Intrinsic Tendon Regeneration After Application of Purified Exosome Product: An In Vivo Study. Issue 12 (17th December 2021)

• Record Type: Journal Article
• Authors: Wellings, Elizabeth P.; Huang, Tony Chieh-Ting; Li, Jialun; Peterson, Timothy E.; Hooke, Alexander W.; Rosenbaum, Andrew; Zhao, Chunfeng D.; Behfar, Atta; Moran, Steven L.; Houdek, Matthew T.
• Is Part Of: Orthopaedic journal of sports medicine. Volume 9:Issue 12(2021)
• Publication Date: 2021-12-17
• Subjects: tendon healing -- exosomes -- tendon biomechanics -- growth factors/healing enhancement -- tissue engineering -- injury prevention; Sports medicine -- Periodicals; Orthopedics -- Periodicals; Arthroscopy -- Periodicals; Arthroplasty -- Periodicals; Knee -- Surgery -- Periodicals; 616.7
• DOI: 10.1177/23259671211062929
• Languages: English
• ISSNs: 2325-9671

Abstract

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 × 10 12 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.