Nanoparticles of Cerium-Doped Zeolitic Imidazolate Framework-8 Promote Soft Tissue Integration by Reprogramming the Metabolic Pathways of Macrophages.

Soft tissue integration around the abutment of implants is the basis of long-term retention of implants. Macrophages are an important component involved in the repair of soft tissue due to their crucial role in improving the biological structure of connective tissues by regulating the fiber synthesis, adhesion, and contraction of gingival fibroblasts. Recent studies have illustrated that cerium-doped zeolitic imidazolate framework-8 (Ce@ZIF-8) nanoparticles (NPs) can attenuate periodontitis via both antibacterial and anti-inflammatory effects. However, the effect of Ce@ZIF-8 NPs on soft tissue integration around the abutment is unknown. Herein, we first prepared Ce@ZIF-8 NPs by a one-pot synthesis. Then, we probed the regulatory effect of Ce@ZIF-8 NPs on macrophage polarization, and further experiments were performed to study the changes of fiber synthesis as well as adhesion and contraction of fibroblasts in the M2 macrophage environment stimulated by Ce@ZIF-8 NPs. Strikingly, Ce@ZIF-8 NPs can be internalized by M1 macrophages through macropinocytosis and caveolae-mediated endocytosis in addition to phagocytosis. By catalyzing hydrogen peroxide to produce oxygen, the mitochondrial function was remedied, while hypoxia inducible factor-1α was restrained. Then, macrophages were shifted from the M1 to M2 phenotype via this metabolic reprogramming pathway, provoking soft tissue integration. These results provide innovative insights into facilitating soft tissue integration around implants.