Increasing vascularity to improve healing of a segmental defect of the rat femur

Rena Stewart, Jessica Goldstein, Alan Eberhardt, Gabe Tien Min Gabriel Chu, Shawn Gilbert

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Background: Segmental bone loss remains a challenging clinical problem.A frequent mitigating factor is inadequate blood supply. Small molecules that activate the hypoxia-inducible factor pathway can be used to stimulate angiogenesis. We investigated an approach to promote healing using angiogenic and osteogenic compounds in combination with a biodegradable, weightbearing scaffold. Methods: Adult rats underwent removal of a 5-mm segment of femur stabilized by a cylindrical biodegradable implant and intramedullary fixation. Treatment groups included 1) saline (negative control); 2) desferrioxamine (DFO, a hypoxia-inducible factor activator; 3) low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) (5 μg); 4) DFO and low-dose rhBMP-2 (5 μg); or 5) rh-BMP-2 (10 μg). Angiography was used to evaluate vascularity. Bone healing was assessed by radiographs, microcomputed tomography, histology, and biomechanical testing. Results: Increased vascularity was seen at 6 weeks in the DFO treatment group. There appeared to be increased bone bridging as assessed by radiographic scores and microcomputed tomography in the BMP groups, although the quantification of bone volume did not show statistically significant differences. Biomechanical testing revealed improved stiffness in the treatment groups. Conclusions: DFO improved angiogenesis and stiffness of bone healing in segmental defects. BMP improved radiographic scores and stiffness. Use of angiogenic compounds in segmental bone loss is promising. Clinical Relevance: Activation of the hypoxia-inducible factor pathway may prove useful for bone defects, particularly where impaired blood supply exists.The low-cost approach could be useful in segmental bone defects clinically.

Original languageEnglish (US)
Pages (from-to)472-476
Number of pages5
JournalJournal of orthopaedic trauma
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2011

Keywords

  • desferrioxamine
  • hypoxia-inducible factor
  • polypropylene fumarate
  • segmental defect

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

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