Recombinant Human Platelet-Derived Growth Factor BB (rhPDGF-BB) and Beta-Tricalcium Phosphate/Collagen Matrix Enhance Fracture Healing in a Diabetic Rat Model

ABSTRACT: Diabetesmellitus is a common systemic disease that has been associatedwith poor fracture healing outcomes. Themechanism throughwhichdiabetes impairsbone regeneration isunknown.Onepossiblemechanismmaybe related to eitherdecreasedoruncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet-derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGFmay overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 mg) and high (75 ug) doses of recombinant human PDGF-BB (rhPDGF-BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle-treated animals. rhPDGF-BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF-BB treatment significantly increased callus peak torque values (p<0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF-BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF-BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF-BB may be a new therapeutic approach to treat diabetes-impaired fracture healing. 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Re