Sustained delivery of transforming growth factor beta three enhances tendon-to-bone healing in a rat model

J Orthop Res. 2011 Jul;29(7):1099-105. doi: 10.1002/jor.21301. Epub 2011 Jan 18.

Abstract

Despite advances in surgical technique, rotator cuff repairs are plagued by a high rate of failure. This failure rate is in part due to poor tendon-to-bone healing; rather than regeneration of a fibrocartilaginous attachment, the repair is filled with disorganized fibrovascular (scar) tissue. Transforming growth factor beta 3 (TGF-β3) has been implicated in fetal development and scarless fetal healing and, thus, exogenous addition of TGF-β3 may enhance tendon-to-bone healing. We hypothesized that: TGF-β3 could be released in a controlled manner using a heparin/fibrin-based delivery system (HBDS); and delivery of TGF-β3 at the healing tendon-to-bone insertion would lead to improvements in biomechanical properties compared to untreated controls. After demonstrating that the release kinetics of TGF-β3 could be controlled using a HBDS in vitro, matrices were incorporated at the repaired supraspinatus tendon-to-bone insertions of rats. Animals were sacrificed at 14-56 days. Repaired insertions were assessed using histology (for inflammation, vascularity, and cell proliferation) and biomechanics (for structural and mechanical properties). TGF-β3 treatment in vivo accelerated the healing process, with increases in inflammation, cellularity, vascularity, and cell proliferation at the early timepoints. Moreover, sustained delivery of TGF-β3 to the healing tendon-to-bone insertion led to significant improvements in structural properties at 28 days and in material properties at 56 days compared to controls. We concluded that TGF-β3 delivered at a sustained rate using a HBDS enhanced tendon-to-bone healing in a rat model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena / drug effects
  • Biomechanical Phenomena / physiology
  • Bone and Bones / physiology*
  • Cicatrix / prevention & control
  • Disease Models, Animal
  • Drug Delivery Systems / methods
  • Injections, Intralesional / methods
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Rotator Cuff Injuries
  • Rotator Cuff* / drug effects
  • Rotator Cuff* / physiology
  • Tendon Injuries / drug therapy*
  • Tendon Injuries / physiopathology
  • Transforming Growth Factor beta3 / pharmacokinetics
  • Transforming Growth Factor beta3 / pharmacology*
  • Wound Healing / drug effects*
  • Wound Healing / physiology

Substances

  • Transforming Growth Factor beta3