# Sequential hydrogen-release implant for promoting the soft tissue integration through immunomodulatory and pro-remodeling coupling.
> 段階的水素放出インプラントによる免疫調節とリモデリング促進の連携を通じた軟組織統合の向上


## Abstract

Insufficient soft tissue integration around dental implants remains a major obstacle to long-term implant success. This study describes an implant engineered to release molecular hydrogen (H2) in a demand-responsive and sustained manner, temporally matched to the two principal phases of soft tissue healing. During the inflammatory phase, H2 is liberated in response to the mildly acidic local microenvironment, scavenging 73.6% of reactive oxygen species and driving macrophage polarization toward the M2 phenotype, thereby establishing conditions favorable for tissue remodeling. In the subsequent remodeling phase, a hierarchical nanostructure enables continued H2 release that promotes collagen fiber deposition and angiogenesis. Mechanistically, H2 was found to activate MAPK signaling concurrently in gingival fibroblasts and vascular endothelial cells, while also stimulating pro-angiogenic paracrine secretion from fibroblasts. The on-demand kinetic switching of H2 release aligns with the temporal dynamics of soft tissue integration, suggesting strong potential for improving peri-implant outcomes.

### Mechanism

H2 released in response to mild acidity scavenges ROS and induces M2 macrophage polarization; sustained H2 then activates MAPK signaling in gingival fibroblasts and endothelial cells and stimulates pro-angiogenic paracrine secretion, collectively promoting collagen formation and angiogenesis.

## Bibliographic

- **Authors**: Yuan Y, Hou Z, Chen M, Yu J, Zhou M, Kang J, et al.
- **Journal**: Bioact Mater
- **Year**: 2026
- **PMID**: [41334374](https://pubmed.ncbi.nlm.nih.gov/41334374/)
- **DOI**: [10.1016/j.bioactmat.2025.11.018](https://doi.org/10.1016/j.bioactmat.2025.11.018)
- **PMC**: [PMC12666708](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12666708/)
- **Study type**: in vitro study
- **Delivery route**: in vitro
- **Effect reported**: positive

## Delivery context

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

## Safety notes

This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 41334374. https://h2-papers.org/en/papers/41334374
> **Source**: PubMed PMID [41334374](https://pubmed.ncbi.nlm.nih.gov/41334374/)