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Scientific Articles   |    
Recombinant Human Platelet-Derived Growth Factor-BB Augmentation of New-Bone Formation in a Rat Model of Distraction Osteogenesis
Douglas C. Moore, MS1; Michael G. Ehrlich, MD1; Scott C. McAllister, BS1; Jason T. Machan, PhD2; Charles E. Hart, PhD3; Clifford Voigt, BA1; Anne M. Lesieur-Brooks, BS1; Elizabeth W. Weber, MD1
1 Orthopaedic Research Laboratories, Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, CORO West Suite 404, 1 Hoppin Street, Providence, RI 02905. E-mail address for M.G. Ehrlich: Michael_Ehrlich@brown.edu
2 Research Statistics, Rhode Island Hospital, 593 Eddy Street, Grads Dorm 206a, Providence, RI 02903
3 9451 Appleton Court, Brentwood, TN 37027
View Disclosures and Other Information
Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from BioMimetic Therapeutics, Inc. In addition, one or more of the authors or a member of his or her immediate family received, in any one year, payments or other benefits in excess of $10,000 or a commitment or agreement to provide such benefits from a commercial entity (BioMimetic Therapeutics, Inc). No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.
Investigation performed at Orthopaedic Research Laboratories, Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island

The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2009 Aug 01;91(8):1973-1984. doi: 10.2106/JBJS.H.00540
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Abstract

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-BB (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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    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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