Skull bone regeneration in primates in response to basic fibroblast growth factor.
OBJECTIVE
The feasibility of using a biodegradable hydrogel incorporating basic fibroblast growth factor (bFGF) to induce bone regeneration at the site of a skull defect in monkeys was investigated.


METHODS
Basic fibroblast growth factor was incorporated into a bioabsorbable hydrogel, which was prepared through glutaraldehyde crosslinking of gelatin. Following treatment of monkey skull defects measuring 6 mm in diameter (six defects/experimental group) with gelatin hydrogel incorporating bFGF, skull bone regeneration was evaluated using soft x-ray studies, dual x-ray absorptometry, and histological examinations. The water content of the hydrogels varied according to the glutaraldehyde concentration in the hydrogel preparation. Gelatin hydrogels incorporating 100 microg of bFGF significantly promoted bone regeneration and the skull defect was completely closed 21 weeks after implantation. This is in marked contrast with the effect of the same dose of bFGF in solution form. Bone mineral density (BMD) measured at the sites of skull defect was enhanced by the bFGF-incorporating hydrogels. The BMD enhancement was more prominent at lower water contents of hydrogel. Empty gelatin hydrogels neither induced nor interfered with skull bone regeneration.


CONCLUSIONS
The findings of this study indicate that bFGF coupled with bioabsorbable hydrogel is a very promising tool to assist in the regrowth of bone at the site of a skull defect, which clinically has been recognized as almost impossible.
Tabata
Y
Y
Institute for Frontier Medical Sciences and Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Japan.
Yamada
K
K
Hong
L
L
Miyamoto
S
S
Hashimoto
N
N
Ikada
Y
Y
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling / Q000187:drug effects*; D004338:Drug Combinations; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005780:Gelatin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D008252:Macaca fascicularis; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology*; D014867:Water
D004338:Drug Combinations; D014867:Water; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin