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

Autor:	Wellings EP; Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA., Huang TC; Division of Plastic Surgery, Mayo Clinic, Rochester, Minnesota, USA., Li J; Division of Plastic Surgery, Mayo Clinic, Rochester, Minnesota, USA., Peterson TE; Department of Regenerative Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Van Cleve Cardiac Regeneration Medicine Program, Mayo Clinic, Rochester, Minnesota, USA., Hooke AW; Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA., Rosenbaum A; Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA., Zhao CD; Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA., Behfar A; Department of Regenerative Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Van Cleve Cardiac Regeneration Medicine Program, Mayo Clinic, Rochester, Minnesota, USA., Moran SL; Division of Plastic Surgery, Mayo Clinic, Rochester, Minnesota, USA., Houdek MT; Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Jazyk:	angličtina
Zdroj:	Orthopaedic journal of sports medicine [Orthop J Sports Med] 2021 Dec 17; Vol. 9 (12), pp. 23259671211062929. Date of Electronic Publication: 2021 Dec 17 (Print Publication: 2021).
DOI:	10.1177/23259671211062929
Abstrakt:	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. Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was funded by the Orthopedic Research Review Committee (ORRC) as well as the Obaid Vascularized Composite Tissue Award (E.P.W, S.L.M., M.T.H.). All PEP vials were manufactured and supplied by Rion LLC at the Advanced Product Incubator (API) at Mayo Clinic. A.R. has received hospitality payments from Medtronics. A.B. has received hospitality payments from Abiomed. S.L.M. has received consulting fees from Ascension Orthopedics and Integra LifeSciences, nonconsulting fees from Integra LifeSciences, and royalties from Integra LifeSciences. M.T.H. has received consulting fees from Daiichi Sankyo and hospitality payments from Linkbio, Medical Device Business Services, Stryker, and Zimmer Biomet. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. (© The Author(s) 2021.)
Databáze:	MEDLINE
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