Intrinsic Tendon Regeneration After Application of Purified Exosome Product: An In Vivo Study

Elizabeth P. Wellings, Tony Chieh Ting Huang, Jialun Li, Timothy E. Peterson, Alexander W. Hooke, Andrew Rosenbaum, Chunfeng D. Zhao, Atta Behfar, Steven L. Moran, Matthew T. Houdek

Research output: Contribution to journalArticlepeer-review


Background: Tendons are primarily acellular, limiting their intrinsic regenerative capabilities. This limited regenerative potential contributes to delayed healing, rupture, and adhesion formation after tendon injury. Purpose: To determine if a tendon’s intrinsic regenerative potential could be improved after the application of a purified exosome product (PEP) when loaded onto a collagen scaffold. Study Design: Controlled laboratory study. Methods: An in vivo rabbit Achilles tendon model was used and consisted of 3 groups: (1) Achilles tenotomy with suture repair, (2) Achilles tenotomy with suture repair and collagen scaffold, and (3) Achilles tenotomy with suture repair and collagen scaffold loaded with PEP at 1 × 1012 exosomes/mL. Each group consisted of 15 rabbits for a total of 45 specimens. Mechanical and histologic analyses were performed at both 3 and 6 weeks. Results: The load to failure and ultimate tensile stress were found to be similar across all groups (P ≥.15). The tendon cross-sectional area was significantly smaller for tendons treated with PEP compared with the control groups at 6 weeks, which was primarily related to an absence of external adhesions (P =.04). Histologic analysis confirmed these findings, demonstrating significantly lower adhesion grade both macroscopically (P =.0006) and microscopically (P =.0062) when tendons were treated with PEP. Immunohistochemical staining showed a greater intensity for type 1 collagen for PEP-treated tendons compared with collagen-only or control tendons. Conclusion: Mechanical and histologic results suggested that healing in the PEP-treated group favored intrinsic healing (absence of adhesions) while control animals and animals treated with collagen only healed primarily via extrinsic scar formation. Despite a smaller cross-sectional area, treated tendons had the same ultimate tensile stress. This pilot investigation shows promise for PEP as a means of effectively treating tendon injuries and enhancing intrinsic healing. Clinical Relevance: The production of a cell-free, off-the-shelf product that can promote tendon regeneration would provide a viable solution for physicians and patients to enhance tendon healing and decrease adhesions as well as shorten the time required to return to work or sports.

Original languageEnglish (US)
JournalOrthopaedic Journal of Sports Medicine
Issue number12
StatePublished - Dec 17 2021


  • exosomes
  • growth factors/healing enhancement
  • injury prevention
  • tendon biomechanics
  • tendon healing
  • tissue engineering

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine


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