Hydrogen Releasing Coating Implant For Temporally Regulating Soft Tissue Integration

This study developed a sequentially Hydrogen gas (H2) releasing coating on titanium surface, and systematically investigated the effects and underlying mechanisms of H2 on soft tissue integration. Mesoporous dopamine nanoparticles were used as carriers for ammonia borane and loaded onto titanium surface treated with microarc oxidation. The surface characterization was systematically tested. In vitro, the effects of H2 on the biological behaviors of gingival fibroblasts, vascular endothelial cells, and macrophages were assessed. In vivo, the soft tissue integration was evaluated in a rat implantation model. The underlying mechanism was explored through transcriptomics analysis and molecular biology experiment. The H2-releasing coating was constructed, and could release H2 in response to pH variations. In vitro and in vivo results indicated that H2 can effectively suppress the excessive production of reactive oxygen species, thereby inducing macrophages to polarize towards the pro-remodeling phenotype. Moreover, it can promote fiber formation and angiogenesis, effectively enhancing soft tissue integration. Mechanistic investigations further elucidated that H2 promoted soft tissue integration via upregulating the MAPK signaling pathway. The H2 release strategy on titanium surface proposed in this study dynamically regulates the formation process of soft tissue integration by response to local microenvironmental pH changes, thereby enhancing tissue integration to improve the long-term success rate of implants.