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

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 H2-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 H2responded 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 H2based on the hierarchical nanostructure, effectively promoting collagen fiber formation and angiogenesis. Surprisingly, we propose that H2can 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 H2release kinetics that matches the temporal progression of soft tissue integration, implying great potential of enhancing soft tissue integration.Image 1View The PDF