Yue Sun

Macrophage polarization toward M1 phenotype (pro-inflammation) is closely associated with the destructive phase of periodontal inflammation. Nanoceria is verified to inhibit M1 polarization of macrophages by the favorable ability of reactive oxygen species (ROS) scavenging. However, the function of nanoceria on macrophage polarization toward M2 phenotype (anti-inflammation) in reparative phase of periodontal inflammation is quite limited. In this work, by introducing an antioxidant drug quercetin onto nano-octahedral ceria, synergistic and intense regulation of host immunity against periodontal disease is realized. Such nanocomposite can control the phenotypic switch of macrophages by not only inhibition of M1 polarization for suppressing the damage in the destructive phase but also promotion of M2 polarization for regenerating the surrounding tissues in reparative phase of periodontal disease. As-prepared nanocomposite can effectively increase the M2/M1 ratio of macrophage polarization in inflammatory cellular models by lipopolysaccharide stimulation. More importantly, the nanocomposite also exerts an improved therapeutic potential against local inflammation by significant downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines in an animal model with periodontal inflammation. Therefore, this newly developed nanomedicine is efficient in ROS scavenging and driving pro-inflammatory macrophages to the anti-inflammatory phenotype to eliminate inflammation, thereby providing a promising candidate for treating periodontal inflammation.

Abstract Numerous nanomedicines currently emerge to reduce the dramatic threat in antibiotics resistance for antibacterial application against severe bacterial infections, while it is restricted by over‐reacted immune response to pathogenic bacteria. Herein, enzymatic activity is introduced into the zeolitic imidazolate framework‐8 (ZIF‐8) to achieve sterilization by releasing Zn ions, as well as inflammation regulation through the variable valence of Mn ions that are uniformly doped into its framework. Within this simple metal organic framework (MOF) structure design, Mn‐ZIF‐8 possesses the co‐existence of Mn 2+ /Mn 4+ to endow the nanocomposite with the anti‐inflammatory capabilities, which can be adjusted through the redox environment. The enzymatic activity of Mn ions and superiority of pore structure of ZIF‐8 are effectively combined to realize the substrate selection via reactant molecular size and high‐efficiency internal catalytic performance. By such design, this nanocomposite would not only exhibit an excellent antibacterial performance against pathogenic bacteria, but also reshape the inflammatory immunity by regulating macrophage polarization to suppress over‐reacted inflammation, leading to a favorably therapeutic efficiency on bacteria‐infected wound healing in animal models. Taken together, this nanoplatform provides effective approach for accelerating infected wound healing via bacteria killing and inflammation modulation, and may be extended for the therapy of other severe bacteria‐induced infections.

-infected mandible defects of rats with NIR irradiation. GTAM scaffolds could accelerate the healing of infection and bone regeneration, and play synergistic roles in antibacterial and osteogenic effects. This study not only provides a strategy for the precise osteogenesis of infected bone defects, but also broadens the biomedical applications of MXene photothermal materials.