Fibroblast Growth Factor-2 and Enamel Matrix Derivative Enhance Proliferation, Migration, and Wound Healing in...

Background and Objectives: Soft-tissue healing, particularly rapid epithelialization, is a critical determinant of successful periodontal regenerative therapy. Fibroblast growth factor-2 (FGF-2) and enamel matrix derivative (EMD) are regenerative biomaterials used clinically. However, their comparative effects on gingival epithelial and fibroblast cell behavior remain unclear. The objective of this study was to examine the effects of FGF-2 on the proliferation, migration, and wound closure dynamics of human gingival epithelial-like cells (Ca9-22) and human gingival fibroblasts (HGF-1) and to compare its effects with those of EMD. Materials and Methods: Ca9-22 and HGF-1 cells were stimulated with FGF-2 (10 µg/mL) or EMD (100 µg/mL) or left unstimulated (control). Wound closure was assessed via scratch assay, migratory capacity via Transwell assay, and proliferation via automated cell counting at pre-defined time points. Results: In Ca9-22 cells, both FGF-2 and EMD significantly accelerated wound closure in a time- and concentration-dependent manner and markedly enhanced cell migration and proliferation compared to controls. EMD consistently induced a stronger migratory response. In HGF-1 cells, FGF-2 significantly advanced wound closure by day 5, whereas EMD induced a non-significant favorable trend. Both treatments significantly increased cell proliferation and migration of HGF-1 cells, with EMD yielding the highest migratory cell count. Conclusions: FGF-2 promotes gingival soft-tissue healing by enhancing epithelial-like cell and fibroblast migration and proliferation, supporting rapid epithelialization. EMD produced comparable wound-healing effects, indicating that the activation of both epithelial and mesenchymal cells is a central mechanism shared by distinct regenerative agents.