# Fibroblast Growth Factor-2 and Enamel Matrix Derivative Enhance Proliferation, Migration, and Wound Healing in Gingival Epithelial and Fibroblast Cells

**Authors:** Nanako Tsuchimochi, Naoki Maruo, Kimiko Ohgi, Hiroaki Yamato, Masanobu Nakagami, Aya Fujioka, Yasunori Yoshinaga

PMC · DOI: 10.3390/medicina62020244 · 2026-01-23

## TL;DR

This study shows that FGF-2 and EMD improve wound healing in gum cells by boosting cell movement and growth.

## Contribution

The study compares the effects of FGF-2 and EMD on gingival epithelial and fibroblast cells for the first time.

## Key findings

- FGF-2 and EMD both significantly enhance wound closure, migration, and proliferation in Ca9-22 cells.
- EMD induces stronger migratory responses in Ca9-22 cells compared to FGF-2.
- Both FGF-2 and EMD increase proliferation and migration in HGF-1 cells, with EMD showing the highest migration.

## Abstract

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.

## Linked entities

- **Proteins:** FGF2 (fibroblast growth factor 2)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, TGFBR1 (transforming growth factor beta receptor 1) [NCBI Gene 7046] {aka AAT5, ACVRLK4, ALK-5, ALK5, ESS1, LDS1}, SMAD2 (SMAD family member 2) [NCBI Gene 4087] {aka CHTD8, JV18, JV18-1, LDS6, MADH2, MADR2}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, FGF7 (fibroblast growth factor 7) [NCBI Gene 2252] {aka HBGF-7, KGF}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, HGF (hepatocyte growth factor) [NCBI Gene 3082] {aka DFNB39, F-TCF, HGFB, HPTA, SF}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Fgf2 (fibroblast growth factor 2) [NCBI Gene 54250] {aka Fgf-2, Fgf2a, bFGF}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}
- **Diseases:** infection (MESH:D007239), oral squamous cell carcinoma (MESH:D000077195), inflammation (MESH:D007249), periodontitis (MESH:D010518), injury to (MESH:D014947), Tumor (MESH:D009369)
- **Chemicals:** CO2 (MESH:D002245), PBS (MESH:D007854), penicillin (MESH:D010406), phenol red (MESH:D010637), crystal violet (MESH:D005840), Dulbecco's modified Eagle medium (-), Trypan Blue (MESH:D014343), methanol (MESH:D000432), streptomycin (MESH:D013307), EDTA (MESH:D004492)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** Ca9-22 — Homo sapiens (Human), Gingival squamous cell carcinoma, Cancer cell line (CVCL_1102), HGF-1 — Homo sapiens (Human), Finite cell line (CVCL_B5XD)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942401/full.md

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Source: https://tomesphere.com/paper/PMC12942401