Collaborative Design of MgO/FeOx Nanosheets on Titanium: Combining Therapy with Regeneration.

The repair of bone defects caused by osteosarcoma resection remains a clinical challenge because of the tumor recurrence and bacterial infection. Combining tumor and bacterial therapy with bone regeneration properties in bone implants is a promising strategy for the treatment of osteosarcoma. Here, a layer of MgO/FeOx nanosheet is constructed on the Ti implant to prevent tumor recurrence and bacterial infection, while simultaneously accelerating bone formation. This MgO/FeOx double metal oxide demonstrates good peroxidase activity to catalyze H2 O2 , which is rich in tumor microenvironment, to form reactive oxygen species (ROS), and shows good photothermal conversion capacity to produce photothermal effect, thus synergistically killing tumor cells and eliminating tumor tissue. In addition, it generates a local alkaline surface microenvironment to inhibit the energy metabolism of bacteria to enhance the photothermal antibacterial effect. Furthermore, benefiting from the generation of a Mg ion-containing alkaline microenvironment, this MgO/FeOx film can promote the osteogenic differentiation of osteoblast and angiogenesis of vascular endothelial cells in vitro as well as accelerated bone formation in vivo. This study proposes a multifunctional platform for integrating tumor and bacterial therapy and bone regeneration, which has good application prospects for the treatment of osteosarcoma.

Mechanical Force Induced Self-Assembly of Chinese Herbal Hydrogel with Synergistic Effects of Antibacterial Activity and Immune Regulation for Wound Healing.

Skin wounds, especially infected chronic wounds, have attracted worldwide attention due to the high prevalence and poor treatment outcomes. Hydrogel dressings with antibacterial ability and immune regulation property are urgently required. Herein, inspired by the grinding treatment of traditional Chinese medicine, mechanical force is introduced to promote the effective molecular collision and accelerate the self-assembly of chitosan (CS) and puerarin (PUE) for fabricating Chinese-herb-based hydrogels. The antibacterial rate of CS@PUE (C@P) hydrogel is more than 95%, and the wound closed rate is twice that of the control group. Interestingly, the rational design of C@P hydrogels with different PUE ratios enables a refined control over hydrogel formation, nanofiber appearance, viscoelastic, physicochemical, and biological properties. The extraordinary antibacterial ability of C@P hydrogels may originate from the nanofiber structure and the improved zeta potential on account of the orientation of amino groups in CS . Thus, the synergistically antibacterial and immune regulation properties of C@P hydrogels kill bacteria and relieve inflammation in the wound bed, ensuring the anti-infection effect, and boosting wound healing. In addition to providing a universal mechanosynthesis of PUE-based hydrogel for wound healing, this finding is expected to increase the attention paid to Chinese herbal medicines in the construction of biomaterials.

Layered Double Hydroxide-Based Micro "Chemical Factory" with Arsenic Processing and Screening Functions on Nitinol for Gallbladder Cancer Treatment.

Gallbladder cancer is a common malignant tumor of the biliary system with a high fatality rate. Nitinol (Ni-Ti) stents, a standard treatment for prolonging patients' lives, are susceptible to reocclusion and cannot inhibit tumor recurrence because they lack antitumor and antibacterial activity. Herein, an arsenic-loaded layered double-hydroxide film is constructed on Ni-Ti, forming a micro "chemical factory." The LDH plays the role of a "processer" which absorbs highly toxic trivalent arsenic (As(III)) and processes it into lowly toxic pentavalent arsenic (As(V)). It also acts as a "quality-inspector," confining As(III) in the interlayer and releasing only As(V) (the finished product) to the outside. This control mechanism minimizes the toxicity during contact with normal tissue. The acidic microenvironment and overexpression of glutathione in tumor tissues not only accelerates the release of arsenic from the platform but also triggers the in situ transformation of arsenic from lowly toxic As(V) to highly toxic As(III), exerting a strong arsenic-mediated antineoplastic effect. Such a microenvironment-responsive "chemical factory" with arsenic processing and screening functions is expected to prevent tumor overgrowth, metastasis, and bacterial infection and provide new insights into the design of Ni-Ti drug-eluting stents for gallbladder cancer treatment.

Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19.

Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their dynamic changes during the treatment, platelet-to-lymphocyte ratio (PLR) were a concern. We sought to describe the platelet feature of these cases. Single-center case series of the 30 hospitalized patients with confirmed coronavirus disease (COVID)-19 in Huizhou municipal central hospital from January 2020 to February 2020 were retrospectively analyzed. Demographic, clinical, blood routine results, other laboratory results, and treatment data were collected and analyzed. Outcomes of severe patients and nonsevere patients were compared. Univariate analysis showed that: age, platelet peaks, and PLR at peak platelet were the influencing factors in severe patients, multivariate analysis showed that the PLR value at peak platelet during treatment was an independent influencing factor in severe patients. The average hospitalization day of patients with platelet peaks during treatment was longer than those without platelet peaks (P < .05). The average age of patients with platelet peaks during treatment was older than those without platelet peaks (P < .05). The patients with significantly elevated platelets during treatment had longer average hospitalization days. And the higher PLR of patients during treatment had longer average hospitalization days. Single-center case series of the 30 hospitalized patients with confirmed COVID-19 in Huizhou Municipal Central Hospital, presumed that the number of platelets and their dynamic changes during the treatment may have a suggestion on the severity and prognosis of the disease. The patient with markedly elevated platelets and longer average hospitalization days may be related to the cytokine storm. The PLR of patients means the degree of cytokine storm, which might provide a new indicator in the monitoring in patients with COVID-19.

Nanostructural Surfaces with Different Elastic Moduli Regulate the Immune Response by Stretching Macrophages.

A proper immune response is key for the successful implantation of biomaterials, and designing and fabricating biomaterials to regulate immune responses is the future trend. In this work, three different nanostructures were constructed on the surface of titanium using a hydrothermal method, and through a series of in vitro and in vivo experiments, we found that the aspect ratio of nanostructures can affect the elastic modulus of a material surface and further regulate immune cell behaviors. This work demonstrates that nanostructures with a higher aspect ratio can endow a material surface with a lower elastic modulus, which was confirmed by experiments and theoretical analyses. The deflection of nanostructures under the cell adsorption force is a substantial factor in stretching macrophages to enhance cell adhesion and spreading, further inducing macrophage polarization toward the M1 phenotype and leading to intense immune responses. In contrast, a nanostructure with a lower aspect ratio on a material surface leads to a higher surface elastic modulus, making deflection of the material difficult and creating a surface that is not conducive to macrophage adhesion and spreading, thus reducing the immune response. Moreover, molecular biology experiments indicated that regulation of the immune response by the elastic modulus is primarily related to the NF-κB signaling pathway. These findings suggest that the immune response can be regulated by constructing nanostructural surfaces with the proper elastic modulus through their influence on cell adhesion and spreading, which provides new insights into the surface design of biomaterials.

Achieving stem cell imaging and osteogenic differentiation by using nitrogen doped graphene quantum dots.

Nitrogen doped graphene quantum dots (N-GQDs) were synthesized to explore and extend their potential applications in biomedical field. The hemocompatibility and cytotoxity of the obtained N-GQDs were primarily assessed at concentrations ranging from 10 to 100 µg/ml. From the results, it was found that the proliferation of rat Bone Mesenchymal Stem Cells (rBMSCs) was depressed to a certain extent after incubating with the high concentration (100 µg/ml) of N-GQDs. The nanoscale size and superior dispersibility endow N-GQDs with good cell permeability. Meanwhile, owing to their intrinsic photoluminescence characteristic, the N-GQDs can be used to label cells with high uniformity and light stability in absence of chemical dyes. More importantly, the up-regulated expression of alkaline phosphate (ALP), extracellular matrix, osteopontin (OPN) and osteocalcin (OCN) in rBMSCs cultured with N-GQDs, indicating N-GQDs have the abilities to promote rBMSCs osteogenic differentiation. This work would help give a new insight into the advantages of N-GQDs and pave the way for application of N-GQDs in regenerative medicine fields.

