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

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.

Study details

Article type

Original Research

Disease / injury model

Dental implant model (peri-implant soft tissue integration)

Duration

28 days

Dose comparison

No direct comparison of different hydrogen doses or concentrations; focus is on the presence or absence of hydrogen release.

Dose-dependent effect

No

Outcome

Positive

Findings

The study demonstrates that a sequential hydrogen-releasing titanium implant enhances soft tissue integration (STI) around dental implants by modulating both the inflammatory and remodeling phases. The implant releases H2 on-demand in response to local pH, scavenging ROS, promoting M2 macrophage polarization, and subsequently enhancing collagen fiber formation and angiogenesis via MAPK pathway activation in gingival fibroblasts and endothelial cells. In vivo and in vitro results show improved STI, reduced inflammation, and increased tissue remodeling.