Biomechanical, Histologic, and Molecular Evaluation of Tendon Healing in a New Murine Model of Rotator Cuff Repair

Arthroscopy. 2018 Apr;34(4):1173-1183. doi: 10.1016/j.arthro.2017.10.045. Epub 2018 Feb 16.

Abstract

Purpose: To develop a clinically relevant, robust murine model of rotator cuff tendon repair to examine cellular and molecular mechanisms of healing.

Methods: Sixty C57BL/6 male mice underwent rotator cuff transection and repair using microsurgical techniques. A modified Kessler suturing technique was used prior to tendon detachment. Sutures were passed through 2 intersecting bone tunnels that were made at the tendon attachment site. Mice were sacrificed at 2 and 4 weeks with subsequent biomechanical, histologic, micro-CT, and gene expression evaluations.

Results: Failure forces in the 2- and 4-week groups were 36% and 75% of the intact tendon, respectively. Histologic evaluation revealed complete reattachment of the tendon with no observable gap. Healing occurred by formation of fibrovascular tissue at the tendon-bone interface, similar to larger animal models. Molecular analysis revealed gene expression consistent with gradual healing of the reattached tendon over a period of 4 weeks. Comparisons were made using 1-way analysis of variance.

Conclusions: This model is distinguished by use of microsurgical suturing techniques, which provides a robust, reproducible, and economic animal model to study various aspects of rotator cuff pathology.

Clinical relevance: Improvement of clinical outcomes of rotator cuff pathology requires in-depth understanding of the underlying cellular and molecular mechanisms of healing. This study presents a robust murine model of supraspinatus repair to serve as a standard research tool for basic and translational investigations into signaling pathways, gene expression, and the effect of biologic augmentation approaches.

Publication types

  • Video-Audio Media

MeSH terms

  • Aggrecans / genetics
  • Aggrecans / metabolism
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomechanical Phenomena / physiology
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Gene Expression
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Rotator Cuff / diagnostic imaging*
  • Rotator Cuff / pathology*
  • Rotator Cuff / physiopathology
  • Rotator Cuff Injuries / diagnostic imaging
  • Rotator Cuff Injuries / surgery*
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • Suture Techniques
  • Tensile Strength / physiology
  • Wound Healing
  • X-Ray Microtomography

Substances

  • Aggrecans
  • Basic Helix-Loop-Helix Transcription Factors
  • Collagen Type I
  • RNA, Messenger
  • SOX9 Transcription Factor
  • Scx protein, mouse
  • Sox9 protein, mouse
  • Matrix Metalloproteinases