Peroxidase-Like Activity of Ethylene Diamine Tetraacetic Acid and Its Application for Ultrasensitive Detection of Tumor Biomarkers and Circular Tumor Cells.

Ethylene diamine tetraacetic acid (EDTA) is such a powerful chelating agent that it may form stable complexes with most metal ions, which has wide applications in industry, agriculture, environment, and pharmaceutical technology. Recently, EDTA was found to enhance the photocatalytic property of some materials. Inspired by this fact of EDTA in the photocatalytic role, we further investigated the photocatalytic property of EDTA and found much the same as that of natural horseradish peroxidase (HRP). This significant discovery of peroxidase-like property may extend the applications of conventional EDTA in life science. A novel and colorimetric sensor based on the peroxidase-like EDTA and unique gold nanorods (GNRs) was designed. Under light irradiation, EDTA may catalyze decomposition of hydrogen peroxide and in situ regulate the longitudinal plasmon wavelength (LPW) of GNRs, displaying various color solution as a read-out means. This colorimetric nanosensor has a great potential to develop into a platform to quantitatively determine analytes as long as the specific antibodies against them were available. Biomarkers of different diseases, such as breast cancer and prostate cancer, were detected with high accuracy. Moreover, combined with immunomagnetic separation of circulating tumor cells (CTCs) from blood, a visual read-out for detection of CTCs was established, which has promising applications in clinical diagnosis, environmental monitoring, and food quality control only using naked eyes.

Silicon-Doped Titanium Dioxide Nanotubes Promoted Bone Formation on Titanium Implants.

While titanium (Ti) implants have been extensively used in orthopaedic and dental applications, the intrinsic bioinertness of untreated Ti surface usually results in insufficient osseointegration irrespective of the excellent biocompatibility and mechanical properties of it. In this study, we prepared surface modified Ti substrates in which silicon (Si) was doped into the titanium dioxide (TiO2) nanotubes on Ti surface using plasma immersion ion implantation (PIII) technology. Compared to TiO2 nanotubes and Ti alone, Si-doped TiO2 nanotubes significantly enhanced the expression of genes related to osteogenic differentiation, including Col-I, ALP, Runx2, OCN, and OPN, in mouse pre-osteoblastic MC3T3-E1 cells and deposition of mineral matrix. In vivo, the pull-out mechanical tests after two weeks of implantation in rat femur showed that Si-doped TiO2 nanotubes improved implant fixation strength by 18% and 54% compared to TiO2-NT and Ti implants, respectively. Together, findings from this study indicate that Si-doped TiO2 nanotubes promoted the osteogenic differentiation of osteoblastic cells and improved bone-Ti integration. Therefore, they may have considerable potential for the bioactive surface modification of Ti implants.

Vacuum extraction enhances rhPDGF-BB immobilization on nanotubes to improve implant osseointegration in ovariectomized rats.

Nanotube morphology has been previously applied to improve osseointegration in osteoporosis, but the osteogenic capability of the technique requires further improvements. This study aimed to investigate the effects of vacuum extraction on the loading of rhPDGF-BB on nanotube arrays as well as its effects on the osseointegration of ovariectomized (OVX) rats. More rhPDGF-BB protein particles aggregated on the nanotube surface and into the nanotube after vacuum extraction for 10 min. The immobilized protein could be slowly released for at least 14 days and still kept its biological activity. In vitro, the immobilized rhPDGF-BB enhanced cell adhesion, proliferation and osteogenic differentiation. In vivo, more rhPDGF-BB immobilized on the nanotube surface also promoted the osseointegration. These results suggest that the enhanced immobilization of rhPDGF-BB on nanotube arrays can potentially be used in the future as an implant surface modification strategy in dental and orthopedic applications in osteoporotic patients. FROM THE CLINICAL EDITOR: This study presents convincing evidence that enhanced immobilization of recombinant human PDGF-BB protein particles on nanotubes lead to improved osteogenic differentiation in an experimental system. When used as a surface modification strategy for dental or orthopedic implants, this method was able to promote osseointegration even in an osteoporotic animal model, raising the likelihood for potential future clinical applications.

