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Extracellular vesicles (EVs) derived from differentiating induced stem cells maintain their original stemness and differentiating trends and possess strong immunoregulatory capability. Biomaterials equipped with EVs are very promising in regenerative medicine. However, surface EV‐decoration on osteoimplants remains a challenge, due to the complexity of traditional molecular conjugations and the fragility of EVs. Here, mussel‐like molecular adhesion is combined with bioorthogonal click conjugation to introduce EVs on titanium (Ti) implants. The biomimetic adhesion and clickable molecular linkage allow mild and stable tethering of pre‐osteogenic mesenchymal stem cell (MSC)‐derived EVs on Ti implants. EV‐decorated implants exhibit significantly enhanced osseointegration on the bone‐implant surface under diabetic conditions, promoting increased expression of osteogenic genes. Modified surfaces impelled phenotypic alterations in macrophage polarization via multi‐pathway regulation, decreasing proinflammatory M1 macrophage formation, which can lead to the promotion of surface osteogenesis. On Ti rods implanted in a diabetic rat model, EV coating inhibited M1macrophages around the prosthesis, resulting in satisfactory long‐term osseointegration. This study offers a new perspective to represent a simple and effective means for surface EV decoration, providing an osteoimmunomodulatory effect to enhance the diabetic osseointegration of implants. [ABSTRACT FROM AUTHOR]

Recurrent bacterial infections, impenetrable microbial biofilms, and irremediable antibiotic resistance are the most perilous threats in orthopedic implant‐associated infections (IAIs). Recently, chemodynamic therapy (CDT) has been considered a promising therapy, while the clinical practices for existing CDT agents are limited by the low therapeutic efficiency in physiological circumstances. Herein, it is demonstrated that silica‐copper nanosheets (Si@Cu NSs) exhibit a combined therapeutic photothermal‐chemodynamic strategy for IAIs treatment with superior capacity and biocompatibility. This unique design endows the nanostructure with enhanced copper‐based Fenton‐like properties via p‐d orbital hybridization by incorporating copper nanoclusters (Cu NCs) on silicene nanosheets (Si NSs) matrix, integrating inherent photothermal performance of Si NSs with specific catalytic anti‐infection of Cu NCs against planktonic bacteria and biofilms both in vitro and in vivo. This study not only reveals the promising bio‐application prospects of 2D nanocatalytic biomaterials but also demonstrates the feasibility of constructing novel CDT agents by orbital hybridization for the catalytic treatment of IAIs. [ABSTRACT FROM AUTHOR]

Robust bacterial metabolism and the immunosuppression on peripheral immune cells cause biofilm‐associated infections (BAIs) extremely refractory to be eradicated via antibiotics alone. Herein, hierarchical mesoporous UiO‐66 metal–organic framework is decorated with selenite, polypyrrole, and macrophage membrane (MM) to develop a biomimetic nanosphere (USPM). Following the recruitment of USPM to the biofilm microenvironment (BME) via the pathogen‐targeting ability derived from MM. The BME‐responsive USPM can precisely release selenite to penetrate the loosened biofilm in synergy with near‐infrared‐induced mild photothermal therapy (mPTT). Selenite can quickly react with reducing substances to generate hydrogen selenide (H2Se) inside the biofilm. H2Se can competitively inhibit bacterial metabolic processes and disrupt biofilm metabolic homeostasis by cascade amplification effects. Furthermore, H2Se inside the biofilm further sensitizes photothermia to exert a precise local photothermal effect. Outside the biofilm, USPM can simultaneously promote the phagocytosis and autophagy of macrophages to kill and decompose the phagocytosed bacteria. Finally, the well‐decomposed bacterial antigens in macrophages can be presented to antigen‐presenting cells to arouse adaptive immune responses and enhance anti‐biofilm effectiveness further. Such powerful mPTT‐enhanced bacterial metabolic disruption and macrophagic autophagy‐promoted adaptive immune activation suggest an alternative therapeutic strategy to cure refractory BAIs. [ABSTRACT FROM AUTHOR]