Sequential hydrogen-release implant for promoting the soft tissue integration through immunomodulatory and pro-remodeling coupling.

Yuan, Yue; Hou, Zishuo; Chen, Miaomiao; Yu, Jingwei; Zhou, Minghao; Kang, Jiaxin; Wang, Tengjiao; Li, Peng et al. · Bioact Mater · 2026

basic_science · Level V

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Abstract

The weaker soft tissue integration around implants compared to natural teeth poses a substantial challenge to the long-term success of implants. To enhance soft tissue integration, we develop an on-demand and long-lasting H<sub>2</sub>-releasing implant to achieve precise sequential regulation of the soft tissue integration through immunomodulation and pro-remodeling coupling. In the inflammatory phase, the system on-demand releases H<sub>2</sub> responded to the local mild acidic microenvironment, which eliminates 73.6 % reactive oxygen species to induce M2 macrophage polarization, thereby establishing a pro-remodeling microenvironment. During the subsequent remodeling phase, the implant sustains release H<sub>2</sub> based on the hierarchical nanostructure, effectively promoting collagen fiber formation and angiogenesis. Surprisingly, we propose that H<sub>2</sub> can coordinately activate MAPK signaling in both gingival fibroblasts and vascular endothelial cells, coupled with stimulating pro-angiogenic paracrine of gingival fibroblasts. This implant achieves the on-demand transition of H<sub>2</sub> release kinetics that matches the temporal progression of soft tissue integration, implying great potential of enhancing soft tissue integration.