Exosomes in Orthopedic Regeneration: A Global Bibliometric Review (2001–2025)

Background Extracellular vesicles (EVs), and exosomes in particular, are being developed as cell-free therapeutics for musculoskeletal repair. The structure of this research field, and its distance from clinical application, have not been quantified across the full range of orthopedic tissues. Objectives To map the global research landscape of exosome and EV research in orthopedic regeneration, to position it against previously published bibliometric analyses, and to quantify where research attention diverges from the requirements of clinical translation. Methods This bibliometric review was reported in accordance with the BIBLIO guideline. The Web of Science Core Collection (Science Citation Index Expanded) was searched on November 10, 2025, for Articles and Reviews published from January 1, 2001. The de-duplicated export of 3,728 records was analyzed with VOSviewer 1.6.19, CiteSpace 6.4.R1, and documented scripts that are deposited with the derived data. Ten records carrying a 2026 cover year were retained in the network analyses and excluded from all annual time series (n = 3,718). Translational readiness was assessed by counting, per year, records whose title, abstract, or keywords matched fixed regular expressions for delivery engineering, additive manufacturing, engineered EVs, clinical evaluation, and manufacturing or potency control. Results Annual output rose from 39 records in 2015 to 634 in 2025 (log-linear growth 2015–2025, 32.3% per year, 95% CI 24.1–41.1%, R² = 0.92), with deceleration from 54.5% per year in 2015–2020 to 13.1% in 2020–2025. China contributed 2,146 records (57.6%) and the United States 532 (14.3%), together 71.8% of the corpus; the United States had higher citation density (56.8 versus 33.9 citations per record) and the highest co-authorship total link strength (393 versus 282). Records with authors from more than one country accounted for 18.5%. All ten most productive institutions were Chinese, led by Shanghai Jiao Tong University (n = 212). Keyword co-occurrence clustering in CiteSpace resolved 12 clusters (modularity Q = 0.442, mean silhouette S = 0.71) spanning regenerative applications, disease-specific themes, and cell-biological foundations. Of 65 keyword citation bursts, five remained active at the search date, the strongest being “hydrogel” (strength 5.19, 2023–2025). Records addressing hydrogel delivery increased from 15 (2020) to 140 (2025) and engineered EVs or EV mimetics from 8 to 48, whereas records mentioning good manufacturing practice, potency assays, scalable production, or batch-to-batch consistency totalled 27 across 2001–2025 (0.7%) and did not increase. Conclusions Orthopedic exosome research has shifted from EV cell biology toward delivery engineering, is geographically concentrated, and is almost entirely preclinical. The bibliometric evidence indicates that the literature addressing standardized manufacturing, potency definition, and clinical evidence generation remains quantitatively marginal relative to the literature on delivery. This review maps published attention; it does not evaluate the efficacy or safety of any EV-based intervention.