Periodontitis is an inflammatory disease initiated by bacterial infection, developed by excessive immune response, and aggravated by high level of reactive oxygen species (ROS). Hence, herein, a versatile metal-organic framework (MOF)-based nanoplatform is prepared using mesoporous Prussian blue (MPB) nanoparticles to load BA, denoted as MPB-BA. The established MPB-BA nanoplatform serves as a shelter and reservoir for vulnerable immunomodulatory drug BA, which possesses antioxidant, anti-inflammatory and anti-bacterial effects. Thus, MPB-BA can exert its antioxidant, anti-inflammatory functions through scavenging intracellular ROS to switch macrophages from M1 to M2 phenotype so as to relieve inflammation. The underlying molecular mechanism lies in the upregulation of phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2) to scavenge ROS and subsequently inhibit the nuclear factor kappa-B (NF-κB) signal pathway. Moreover, MPB-BA also exhibited efficient photothermal antibacterial activity against periodontal pathogens under near-infrared (NIR) light irradiation. In vivo RNA sequencing results revealed the high involvement of both antioxidant and anti-inflammatory pathways after MPB-BA application. Meanwhile, micro-CT and immunohistochemical staining of p-Nrf2 and p-P65 further confirmed the superior therapeutic effects of MPB-BA than minocycline hydrochloride. This work may provide an insight into the treatment of periodontitis by regulating Nrf2/NF-κB signaling pathway through photothermal bioplatform-assisted immunotherapy.

Purpose: Zinc (Zn), an essential trace element in the body, has stable chemical properties, excellent osteogenic ability and moderate immunomodulatory property. In the present study, a Zn-incorporated TiO₂ nanotube (TNT) was fabricated on titanium (Ti) implant material. We aimed to evaluate the influence of nano-scale topography and Zn on behaviors of murine RAW 264.7 macrophages. Moreover, the effects of Zn-incorporated TNT surface-regulated macrophages on the behaviors and osteogenic differentiation of murine MC3T3-E1 osteoblasts were also investigated. Methods: TNT coatings were firstly fabricated on a pure Ti surface using anodic oxidation, and then nano-scale Zn particles were incorporated onto TNTs by the hydrothermal method. Surface topography, chemical composition, roughness, hydrophilicity, Zn release pattern and protein adsorption ability of the Zn-incorporated TiO₂ nanotube surface were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), surface profiler, contact angle test, Zn release test and protein adsorption test. The cell behaviors and both pro-inflammatory (M1) and pro-regenerative (M2) marker gene and protein levels in macrophages cultured on Zn-incorporated TNTs surfaces with different TNT diameters were detected. The supernatants of macrophages were extracted and preserved as conditioned medium (CM). Furthermore, the behaviors and osteogenic properties of osteoblasts cultured in CM on various surfaces were evaluated. Results: The release profile of Zn on Zn-incorporated TNT surfaces revealed a controlled release pattern. Macrophages cultured on Zn-incorporated TNT surfaces displayed enhanced gene and protein expression of M2 markers, and M1 markers were moderately inhibited, compared with the LPS group (the inflammation model). When cultured in CM, osteoblasts cultured on Zn-incorporated TNTs showed strengthened cell proliferation, adhesion, osteogenesis-related gene expression, alkaline phosphatase activity and extracellular mineralization, compared with their TNT counterparts and the Ti group. Conclusion: This study suggests that the application of Zn-incorporated TNT surfaces may establish an osteogenic microenvironment and accelerate bone formation. It provided a promising strategy of Ti surface modification for a better applicable prospect.

To improve initial osteoblast adhesion and subsequent osseointegration, TiO2 nanotubes layer was constructed on the titanium (Ti) surface by anodic oxidation (AO), with an additional hydroxyapatite (HA) coating to form the AO/HA surface. Tests on in vitro cellular activity displayed that the AO surface, especially the AO/HA surface, promoted initial adhesion, proliferation and differentiation of osteoblast cells. The modified AO and AO/HA surfaces further presented an up-regulated gene expression of osteogenic and adhesion markers collagen type 1 (COL), osteopontin (OPN), osteocalcin (OCN) and vinculin. In addition, in vivo experiments with a rat model demonstrated that the AO surface, particularly the AO/HA surface, achieved earlier osseointegration and a superior bone bonding ability compared with Ti. Our study shed light on a synergistic role played by nanotopography and HA in promoting osteoblast adhesion, proliferation, differentiation and osseointegration, thus suggesting a promising method for better modifying the implant surface.

A hierarchical hybrid micro/nanostructure was produced on the surface of titanium (Ti) implants by combined use of acid etching and anodic oxidation. The bioactivity of the modified Ti was evaluated by a simulated body fluid (SBF) soaking test and in vitro cell culture experiments. The results showed that the surface-modified Ti implants had a microstructure with enhanced surface roughness. There was also a nanostructure superimposed on the microstructure, forming a hierarchical hybrid micro/nanostructure. The modified Ti accelerated the Ca–P mineralization deposition on their surface in SBF, and promoted osteoblast adhesion, proliferation, and bone-related gene expression compared to the polished Ti and the Ti implants subjected only to acid etching or anodic oxidation, which was ascribed to the synergistic effects of both micro- and nanotopography generated. This study provides a simple and cost-effective approach to enhance the bioactivity and biocompatibility of orthopaedic implants, and points out the importance of both micro and nanotopography.