Usefulness of Controlled Release of Growth Factors in Investigating the Early Events of Dentin-pulp Regeneration

Introduction: Little information is yet available on the signals involved in progenitor cell migration that precede reparative dentin synthesis. Our aim was to investigate the effect of the controlled release of fibroblast growth factor (FGF)-2 and transforming growth factor beta 1 (TGF-beta 1) on permanent teeth pulp cell proliferation and progenitor cell migration. Methods: FGF-2 and TGF-beta 1 were encapsulated into a biodegradable polymer matrix of lactide and glycolide. Human pulp cells were prepared from third molars, and progenitor cells were sorted by STRO-1. The synthesized microsphere toxicity was checked with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. The growth factor release kinetics were checked by an enzyme-linked immunosorbent assay while maintaining their biological activity and were evaluated by investigating their effects on pulp cell proliferation. Their chemotactic potential was investigated on STRO-1 sorted cells in a migration chamber on Matrigel (Cambrex Bio Science, Walkersville, MD). Results: The cell viability was unaffected by the presence of microspheres. The released amount of FGF-2 and TGF-beta 1 from the microspheres was maintained after 21 days. Increasing the FGF-2 loaded microsphere concentration or the release period significantly increased dental pulp cell proliferation. TGF-beta 1 acted as a potent chemotactic factor of STRO-1 sorted cells. Conclusions: Encapsulating TGF-beta 1 and FGF-2 in a biodegradable polymer of lactide and glycolide microsphere allowed a sustained release of growth factors and provided a protection to their biological activities. Our results clearly show the usefulness of growth factor controlled release in investigating the early events of pulp/dentin. regeneration. It provides additional data on the signals required for vital pulp therapy and future tissue engineering. (J Endod 2013;39:228-235)