Introduction: The bone regeneration of endosseous implanted biomaterials is often impaired by the host immune response, especially macrophage-related inflammation which plays an important role in the bone healing process. Thus, it is a promising strategy to design an osteo-immunomodulatory biomaterial to take advantage of the macrophage-related immune response and improve the osseointegration performance of the implant. Methods: In this study, we developed an antibacterial silver nanoparticle-loaded TiO 2 nanotubes (Ag@TiO 2-NTs) using an electrochemical anodization method to make the surface modification and investigated the influences of Ag@TiO 2-NTs on the macrophage polarization, osteo-immune microenvironment as well as its potential molecular mechanisms in vitro and in vivo. Results: The results showed that Ag@TiO 2-NTs with controlled releasing of ultra-low-dose Ag + ions had the excellent ability to induce the macrophage polarization towards the M2 phenotype and create a suitable osteo-immune microenvironment in vitro, via inhibiting PI3K/Akt, suppressing the downstream effector GLUT1, and activating autophagy. Moreover, Ag@TiO 2-NTs surface could improve bone formation, suppress inflammation, and promote osteo-immune microenvironment compared to the TiO 2-NTs and polished Ti surfaces in vivo. These findings suggested that Ag@TiO 2-NTs with controlled releasing of ultra-low-dose Ag + ions could not only inhibit the inflammation process but also promote the bone healing by inducing healing-associated M2 polarization. Discussion: Using this surface modification strategy to modulate the macrophage-related immune response, rather than prevent the host response, maybe a promising strategy for implant surgeries in the future.

Background: Titanium (Ti) implant-associated infection, which is mostly caused by bacterial adhesion and biofilm formation, may result in implant failure and secondary surgery. Thus it is an urgent issue to prevent bacterial infections at the earliest step. Purpose: To develop a novel surface strategy of polydopamine (PDA) and silver (Ag) nanoparticle-loaded TiO 2 nanorods (NRDs) coatings on Ti alloy. Materials and methods: Ag-TiO 2 @PDA NRDs was fabricated on Ti alloy by hydrothermal synthesis. The antibacterial activity of Ag-TiO 2 @PDA NRDs against Escherichia coli and methicillin-resistant Staphylococcus aureus were tested by FE-SEM, Live/Dead staining, zone of inhibition, bacteria counting method and protein leakage analysis in vitro . In addition, an implant infection model was conducted and the samples were tested by X-ray, Micro-CT and histological analysis in vivo . Besides, cell morphology and cytotoxicity of Mouse calvarial cells (MC3T3-E1) were characterized by FE-SEM, immunofluorescence and CCK-8 test in vitro . Results: Our study successfully developed a new surface coating of Ag-TiO 2 @PDA NRDs. The selective physical puncture of bacteria and controlled release of Ag+ ions of Ag-TiO 2 @PDA NRDs achieved a long-lasting bactericidal ability and anti-biofilm activity with satisfied biocompatibility. Conclusion: This strategy may be promising for clinical applications to reduce the occurrence of infection in the implant surgeries

Cigarette smoking (CS) is one of the main factors related to avoidable diseases and death across the world. Cigarette smoke consists of numerous toxic compounds that contribute to the development of osteoporosis and fracture nonunion. Exposure to pulsed electromagnetic fields (PEMF) was proven to be a safe and effective therapy to support bone fracture healing. The aims of this study were to investigate if extremely low frequency (ELF-) PEMFs may be beneficial to treat CS-related bone disease, and which effect the duration of the exposure has. In this study, immortalized human mesenchymal stem cells (SCP-1 cells) impaired by 5% cigarette smoke extract (CSE) were exposed to ELF-PEMFs (16 Hz) with daily exposure ranging from 7 min to 90 min. Cell viability, adhesion, and spreading were evaluated by Sulforhodamine B, Calcein-AM staining, and Phalloidin-TRITC/Hoechst 33342 staining. A migration assay kit was used to determine cell migration. Changes in TGF-β signaling were evaluated with an adenoviral Smad2/3 reporter assay, RT-PCR, and Western blot. The structure and distribution of primary cilia were analyzed with immunofluorescent staining. Our data indicate that 30 min daily exposure to a specific ELF-PEMF most effectively promoted cell viability, enhanced cell adhesion and spreading, accelerated migration, and protected TGF-β signaling from CSE-induced harm. In summary, the current results provide evidence that ELF-PEMF can be used to support early bone healing in patients who smoke.

Aim: To create polydopamine (PDA) and Ag nanoparticle-loaded TiO2 nanotubes coating on titanium (Ti) alloy. Materials & methods: TiO2-PDA-Ag coating was fabricated on Ti implants by electrochemical anodization. The in vitro and in vivo bactericidal and antibiofilm activities were tested. Intracellular reactive oxygen species (ROS) and antioxidative capability were measured, and cell proliferation, adhesion and cell morphology were characterized. Results: TiO2-PDA-Ag coating showed satisfactory bactericidal and antibiofilm activities in vitro and in vivo, improved Ag release pattern, evident ROS scavenging properties and enhanced cell adhesion and proliferation. Conclusion: Our study successfully fabricated a PDA and Ag nanoparticle-loaded TiO2 nanotubes coating on Ti alloy. The improved Ag release kinetics and ROS-scavenging properties achieve an optimal balance between antibacterial ability and biocompatibility.