title: Increasing vascularity to improve healing of a segmental defect of the rat femur.
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.
  
  
  CONCLUSIONS
  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.
authors: Division of Orthopaedics, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors: Rena
authors: R
authors: Stewart
authors: Jessica
authors: J
authors: Goldstein
authors: Alan
authors: A
authors: Eberhardt
authors: Gabe Tien-Min Gabriel
authors: GT
authors: Chu
authors: Shawn
authors: S
authors: Gilbert
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D003676:Deferoxamine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019338:Polypharmacy; D011859:Radiography; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D043925:Angiogenesis Inducing Agents; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003676:Deferoxamine