Glucose-primed PEEK orthopedic implants for antibacterial therapy and safeguarding diabetic osseointegration.

Diabetic infectious microenvironment (DIME) frequently leads to a critical failure of osseointegration by virtue of its main peculiarities including typical hyperglycemia and pathogenic infection around implants. To address the plaguing issue, we devise a glucose-primed orthopedic implant composed of polyetheretherketone (PEEK), Cu-chelated metal-polyphenol network (hauberk coating) and glucose oxidase (GOx) for boosting diabetic osseointegration. Upon DIME, GOx on implants sostenuto consumes glucose to generate H2O2, and Cu liberated from hauberk coating catalyzes the H2O2 to highly germicidal •OH, which massacres pathogenic bacteria through photo-augmented chemodynamic therapy. Intriguingly, the catalytic efficiency of the coating gets greatly improved with the turnover number (TON) of 0.284 s-1. Moreover, the engineered implants exhibit satisfactory cytocompatibility and facilitate osteogenicity due to the presence of Cu and osteopromotive polydopamine coating. RNA-seq analysis reveals that the implants enable to combat infections and suppress pro-inflammatory phenotype (M1). Besides, in vivo evaluations utilizing infected diabetic rat bone defect models at week 4 and 8 authenticate that the engineered implants considerably elevate osseointegration through pathogen elimination, inflammation dampening and osteogenesis promotion. Altogether, our present study puts forward a conceptually new tactic that arms orthopedic implants with glucose-primed antibacterial and osteogenic capacities for intractable diabetic osseointegration.

Rapid sterilisation and diabetic cutaneous regeneration using cascade bio-heterojunctions through glucose oxidase-primed therapy.

The cutaneous wound in diabetic patients frequently encounters intractable pathogenic infections due to the hyperglycemia micromilieu which is conducive to bacterial growth and multiplication. Despite the extensive clinical use of antibiotics to treat bacterial infections, the emergence of drug-resistant and super pathogens as well as the potential side effects of antibiotics have elicited alarming challenges to public health. To address this daunting concern, we devise and develop a photo-activated cascade bio-heterojunctions (C-bio-HJs) for rapid sterilization and diabetic cutaneous regeneration. In the designed C-bio-HJs, photo-generated electron-hole pairs of graphite-phase carbon nitride (g-C3N4) are effectively separated with the marriage of molybdenum disulfide (MoS2), which achieves the augmented photodynamic antibacterial effect. Moreover, glucose oxidase (GOx) tethered on the bio-HJs catalyzes glucose into hydrogen peroxide (H2O2) in diabetic wounds for starvation therapy. Furthermore, Mo4+ enables the catalysis of H2O2 into a highly effective hydroxyl radical (·OH) for chemodynamic-photothermal combined antibacterial therapy. Both in vitro and in vivo results authenticate the cascading antibacterial properties and skin regeneration-promoting effects of the C-bio-HJs, which provide a facile strategy to combat diabetic wound healing through the synergistic GOx-primed dynamic therapies.

COVID-19 vaccine uptake, reasons, and associated factors among older adults in Shenzhen, China.

Evidence is limited on the actual uptake of the coronavirus disease 2019 (COVID-19) vaccine among older adults, especially those with chronic diseases, during the pandemic. To examine COVID-19 vaccine uptake, reasons, and associated factor among older adults, a cross-sectional survey was conducted between September 24 and October 20, 2021 among older adults aged 60 and above in Shenzhen, China. Logistic regression analysis was used to examine associations of COVID-19 vaccine uptake with sociodemographic characteristics, pneumonia vaccination history, and participation in health education activities among older adults and among those with chronic diseases. Of the 951 participants, 82.8% reported being vaccinated against COVID-19 during the study period, but this proportion was relatively lower among adults aged 80 and above (62.7%) and those with chronic diseases (77.9%). The top-rated reasons for not being vaccinated included doctors not recommending it due to underlying diseases (34.1%), not being ready for it (18.3%), and failure to make an appointment (9.1%). General older adults who were aged below 70, had a high school and above education, were permanent residents of Shenzhen, were with good health and had pneumonia vaccination history were more likely to take the COVID-19 vaccination. Yet, among older adults with chronic diseases, other than age and permanent residency status, health status was the only significant indicator of COVID-19 vaccine uptake. Our study added to evidence that health condition is the critical barrier to the actual uptake of the COVID-19 vaccine among Chinese older adults, especially those aged 80 and above and those with chronic diseases.