A rechargeable coating with temporal-sequence antibacterial activity and soft tissue sealing.

Transcutaneous implants that penetrate through skin or mucosa are susceptible to bacteria invasion and lack proper soft tissue sealing. Traditional antibacterial strategies primarily focus on bacterial eradication, but excessive exposure to bactericidal agents can induce noticeable tissue damage. Herein, a rechargeable model (HPI-Ti) was constructed using perylene polyimide, an aqueous battery material, achieving temporal-sequence regulation of bacterial killing and soft tissue sealing. Charge storage within HPI-Ti is achieved after galvanostatic charge, and chemical discharge is initiated when immersed in physiological environments. During the early discharge stage, post-charging HPI-Ti demonstrates an antibacterial rate of 99.96 ± 0.01 % for 24 h, preventing biofilm formation. Contact-dependent violent electron transfer between bacteria and the material causes bacteria death. In the later discharge stage, the attenuated discharging status creates a gentler electron-transfer micro-environment for fibroblast proliferation. After discharge, the antibacterial activity can be reinstated by recharge against potential reinfection. The antibacterial efficacy and soft tissue compatibility were verified in vivo. These results demonstrate the potential of the charge-transfer-based model in reconciling antibacterial efficacy with tissue compatibility.

Selective Tumor Inhibition Effect of Drug-Free Layered Double Hydroxide-Based Films via Responding to Acidic Microenvironment.

Nickel-titanium alloy stents are widely used in the interventional treatment of various malignant tumors, and it is important to develop nickel-titanium alloy stents with selective cancer-inhibiting and antibacterial functions to avoid malignant obstruction caused by tumor invasion and bacterial colonization. In this work, an acid-responsive layered double hydroxide (LDH) film was constructed on the surface of a nickel-titanium alloy by hydrothermal treatment. The release of nickel ions from the film in the acidic tumor microenvironment induces an intracellular oxidative stress response that leads to cell death. In addition, the specific surface area of LDH nanosheets could be further regulated by heat treatment to modulate the release of nickel ions in the acidic microenvironment, allowing the antitumor effect to be further enhanced. This acid-responsive LDH film also shows a good antibacterial effect against S. aureus and E. coli. Besides, the LDH film prepared without the introduction of additional elements maintains low toxicity to normal cells in a normal physiological environment. This work offers some guidance for the design of a practical nickel-titanium alloy stent for the interventional treatment of tumors.

Design and Synthesis of Transferrable Macro-Sized Continuous Free-Standing Metal-Organic Framework Films for Biosensor Device.

Metal organic framework (MOF) films have attracted abundant attention due to their unique characters compared with MOF particles. But the high-temperature reaction and solvent corrosion limit the preparation of MOF films on fragile substrates, hindering further applications. Fabricating macro-sized continuous free-standing MOF films and transferring them onto fragile substrates are a promising alternative but still challenging. Here, a universal strategy to prepare transferrable macro-sized continuous free-standing MOF films with the assistance of oxide nanomembranes prepared by atomic layer deposition and studied the growth mechanism is developed. The oxide nanomembranes serve not only as reactant, but also as interfacial layer to maintain the integrality of the free-standing structure as the stacked MOF particles are supported by the oxide nanomembrane. The centimeter-scale free-standing MOF films can be transferred onto fragile substrates, and all in one device for glucose sensing is assembled. Due to the strong adsorption toward glucose molecules, the obtained devices exhibit outstanding performance in terms of high sensitivity, low limit of detection, and long durability. This work opens a new window toward the preparation of MOF films and MOF film-based biosensor chip for advantageous applications in post-Moore law period.

