Mesenchymal Stem Cell Delivery via Topographically Tenoinductive Collagen Biotextile Enhances Regeneration of Segmental Tendon Defects

Am J Sports Med. 2022 Jul;50(8):2281-2291. doi: 10.1177/03635465221097939. Epub 2022 Jun 1.

Abstract

Background: Successful management of massive rotator cuff (RC) tendon tears represents a treatment challenge because of the limited intrinsic healing capacity of native tendons and the risk of repair failure. Biologic augmentation of massive RC tears utilizing scaffolds-capable of regenerating bulk tendon tissue to achieve a mechanically functional repair-represents an area of increasing clinical interest.

Purpose: To investigate the histological and biomechanical outcomes after the use of a novel biologic scaffold fabricated from woven electrochemically aligned collagen (ELAC) threads as a suture-holding, fully load-bearing, defect-bridging scaffold with or without mesenchymal stem cells (MSCs) compared with direct repair in the treatment of critically sized RC defects using a rabbit model.

Study design: Controlled laboratory study.

Methods: A total of 34 New Zealand White rabbits underwent iatrogenic creation of a critically sized defect (6 mm) in the infraspinatus tendon of 1 shoulder, with the contralateral shoulder utilized as an intact control. Specimens were divided into 4 groups: (1) gap-negative control without repair; (2) direct repair of the infraspinatus tendon-operative control; (3) tendon repair using ELAC; and (4) tendon repair using ELAC + MSCs. Repair outcomes were assessed at 6 months using micro-computed tomography, biomechanical testing, histology, and immunohistochemistry.

Results: Specimens treated with ELAC demonstrated significantly less tendon retraction when compared with the direct repair group specimens (P = .014). ELAC + MSCs possessed comparable biomechanical strength (178 ± 50 N) to intact control shoulders (199 ± 35 N) (P = .554). Histological analyses demonstrated abundant, well-aligned de novo collagen around ELAC threads in both the ELAC and the ELAC + MSC shoulders, with ELAC + MSC specimens demonstrating increased ELAC resorption (7% vs 37%, respectively; P = .002). The presence of extracellular matrix components, collagen type I, and tenomodulin, indicating tendon-like tissue formation, was appreciated in both the ELAC and the ELAC + MSC groups.

Conclusion: The application of MSCs to ELAC scaffolds improved biomechanical and histological outcomes when compared with direct repair for the treatment of critically sized defects of the RC in a rabbit model.

Clinical relevance: This study demonstrates the feasibility of repairing segmental tendon defects with a load-bearing, collagen biotextile in an animal model, showing the potential applicability of RC repair supplementation using allogeneic stem cells.

Keywords: biologic healing enhancement; rotator cuff; stem cell therapy; tissue engineering.

MeSH terms

  • Animals
  • Biological Products*
  • Biomechanical Phenomena
  • Collagen / metabolism
  • Humans
  • Mesenchymal Stem Cells* / metabolism
  • Rabbits
  • Regeneration
  • Rotator Cuff Injuries* / metabolism
  • Rotator Cuff Injuries* / surgery
  • Tendons / surgery
  • X-Ray Microtomography

Substances

  • Biological Products
  • Collagen