Chiral Fe<sub>3</sub>O<sub>4</sub>/GelMA hydrogels regulate the osteoimmune microenvironment via Itgb3-mediated macrophage polarization to combat peri-implantitis.

Shi, Diwen; Mu, Xin; Cao, Hongjuan; Hao, Fengyu; Xu, Xiaoqian; Wu, Lin · Bioact Mater · 2026

basic_science · Level V

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Abstract

Peri-implantitis continues to pose a significant clinical challenge due to its complex osteoimmune microenvironment, which evolves through distinct pathological phases characterized by acute infection-driven oxidative stress and chronic immune-bone dysregulation. This stage-specific progression complicates clinical management, necessitating targeted therapeutic strategies. To address this challenge, we developed injectable chiral hydrogels based on gelatin methacryloyl (GelMA) and L/D-cysteine-modified Fe<sub>3</sub>O<sub>4</sub> nanoparticles. Our results show that L-FG promotes M2 macrophage polarization through YTHDF1-m<sup>6</sup>A-<i>Itgb3</i> axis, supporting bone formation during chronic bone resorption phase, while D-FG enhances the peroxidase-like activity of Fe<sub>3</sub>O<sub>4</sub> and activates PI3K/Akt signaling to mitigate oxidative stress in acute inflammation. In the rat peri-implantitis model, both hydrogels significantly enhanced bone regeneration, with L-FG elevating M2 macrophage infiltration and YTHDF1/CD61 co-expression. This study presents a stage-adaptive chiral hydrogel system that separately addresses oxidative stress in acute phases and immunomodulation in chronic phases, providing a therapeutic strategy for peri-implantitis.