Effects of FGF-2 Concentration on Regenerated Dentin Structures

Objective: It is well known that FGF-2 promotes proliferation and differentiation of a variety of cells. Recently, we demonstrated that controlled release of FGF-2 from gelatin hydrogels induces dentin-like particles in a dentin defect above exposed pulp of rat molars. In the present study, we analyzed an optimal concentration of FGF-2 to induce appropriate amount and structure of regenerated dentin. Methods: Wistar rats were anesthetized, after which dental pulp was exposed on occlusal aspects of maxillary first molars. Mixtures of collagen sponge with gelatin hydrogels incorporating several concentrations of FGF-2 (0, 0.05, 0.5, 5.0 mg/ml) were implanted on the exposed pulp. One and three weeks after implantation, isolated molars were fixed, and demineralized. Serial sections were stained with hematoxylin and eosin for histological analysis. Results: One week after implantation, implanted mixtures in dentin defects of all groups were invaded by pulp tissue including pulp cells and microvessels. Invasion of microvessels and pulp cells were frequently observed in the mixture containing gelatin hydrogels incorporating 0.5 mg/ml FGF-2. Three weeks after implantation, calcified structures were observed in dentin defects implanted mixtures with gelatin hydrogels incorporating 0.5 and 5.0mg/ml FGF-2. We found that the calcified structure regenerated by controlled release of 0.5 mg/ml FGF-2 showed dentin bridge like structure, whereas dentin-like particles was induced by the controlled release of 5.0 mg/ml FGF-2. Conclusion: Our results suggest that the regeneration of dentin above exposed pulp depends on the concentration of FGF-2 incorporated into gelatin hydrogels, and that lower concentration (0.5 mg/ml) of FGF-2 incorporated into gelatin hydrogels may be more suitable than higher concentration (5.0 mg/ml) of FGF-2 for regenerated dentin with the natural sound dentin structures. Supported by Grants (18592094, 18209057) from The Ministry of Education, Science, and Culture of Japan, Tokyo, Japan.