Formation of dentinal bridge on surface of regenerated dental pulp in dentin defects by controlled release of fibroblast growth factor-2 from gelatin hydrogels.

INTRODUCTION: Pulp regeneration therapy is important to overcome the limitations of conventional therapy to induce reparative dentinogenesis. In the present study, we examined the effects of controlled release of different dosages of fibroblast growth factor-2 (FGF-2) from gelatin hydrogels to regenerate the dentin-pulp complex. METHODS: After the amputation of dental pulp of rat molars, gelatin hydrogels incorporating various dosages of FGF-2 were individually implanted into dentin defects above the sites of the amputated pulps. Histologic changes as well as the expression of dentin matrix protein-1 (DMP-1) and nestin in the dentin defect area above the amputated pulp were analyzed. RESULTS: We found that controlled release of high doses of FGF-2 from gelatin hydrogels induced DMP-1-positive calcified particles in the proliferating pulp, whereas a moderate dose of FGF-2 induced DMP-1-positive dentinal bridge on the surface of the proliferating pulp. These findings indicate that the dosage of released FGF-2 has an influence on the structure of calcified tissue regenerated in dentin defects. In addition, pulp cells near calcified tissues regenerated in dentin defects were nestin-negative, suggesting that the calcified tissues might be osteodentin. CONCLUSIONS: Our results showed that the dentin regeneration on amputated pulp, not reparative dentin formation toward amputated pulp, can be regulated by adjusting the dosage of FGF-2 incorporated in biodegradable gelatin hydrogels.

Formation of dentin-like particles in dentin defects above exposed pulp by controlled release of fibroblast growth factor 2 from gelatin hydrogels.

The induction of dentin formation on exposed dental pulp is a major challenge in research on the regeneration of the dentin-pulp complex. We examined the effects of fibroblast growth factor 2 (FGF2), which was delivered in either a collagen sponge (noncontrolled release) or incorporated into gelatin hydrogels (controlled release), on the formation of dentin in exposed rat molar pulps. During the early phase of pulp wound healing, pulp cell proliferation and invasion of vessels into dentin defects above exposed pulp were induced in both groups. In the late phase, the induction of dentin formation was distinctly different between the 2 types of FGF2 release. The noncontrolled release of free FGF2 from collagen sponge induced excessive reparative dentin formation in the residual dental pulp, although dentin defects were not noted. In contrast, controlled release of FGF2 from gelatin hydrogels induced the formation of dentin-like particles with dentin defects above exposed pulp. These results suggest the possibility of a novel therapeutic approach for dentin-pulp complex by controlled release of bioactive FGF2.