Work

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

Year: 2025

Type: article

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 2 -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 2 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 2 based on the hierarchical nanostructure, effectively promoting collagen fiber formation and angiogenesis. Surprisingly, we propose that H 2 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 2 release kinetics that matches the temporal progression of soft tissue integration, implying great potential of enhancing soft tissue integration. • The established soft tissue integration (STI) has less fiber and vasculature, making it prone to disruption and infection. • The STI process can be broadly categorized into two progressive phases: the inflammatory phase and the remodeling phase. • An innovative H 2 -releasing implant was designed to sequentially regulate STI through immunomodulation and pro-remodeling. • H 2 can activate MAPK signaling for proliferation, coupled with stimulating pro-angiogenic paracrine of gingival fibroblasts.

Source: Bioactive Materials

DOI: 10.1016/j.bioactmat.2025.11.018