Exosomes for Ligament and Tendon Regenerative Therapies: A Narrative Review

Background and/or Objectives: To synthesize in narrative review format, current preclinical data on exosome-based regenerative strategies for tendons and ligaments, highlighting key gaps in clinical translation and proposing future research directions to optimize therapeutic efficacy and delivery.

Design: Narrative Review

Setting : not applicable

Participants : not applicable

Interventions: not applicable

Main Outcome Measures: not applicable

Results: Limited preclinical studies suggest that exosomes derived from mesenchymal stem cells, tendon stem/progenitor cells, and dental-derived stem cells may offer an alternative approach for tendon and ligament repair, circumventing challenges associated with direct stem cell transplantation. Exosomes from these cells have shown to facilitate healing by modulating inflammation, promoting collagen synthesis, and enhancing extracellular matrix remodeling. Their effects are largely mediated through miRNA cargo regulation, macrophage polarization, and key signaling pathways (AKT/mTOR, SMAD, NF-κB inhibition). Furthermore, exosome-loaded scaffolds and smart cellular constructs have emerged as promising strategies to enhance regenerative outcomes by improving targeted delivery.

Conclusions: Exosome therapy has promising, although limited, preclinical data and early clinical trials should be performed to confirm efficacy as some providers are already utilizing exosomes as a novel regenerative therapy.