Recombinant Human Platelet-Derived Growth Factor-BB Augmentation of New-Bone Formation in a Rat Model of Distraction Osteogenesis

Moore, Douglas C.; Ehrlich, Michael G.; McAllister, Scott C.; Machan, Jason T.; Hart, Charles E.; Voigt, Clifford; Lesieur-Brooks, Anne M.; Weber, Elizabeth W.
August 2009
Journal of Bone & Joint Surgery, American Volume;Aug2009, Vol. 91-A Issue 8, p1973
Academic Journal
Background: Distraction osteogenesis creates a challenging bone-healing environment with protracted demand for cells of the osteoblast lineage. Platelet-derived growth factor-BB (PDGF-BB) is an osteoblast mitogen and chemotaxin that has been shown to accelerate and/or enhance bone-healing in several preclinical studies. The purpose of the present study was to determine whether recombinant human platelet-derived growth factor-SB (rhPDGF-BB) would have a similar effect on regenerate healing after distraction osteogenesis. Methods: Unilateral 7-mm mid-diaphyseal femoral lengthening procedures were performed in eighty-three male Sprague-Dawley rats that were separated into five experimental groups. During the distraction period (Days 7 to 28), each animal received a weekly 50-μL injection of either sodium acetate buffer, bovine collagen dissolved in sodium acetate buffer, or one of three concentrations of rhPDGF-BB (100, 300, or 1000 μg/mL) into the distraction site. Animals from each group were killed on Days 35, 42, 49, 56, and 63. Healing was assessed with biweekly serial radiographs, micro-computed tomography of the explanted bones, and histologic analysis. Results: rhPDGF-BB treatment significantly increased new-bone formation at the midconsolidation time points (Days 42, 49, and 56) as well as the union rate. On Day 49 regenerate bone volume was significantly greater in each of the three rhPDGF-BB-treated groups than in the controls (p <0.05, p = 0.0002, and p < 0.05 for the 100, 300, and 1000 μg/mL rhPDGF-BB groups, respectively), whereas on Day 42 regenerate bone volume was significantly greater in the 300 and 1000 μg/mL rhPDGF-BB groups than in the controls (p = 0.0002 and p < 0.05, respectively) and on Day 56 regenerate bone volume was significantly greater in the 100 and 300 μg/mL rhPDGF-BB groups than in the controls (p < 0.05 and p < 0.0001, respectively). The overall union rate was 40.4% (nineteen of forty-seven) in the rhPDGF-BB- treated animals, compared with 4.5% (one of twenty-two) in the controls (p = 0.01). The radiographic and histologic results were consistent with new-bone formation as quantified by micro-computed tomography, although they were less definitive. Conclusions: The administration of exogenous rhPDGF-BB into the distraction site during diaphyseal distraction enhanced bone-healing in a rat model of distraction osteogenesis as evidenced by both increased regenerate new-bone formation and a higher union rate. Clinical Relevance: The ability of rhPDGF-BB to enhance healing in this model suggests that it may be able to shorten treatment time and to decrease the nonunion rate in the challenging healing environment created during distraction osteogenesis.


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