An experimental setup to evaluate innovative therapy options for the enhancement of bone healing using BMP as a benchmark--a pilot study

Eur Cell Mater. 2012 Apr 10:23:262-71; discussion 271-2. doi: 10.22203/ecm.v023a20.

Abstract

Critical or delayed bone healing in rat osteotomy (OT) models is mostly achieved through large defects or instability. We aimed to design a rat OT model for impaired bone healing based on age, gender and parity. The outcome should be controllable through variations of the haematoma in the OT including a bone morphogenetic protein (BMP) 2 guided positive control. Using external fixation to stabilise femoral a 2 mm double OT in 12 month old, female Sprague Dawley rats after a minimum of 3 litters healing was characterised following in situ haematoma formation (ISH-group)), transplantation of a BMP charged autologous blood clot (BMP-group) and the artificial blood clot only (ABC-group) into the OT-gap. In vivo micro-computer tomography (µCT) scans were performed after 2, 4 and 6 weeks. After 6 weeks specimens underwent histological analyses. In µCT examinations and histological analyses no bony bridging was observed in all but one animal in the ISH-group. In the BMP group complete bridging was achieved in all animals. The ABC-group showed less mineralised tissue formation and smaller bridging scores during the course of healing than the ISH-group. In this pilot study we introduce a model for impaired bone healing taking the major biological risk factors into account. We could show that the in situ fracture haematoma is essential for bone regeneration. Using BMP as a positive control the presented experimental setup can serve to evaluate innovative therapeutical concepts in long bone application.

MeSH terms

  • Animals
  • Benchmarking
  • Blood Coagulation / drug effects
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Bone Regeneration / drug effects
  • Female
  • Femur / diagnostic imaging
  • Femur / physiology
  • Femur / surgery*
  • Models, Animal
  • Osteotomy / methods*
  • Pilot Projects
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Wound Healing / drug effects*
  • X-Ray Microtomography / methods

Substances

  • Bone Morphogenetic Protein 2