Bioheterojunction-Engineered Polyetheretherketone Implants With Diabetic Infectious Micromilieu Twin-Engine Powered Disinfection for Boosted Osteogenicity.

Diabetic infectious micromilieu (DIM) leads to a critical failure rate of osseointegration by virtue of two main peculiarities: high levels of topical glucose and inevitable infection. To tackle the daunting issue, a bioheterojunction-engineered orthopedic polyetheretherketone (PEEK) implant consisting of copper sulfide/graphene oxide (CuS/GO) bioheterojunctions (bioHJs) and glucose oxidase (GOx) is conceived and developed for DIM enhanced disinfection and boosted osseointegration. Under hyperglycemic micromilieu, GOx can convert surrounding glucose into hydrogen peroxide (H2 O2 ). Then, upon infectious micromilieu, the bioHJs enable the catalyzation of H2 O2 to highly germicidal hydroxyl radical (·OH). As a result, the engineered implants massacre pathogenic bacteria through DIM twin-engine powered photo-chemodynamic therapy in vitro and in vivo. In addition, the engineered implants considerably facilitate cell viability and osteogenic activity of osteoblasts under a hyperglycemic microenvironment via synergistic induction of copper ions (Cu2+ ) and GO. In vivo studies using bone defect models of diabetic rats at 4 and 8 weeks further authenticate that bioHJ-engineering PEEK implants substantially elevate their osseointegration through biofilm elimination and vascularization, as well as macrophage reprogramming. Altogether, the present study puts forward a tactic that arms orthopedic implants with DIM twin-engine powered antibacterial and formidable osteogenic capacities for diabetic stalled osseointegration.

Heterostructured Metal-Organic Frameworks/Polydopamine Coating Endows Polyetheretherketone Implants with Multimodal Osteogenicity and Photoswitchable Disinfection.

Clinically, bacteria-induced contagion and insufficient osseointegrative property inevitably elicit the failure of orthopedic implants. Herein, a heterostructured coating consisting of simvastatin (SIM)-laden metal-organic frameworks and polydopamine nanolayers is created on a porous bioinert polyetheretherketone implant. The heterostructured coating significantly promotes cytocompatibility and osteogenic differentiation through multimodal osteogenicity mechanisms of zinc ion (Zn2+ ) therapy, SIM drug therapy, and surface micro-/nano-topological stimulation. Under the illumination of near-infrared (NIR) light, singlet oxygen (1 O2 ) and local hyperthermia are produced; besides, NIR light dramatically accelerates the release of Zn2+ ions from heterostructured coatings. Gram-positive and -negative bacteria are effectively eradicated by the synergy of photothermal/photodynamic effects and photo-induced accelerated delivery of Zn2+ ions. The superior osteogenicity and osseointegration, as well as photoswitchable disinfection controlled by NIR light are corroborated via in vivo results. This work highlights the great potential of photoresponsive heterostructured orthopedic implants in treatment of the noninvasive bone reconstruction of bacteria-associated infectious tissues through multimodal phototherapy and photoswitchable ion-therapy.

Multi-activity cobalt ferrite/MXene nanoenzymes for drug-free phototherapy in bacterial infection treatment.

Drug-free antibacterial strategies are of great significance for pathogenic bacterial infection treatment in clinical practice. Phototherapy with antibacterial function plays a vital role in mainstream germicidal research. However, phototherapy could lead to residual heat and excess reactive oxygen species (ROS), which are the main side-effects during antibacterial treatment. Unique CoFe2O4/MXene (CM) nanoenzymes, which were fabricated with electrostatic interactions, have been designed to conquer those challenges caused by side-effects of phototherapy in our research. The CM nanoenzymes possess many promising properties including photothermal and photodynamic induced phototherapy and mimic peroxidase (POD), glutathione oxidase (GSHOx), and catalase (CAT). Upon treatment with near-infrared (NIR) light, CM nanoenzymes can create a local high-temperature circumstance as well as raise bacterial membrane permeability. Furthermore, the photodynamic process and multi-enzyme-mimicking activities of CM enzymes boost the interbacterial ROS level. Herein, bacteria can hardly survive in synergistic phototherapy and multi-enzyme-mimicking catalytic therapy in vitro and in vivo. Meanwhile, the CM nanoenzymes exhibit excellent biocompatibility in vitro and in vivo. Overall, this research establishes a strong foundation for effectively employing nanoenzymes, leading to a new way to cure bacterial infections.

