# Early Phase Gingival Wound Healing Following Low-Level Er:YAG Laser Irradiation: In Vitro and In Vivo Studies

**Authors:** Lu Chen, Koji Mizutani, Natsumi Saito, Bruna Akinaga Moreira, Daisuke Kido, Takanori Iwata, Akira Aoki

PMC · DOI: 10.3390/dj14030138 · 2026-03-02

## TL;DR

This study shows that low-level Er:YAG laser irradiation can improve early gingival wound healing by reducing inflammation and promoting blood vessel growth.

## Contribution

The study is the first to investigate the effects of low-level Er:YAG laser on both endothelial cell activity and early-phase gingival wound healing in vivo.

## Key findings

- LLLI significantly enhanced cell proliferation without increasing cytotoxicity in vitro.
- Laser irradiation promoted cell migration and reduced inflammation markers in vivo.
- VEGF expression was significantly upregulated, indicating pro-angiogenic effects.

## Abstract

Background: Low-level laser irradiation (LLLI) can promote wound healing. However, the biological effects of the erbium-doped yttrium aluminum garnet (Er:YAG) laser on gingival wound healing remain unclear. Objectives: To assess the effects of low-level Er:YAG laser irradiation on endothelial cell activity in vitro and on early phase gingival wound healing in vivo. Methods: In vitro, human umbilical vein endothelial cells were irradiated with a low-level Er:YAG laser (30 mJ/pulse, 10 Hz, 20 and 30 s, defocused, no water spray) and assessed for viability, cytotoxicity, and migration. Standardized bilateral wounds (4 × 1 mm) were created in the palatal gingiva of 14 male mice using a scalpel and curette. The wounds were irradiated for 20 s under the same irradiation settings, using a contact tip (diameter 800 μm) to induce superficial blood surface coagulation, while contralateral sites were assigned to controls in a split-mouth design. Postoperative wound area and mRNA expression of IL-6, TNF-α, VEGF, FGF-2, and TGF-β1 were analyzed after 48 h. Results: In vitro, LLLI significantly enhanced cell proliferation with/without increasing cytotoxicity. In the wound healing assay, the LLLI significantly promoted cell migration compared with the control. In vivo, the reduction in residual wound area in the laser group was comparable to that in the control group. IL-6 and TNF-α expressions were significantly downregulated, whereas VEGF was significantly upregulated in the laser group. Conclusions: Low-level Er:YAG laser irradiation enhances anti-inflammatory and pro-angiogenic effects, suggesting its potential in promoting gingival wound healing.

## Linked entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569], TNF (tumor necrosis factor) [NCBI Gene 7124], VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422], FGF2 (fibroblast growth factor 2) [NCBI Gene 2247], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Fgf2 (fibroblast growth factor 2) [NCBI Gene 14173] {aka Fgf-2, Fgf2a, Fgfb, bFGF}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Egm2 (egg modifier locus 2) [NCBI Gene 104128], KRT17 (keratin 17) [NCBI Gene 3872] {aka 39.1, CK-17, K17, PC2, PCHC1}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, TM7SF2 (transmembrane 7 superfamily member 2) [NCBI Gene 7108] {aka ANG1, C14SR, DHCR14A, NET47}, ANGPT2 (angiopoietin 2) [NCBI Gene 285] {aka AGPT2, ANG2, LMPHM10}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, 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}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, KRT14 (keratin 14) [NCBI Gene 3861] {aka CK14, EBS1, EBS1A, EBS1B, EBS1C, EBS1D}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** calcification (MESH:D002114), inflammation (MESH:D007249), blood surface coagulation (MESH:D001778), calculus (MESH:D002137), LLLI (MESH:D009800), Cytotoxicity (MESH:D064420), pain (MESH:D010146), infection (MESH:D007239), bleeding (MESH:D006470), Palatal Wounds (MESH:D014947)
- **Chemicals:** CO2 (MESH:D002245), ATP (MESH:D000255), lipopolysaccharide (MESH:D008070), tetrazolium salt (MESH:D013778), water (MESH:D014867), butorphanol (MESH:D002077), reactive oxygen species (MESH:D017382), PBS (MESH:D007854), midazolam (MESH:D008874), hydroxyapatite (MESH:D017886), medetomidine (MESH:D020926), CellTiter 96 AQueous One Solution (-), oxygen (MESH:D010100)
- **Species:** Homo sapiens (human, species) [taxon 9606], Porphyromonas gingivalis (species) [taxon 837], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** C800F
- **Cell lines:** HUVEC — Homo sapiens (Human), Finite cell line (CVCL_2959)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13024978/full.md

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Source: https://tomesphere.com/paper/PMC13024978