Recombinant human platelet-derived growth factor-BB augmentation of new-bone formation in a rat model of distraction osteogenesis.
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-microL 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 microg/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 microg/mL rhPDGF-BB groups, respectively), whereas on Day 42 regenerate bone volume was significantly greater in the 300 and 1000 microg/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 microg/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.
Moore
Douglas C
DC
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, USA.
Ehrlich
Michael G
MG
McAllister
Scott C
SC
Machan
Jason T
JT
Hart
Charles E
CE
Voigt
Clifford
C
Lesieur-Brooks
Anne M
AM
Weber
Elizabeth W
EW
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D001861:Bone Regeneration / Q000187:drug effects*; D004195:Disease Models, Animal; D017102:Fracture Healing / Q000187:drug effects*; D008297:Male; D019857:Osteogenesis, Distraction; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley
D043925:Angiogenesis Inducing Agents; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin