Fibrin glue mediated delivery of bone anabolic reagents to enhance healing of tendon to bone

Endre Soreide, Janet M. Denbeigh, Eric A. Lewallen, Rebekah M. Samsonraj, Lawrence J. Berglund, Amel Dudakovic, Simon M. Cool, Lars Nordsletten, Sanjeev Kakar, Andre J van Wijnen

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4 Scopus citations

Abstract

Tendon graft healing in bone tunnels for the fixation of intra-articular ligament reconstructions may limit clinical outcome by delaying healing. This study assesses the effects of hydrogel-mediated delivery of bone anabolic growth factors in a validated model of tendon-to-bone tunnel healing. Forty-five Wistar rats were randomly allocated into three groups (BMP2-treated, GSK126-treated, and placebo). All animals underwent a tendon-to-bone tunnel reconstruction. Healing was evaluated at 4 weeks by biomechanical assessment, micro-computed tomography (bone mineral density, bone volume, cross sectional area of bone tunnels), and traditional histology. Adverse events associated with the hydrogel-mediated delivery of drugs were not observed. Results of our biomechanical assessment demonstrated favorable trends in animals treated with bone anabolic factors for energy absorption (P=0.116) and elongation (P=0.054), while results for force to failure (P=0.691) and stiffness (P=0.404) did not show discernible differences. Cross sectional areas for BMP2-treated animals were reduced, but neither BMP2 nor GSK126 administration altered bone mineral density (P=0.492) or bone volume in the bone tunnel. These results suggest a novel and positive effect of bone anabolic factors on tendon-to-bone tunnel healing. Histological evaluation confirmed absence of collagen fibers crossing the soft tissue-bone interface indicating immature graft integration as expected at this time point. Our study indicates that hydrogel-mediated delivery of BMP2 and GSK126 appears to be safe and has the potential to enhance tendon-to-bone tunnel healing in ligament reconstructions.

Original languageEnglish (US)
JournalJournal of Cellular Biochemistry
DOIs
StateAccepted/In press - Jan 1 2018

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Keywords

  • BMP2
  • Connective tissue
  • GSK126
  • Ligament reconstruction
  • Orthopedic
  • Tendon-to-bone healing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Soreide, E., Denbeigh, J. M., Lewallen, E. A., Samsonraj, R. M., Berglund, L. J., Dudakovic, A., Cool, S. M., Nordsletten, L., Kakar, S., & van Wijnen, A. J. (Accepted/In press). Fibrin glue mediated delivery of bone anabolic reagents to enhance healing of tendon to bone. Journal of Cellular Biochemistry. https://doi.org/10.1002/jcb.26755