This study demonstrates that sequential hydrogen-releasing implants significantly enhance soft tissue integration through dual mechanisms: reducing oxidative stress and promoting macrophage polarization during the inflammatory phase, followed by sustained collagen and blood vessel formation during the remodeling phase. By coordinating MAPK signaling activation in fibroblasts and endothelial cells, this hydrogen-based approach addresses a critical limitation in long-term implant success and represents a promising therapeutic strategy for improving implant biocompatibility.
Plain-Language Summary
Researchers developed a dental implant that slowly releases hydrogen gas to improve how well soft tissue (gums and surrounding tissue) integrates with the implant. The implant releases hydrogen in two phases: first, it responds to acidic conditions around the implant to reduce harmful molecules called reactive oxygen species and promote beneficial immune cells; then, it continues releasing hydrogen to support collagen formation and blood vessel growth. The study was conducted in laboratory cell cultures, not in people or animals.
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 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 H2 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 H2 based on the hierarchical nanostructure, effectively promoting collagen fiber formation and angiogenesis. Surprisingly, we propose that H2 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 H2 release kinetics that matches the temporal progression of soft tissue integration, implying great potential of enhancing soft tissue integration.
