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

Thomas Später; Patricia Del Rio; Oksana Shelest; Jacob T Wechsler; Giselle Kaneda; Melissa Chavez; Julia Sheyn; Victoria Yu; Wolfgang Metzger; Dave Huang; Melodie Metzger; Wafa Tawackoli; Dmitriy Sheyn

doi:10.3389/fbioe.2024.1407729

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

Front Bioeng Biotechnol. 2024 Dec 6:12:1407729. doi: 10.3389/fbioe.2024.1407729. eCollection 2024.

Authors

Thomas Später^#^{1

2}, Patricia Del Rio^#^{1

2}, Oksana Shelest², Jacob T Wechsler^{1

2}, Giselle Kaneda^{1

2}, Melissa Chavez^{1

2}, Julia Sheyn^{1

2}, Victoria Yu^{1

2}, Wolfgang Metzger³, Dave Huang^{4

5}, Melodie Metzger^{4

5}, Wafa Tawackoli^{1

2

5

6

7}, Dmitriy Sheyn^{1

2

4

5

6

7}

Affiliations

¹ Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
² Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
³ Department of Trauma, Hand and Reconstructive Surgery, Saarland University, Homburg, Germany.
⁴ Orthopedics Biomechanics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
⁵ Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
⁶ Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
⁷ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, United States.

^# Contributed equally.

Abstract

Introduction: 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 cell-seeded biomaterial.

Methods: 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 3 mm 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.

Results: 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 suturing or unseeded scaffolds.

Conclusion: We suggest that iTenocyte-seeded DuRepair™ collagen scaffold can be used as potential treatment to regenerate the tendon tissue biomechanically and functionally.

Keywords: Achilles tendon rupture repair; collagen scaffold; stem cells; tissue engineering; tissue regeneration.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by NIH K01AR071512, CIRM DISC0-14350, and PD was funded by CIRM Bridges.