vesicles, regenerative therapeutics, osteoimmunology