Dual Ag/ZnO-Decorated Micro-/Nanoporous Sulfonated Polyetheretherketone with Superior Antibacterial Capability and Biocompatibility via Layer-by-Layer Self-Assembly Strategy.

Polyetheretherketone is attractive for dental and orthopedic applications due to its mechanical attributes close to that of human bone; however, the lack of antibacterial capability and bioactivity of polyetheretherketone has substantially impeded its clinical applications. Here, a dual therapy implant coating is developed on the 3D micro-/nanoporous sulfonated polyetheretherketone via layer-by-layer self-assembly of Ag ions and Zn ions. Material characterization studies have indicated that nanoparticles consisting of elemental Ag and ZnO are uniformly incorporated on the porous sulfonated polyetheretherketone surface. The antibacterial assays demonstrate that Ag-decorated sulfonated polyetheretherketone and Ag/ZnO-codecorated sulfonated polyetheretherketone effectively inhibit the reproduction of Gram-negative and Gram-positive bacteria. Owing to the coordination of micro-/nanoscale topological cues and Zn induction, the Ag/ZnO-codecorated sulfonated polyetheretherketone substrates are found to enhance biocompatibility (cell viability, spreading, and proliferation), and hasten osteodifferentiation and -maturation (alkaline phosphate activity (ALP) production, and osteogenesis-related genetic expression), compared with the Ag-decorated sulfonated polyetheretherketone and the ZnO-decorated sulfonated polyetheretherketone counterparts. The dual therapy Ag/ZnO-codecorated sulfonated polyetheretherketone has an appealing bacteriostatic performance and osteogenic differentiation potential, showing great potential for dental and orthopedic implants.

Graphene-Oxide-Decorated Microporous Polyetheretherketone with Superior Antibacterial Capability and In Vitro Osteogenesis for Orthopedic Implant.

Due to its similar elastic modulus of human bones, polyetheretherketone (PEEK) has been considered as an excellent cytocompatible material. However, the bioinertness, poor osteoconduction, and weak antibacterial activity of PEEK limit its wide applications in clinics. In this study, a facile strategy is developed to prepare graphene oxide (GO) modified sulfonated polyetheretherketone (SPEEK) (GO-SPEEK) through a simple dip-coating method. After detailed characterization, it is found that the GO closely deposits on the surface of PEEK, which is attributed to the π-π stacking interaction between PEEK and GO. Antibacterial tests reveal that the GO-SPEEK exhibits excellent suppression toward Escherichia coli. In vitro cell attachment, growth, differentiation, alkaline phosphatase activity, quantitative real-time polymerase chain reaction analyses, and calcium mineral deposition all illustrate that the GO-SPEEK substrate can significantly accelerate the proliferation and osteogenic differentiation of osteoblast-like MG-63 cells compared with those on PEEK and SPEEK groups. These results suggest that the GO-SPEEK has an improved antibacterial activity and cytocompatibility in vitro, showing that the developed GO-SPEEK has a great potential as the bioactive implant material in bone tissue engineering.

Enhanced antibacterial property and osteo-differentiation activity on plasma treated porous polyetheretherketone with hierarchical micro/nano-topography.

Implantable polyetheretherketone (PEEK) has great biomedical potential as hard tissue substitute in orthopedic application due to its outstanding mechanical properties and excellent biological stability. However, the poor osseointegration and bacteriostatic ability of implantable PEEK become the major barrier for its wide clinic application. In this study, a hierarchically micro/nano-topographic PEEK with specific functional groups (amino and COOH/COOR) has been fabricated using facile sulfonation combined with argon plasma treatment. The new developed hierarchically micro/nano-topographic PEEK have enhanced hydrophilicity, surface roughness, as well as the high ability of apatite-layer forming. Antibacterial assessment shows that as-treated samples exhibit better antibacterial activity. The cellular responses in osteoblast-like MG-63 cells culturing experiment reveal that the micro/nano-topography accompanied with specific functional groups improves the cell adhesion at the initial stage, further ameliorates proliferation and osteogenic differentiation of MG-63. This study proposes a promising approach to increase osteo-differentiation activity and bacteriostasis of PEEK via synergistic effects involving surface topologic structure and chemical modification, which shows great potential in developing advanced implantable materials.