Controlled release of fibroblast growth factor 2 stimulates bone healing in an animal model of diabetes mellitus.
OBJECTIVE
Bone formation and the healing of calvarial defects in mice is diminished in chemically induced type 1 diabetes. The present study investigated whether controlled local release of fibroblast growth factor 2 (FGF-2) stimulates bone defect healing in this model of diabetes.


METHODS
First, in vitro release kinetics of different doses of recombinant human FGF-2 (rhFGF-2) from polyglycolate:polylactide membranes was determined over a 14-day period by incubating loaded membranes in PBS with constant shaking. The amount of FGF-2 was measured by enzyme-linked immunosorbent assay. Then, the effects of rhFGF-2-loaded and control membranes on calvarial defect healing over a 14-day healing period were determined in diabetic and nondiabetic mice. The degree of healing was determined by histomorphometric analyses of bone area percentage and by area measurements. The significance of the data was determined by statistical analyses, including analysis of variance.


RESULTS
Kinetic release data in vitro showed that membranes loaded with 5 microg FGF-2 released measurable levels of growth factor for more than 14 days. Data from the in vivo study supported the previous finding that diabetes inhibits bone formation. Membranes containing rhFGF-2 significantly (P < .05) stimulated bone formation in diabetic animals to near normal levels during the healing period.


CONCLUSIONS
FGF-2-loaded membranes may be useful in further studies aimed at developing therapeutic strategies for correcting deficient bone healing in patients with diabetes.
Santana
Ronaldo B
RB
Department of Periodontology, Dental School, Universidade Federal Fluminense, Niteroi, Rio de Janeiro, Brazil.
Trackman
Philip C
PC
D020341:Absorbable Implants; D000704:Analysis of Variance; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D048091:Guided Tissue Regeneration / Q000379:methods*; D006801:Humans; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D012886:Skull / Q000601:surgery; D018709:Statistics, Nonparametric; D013311:Streptozocin
D008567:Membranes, Artificial; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D013311:Streptozocin