Improved tendon healing using bFGF, BMP-12 and TGFβ1 in a rat model

Eur Cell Mater. 2018 Jun 13:35:318-334. doi: 10.22203/eCM.v035a22.

Abstract

Several growth factors (GFs) are expressed as tendons heal, but it remains unknown whether their combined application enhances the healing process. This matter was addressed by applying a combination of basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12) and transforming growth factor beta 1 (TGFβ1) in a rat Achilles tendon transection model. GFs were applied in one of the three following ways: i) direct application of all three factors at the time of surgery; ii) sequential, tiered percutaneous injection of individual factors immediately after surgery, 48 h and 96 h later; iii) load of all three factors onto a collagen sponge implanted at the time of surgery. After 1, 2, 4 and 8 weeks, healing was assessed based on tendon length and thickness, mechanical strength, stiffness and histology. Best results were achieved when GFs were loaded onto a collagen sponge - with a rapid increase in mechanical strength (load to failure, 71.2 N vs. 7.7 N in controls), consistent tendon length over time (9.9 mm vs. 16.2 mm in controls) and faster tendon remodelling, as measured by histology - followed by tiered injection therapy over 96 h. In conclusion, implantation of a GF-loaded collagen sponge could provide a promising treatment, especially in high-performance athletes and revision cases prone to re-rupture. For conservative treatment, tiered percutaneous GF application could be an option for improving clinical outcome.

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Bone Morphogenetic Proteins / pharmacology*
  • Collagen / metabolism
  • Fibroblast Growth Factor 2 / pharmacology*
  • Horses
  • Male
  • Rats, Sprague-Dawley
  • Tendons / pathology*
  • Tendons / surgery
  • Transforming Growth Factor beta1 / pharmacology*
  • Weight-Bearing
  • Wound Healing / drug effects*

Substances

  • Bone Morphogenetic Proteins
  • Transforming Growth Factor beta1
  • growth differentiation factor 7
  • Fibroblast Growth Factor 2
  • Collagen