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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 12 - 2024 | doi: 10.3389/fbioe.2024.1407729

Collagen scaffold-seeded iTenocytes accelerate the healing and functional recovery of Achilles tendon defects in a rat model

Provisionally accepted
Thomas Thomas Später Thomas Thomas Später 1,2Patricia Del Rio Patricia Del Rio 1,2Oksana Shelest Oksana Shelest 2Jacob Tyler Wechsler Jacob Tyler Wechsler 1,2Giselle Kaneda Giselle Kaneda 1,2Melissa Chavez Melissa Chavez 1,2Julia Sheyn Julia Sheyn 1,2Victoria Yu Victoria Yu 1,2Wolfgang Metzger Wolfgang Metzger 3Dave Huang Dave Huang 4,5Melodie Metzger Melodie Metzger 4,5Wafa Tawackoli Wafa Tawackoli 1,2,5,6,7Dmitriy Sheyn Dmitriy Sheyn 1,2,5,8,9*
  • 1 Orthopedic Stem Cell Research Laboratory, Cedars Sinai Medical Center, Los Angeles, California, United States
  • 2 Regenerative Medicine Institute, Cedars Sinai Medical Center, Los Angeles, California, United States
  • 3 Department of Trauma, Hand and Reconstructive Surgery, Saarland University, Homburg, Germany
  • 4 Orthopedics Biomechanics Laboratory, Cedars-Sinai Medical Center, Los Angeles, United States
  • 5 Department of Orthopaedics, Cedars Sinai Medical Center, Los Angeles, California, United States
  • 6 Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, United States
  • 7 Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, United States
  • 8 Department of Surgery, Cedars Sinai Medical Center, Los Angeles, California, United States
  • 9 Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, United States

The final, formatted version of the article will be published soon.

    Tendon injuries represent an ongoing challenge in clinical practice due to poor regenerative capacity, structure, and biomechanical function recovery of ruptured tendons. This study is focused on the assessment of a novel strategy to repair ruptured Achilles tendons in a Nude rat model using stem cellseeded biomaterial. Specifically, we have used induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) overexpressing the early tendon marker Scleraxis (SCX, iMSC SCX+ , iTenocytes) in combination with an elastic collagen scaffold. Achilles tendon defects in Nude rat models were created by isolating the tendon and excising 3mm of the midsection. The Achilles tendon defects were then repaired with iTenocyte-seeded scaffolds, unseeded scaffolds, or suture only and compared to native Nude rat tendon tissue using gait analyses, biomechanical testing, histology, and immunohistochemistry. The results show faster functional recovery of gait in iTenocyte-seeded scaffold group comparing to scaffold only and suture only groups. Both iTenocyte-seeded scaffold and scaffold only treatment groups had improved biomechanical properties when compared to suture only treatment group, however no statistically significant difference was found in comparing the cell seeding scaffold an scaffold only group in terms of biomechanical properties. Immunohistochemistry staining further demonstrated that iTenocytes successfully populated the collagen scaffolds and survived 9 weeks after implantation in vivo. Additionally, the repaired tissue of iTenocyte-treated injuries exhibited a more organized structure when compared to tendon defects that were repaired only with

    Keywords: Tissue Regeneration, Stem Cells, Collagen scaffold, Achilles tendon rupture repair, Tissue Engineering

    Received: 27 Mar 2024; Accepted: 14 Nov 2024.

    Copyright: © 2024 Thomas Später, Del Rio, Shelest, Wechsler, Kaneda, Chavez, Sheyn, Yu, Metzger, Huang, Metzger, Tawackoli and Sheyn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Dmitriy Sheyn, Orthopedic Stem Cell Research Laboratory, Cedars Sinai Medical Center, Los Angeles, 90048, California, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.