Recombinant human platelet-derived growth factor BB (rhPDGF-BB) and beta-tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model.
Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated 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 PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 microg) 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.
Al-Zube
Loay
L
UMDNJ- New Jersey Medical School and Graduate School of Biomedical Sciences, Newark, New Jersey, USA.
Breitbart
Eric A
EA
O'Connor
J Patrick
JP
Parsons
J Russell
JR
Bradica
Gino
G
Hart
Charles E
CE
Lin
Sheldon S
SS
D000818:Animals; D000077214:Becaplermin; D001696:Biomechanical Phenomena; D002146:Bony Callus / Q000033:anatomy & histology / Q000254:growth & development; D002130:Calcium Phosphates / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005264:Femoral Fractures / Q000188:drug therapy / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011913:Rats, Inbred BB; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
D002130:Calcium Phosphates; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D003094:Collagen; C018392:tricalcium phosphate