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Clinically, it is difficult to endow implants with excellent osteogenic ability and antibacterial activity simultaneously. Herein, the self-activating implants modified with hydroxyapatite (HA)/MoS2 coating are designed to prevent Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) infections and accelerate bone regeneration simultaneously. The electron transfer between bacteria and HA/MoS2 is triggered when bacteria contacted with the material. RNA sequencing data reveals that the expression level of anaerobic respiration–related genes is up-regulated and the expression level of aerobic respiration–related genes is down-regulated when bacteria adhere to the implants. HA/MoS2 presents a highly effective antibacterial efficacy against both S. aureus and E. coli because of bacterial respiration–activated metabolic pathway changes. Meanwhile, this coating promotes the osteoblastic differentiation of mesenchymal stem cells by altering the potentials of cell membrane and mitochondrial membrane. The proposed strategy exhibits great potential to endow implants with self-activating anti-infection performance and osteogenic ability simultaneously.

Preventing multidrug-resistant bacteria-related infection and simultaneously improving osseointegration are in great demand for orthopedic implants. However, current strategies are still limited to a combination of non-U.S. Food and Drug Administration-approved antibacterial and osteogenic agents. Here, we develop a food-grade probiotic-modified implant to prevent methicillin-resistant Staphylococcus aureus (MRSA) infection and accelerate bone integration. Lactobacillus casei is cultured on the surface of alkali heat-treated titanium (Ti) substrates and inactivated by ultraviolet irradiation to avoid sepsis induced by viable bacteria. This inactivated L. casei biofilm shows excellent 99.98% antibacterial effectiveness against MRSA due to the production of lactic acid and bacteriocin. In addition, the polysaccharides in the L. casei biofilm stimulate macrophages to secrete abundant osteogenic cytokines such as oncostatin M and improve osseointegration of the Ti implant. Inactivated probiotics modification can be a promising strategy to endow implants with both excellent self-antibacterial activity and osteointegration ability.

Preventing deep bacterial infection and simultaneously enhancing osteogenic differentiation are in great demand for osteomyelitis. Microwave (MW) dynamic therapy is attracting attention due to its excellent penetration ability, but the mechanism of MW‐induced reactive oxygen species (ROS) is still unknown. Herein, MW‐responsive engineered pseudo‐macrophages (M‐Fe3O4/Au nanoparticles (NPs)) are fabricated to clear Staphylococcus aureus infections and induce M2 polarization of macrophages to improve osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) under MW irradiation. Fe3O4/Au NPs can generate ·O2− and heat under MW irradiation in a saline solution, and the mechanism is put forward via finite element modeling and density functional theory calculations. Due to the gap plasmon, electromagnetic hotspots are produced at Fe3O4–Au interface at 2.45 GHz. Because of these induced electromagnetic hotspots, the sodium species is field‐ionized and subsequently reacts with oxygen to produce ·O2−. Meanwhile, the Fe3O4/Au NPs have a stronger ability than Fe3O4 NPs to fix oxygen, favoring the production of ROS. Additionally, MW‐treated macrophages diminish to secrete inflammatory cytokines, resulting in the decrease of ROS production in MSCs and thus enhancing their osteogenic differentiation. These engineered pseudo‐macrophages will be promising for effectively treating bacterial infections and promoting osteoblast differentiation simultaneously in deep tissues under MW irradiation.

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Using noninvasive stimulation of cells to control cell fate and improve bone regeneration by optical stimulation can achieve the aim of precisely orchestrating biological activities. In this study, we create a fast and repeatable photoelectric-responsive microenvironment around an implant using a bismuth sulfide/hydroxyapatite (BS/HAp) film. The unexpected increase of photocurrent on the BS/HAp film under near-infrared (NIR) light is mainly due to the depletion of holes through PO 4 3− from HAp and interfacial charge transfer by HAp compared with BS. The electrons activate the Na + channel of mesenchymal stem cells (MSCs) and change the cell adhesion in the intermediate environment. The behavior of MSCs is tuned by changing the photoelectronic microenvironment. RNA sequencing reveals that when photoelectrons transfer to the cell membrane, sodium ions flux and the membrane potential depolarizes to change the cell shape. Meanwhile, calcium ions fluxed and FDE1 was upregulated. Furthermore, the TCF/LEF in the cell nucleus began transcription to regulate the downstream genes involved in osteogenic differentiation, which is performed through the Wnt/Ca 2+ signaling pathway. This research has created a biological therapeutic strategy, which can achieve in vitro remotely, precisely, and noninvasively controlling cell differentiation behaviors by tuning the in vivo photoelectric microenvironment using NIR light.