Controllable ion design in flexible metal organic framework film for performance regulation of electrochemical biosensing.

The limitations of solvent residues, unmanageable film growth regions, and substandard performance impede the extensive utilization of metal-organic framework (MOF) films for biosensing devices. Here, we report a strategy for ion design in gas-phase synthesized flexible MOF porous film to attain universal regulation of biosensing performances. The key fabrication process involves atomic layer deposition of induced layer coupled with lithography-assisted patterning and area-selective gas-phase synthesis of MOF film within a chemical vapor deposition system. Sensing platforms are subsequently formed to achieve specific detection of H2O2, dopamine, and glucose molecules by respectively implanting Co, Fe, and Ni ions into the network structure of MOF films. Furthermore, we showcase a practical device constructed from Co ions-implanted ZIF-4 film to accomplish real-time surveillance of H2O2 concentration at mouse wound. This study specifically elucidates the electronic structure and coordination mode of ion design in MOF film, and the obtained knowledge aids in tuning the electrochemical property of MOF film for advantageous sensing devices.

L-arginine loading porous PEEK promotes percutaneous tissue repair through macrophage orchestration.

Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lack of effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, and osseointegration. In this work, l-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK) surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) are produced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteria sterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), which promotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples could polarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results in vivo show that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. In summary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming, providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a new idea to design percutaneous implantation materials.

A Novel Nanozyme to Enhance Radiotherapy Effects by Lactic Acid Scavenging, ROS Generation, and Hypoxia Mitigation.

Uveal melanoma (UM) is a leading intraocular malignancy with a high 5-year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe-layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types.

Novel Palladium Hydride Surface Enabling Simultaneous Bacterial Killing and Osteogenic Formation through Proton Capturing and Activation of Antioxidant System in Immune Microenvironments.

Achieving bacterial killing and osteogenic formation on an implant surface rarely occurs. In this study, a novel surface design-a palladium hydride (PdHx) film that enables these two distinct features to coexist is introduced. The PdHx lattice captures protons in the extracellular microenvironment of bacteria, disrupting their normal metabolic activities, such as ATP synthesis, nutrient co-transport, and oxidative stress. This disruption leads to significant bacterial death, as evidenced by RNA sequence analysis. Additionally, the unique enzymatic activity and hydrogen-loading properties of PdHx activate the human antioxidant system, resulting in the rapid clearance of reactive oxygen species. This process reshapes the osteogenic immune microenvironment, promoting accelerated osteogenesis. These findings reveal that the downregulation of the NOD-like receptor signaling pathway is critical for activating immune cells toward M2 phenotype polarization. This novel surface design provides new strategies for modifying implant coatings to simultaneously prevent bacterial infection, reduce inflammation, and enhance tissue regeneration, making it a noteworthy contribution to the field of advanced materials.

Metainterface Heterostructure Enhances Sonodynamic Therapy for Disrupting Secondary Biofilms.

Implant-related secondary infections are a challenging clinical problem. Sonodynamic therapy (SDT) strategies are promising for secondary biofilm infections by nonsurgical therapy. However, the inefficiency of SDT in existing acoustic sensitization systems limits its application. Therefore, we take inspiration from popular metamaterials and propose the design idea of a metainterface heterostructure to improve SDT efficiency. The metainterfacial heterostructure is defined as a periodic arrangement of heterointerface monoclonal cells that amplify the intrinsic properties of the heterointerface. Herein, we develop a TiO2/Ti2O3/vertical graphene metainterface heterostructure film on titanium implants. This metainterface heterostructure exhibits extraordinary sonodynamic and acoustic-to-thermal conversion effects under low-intensity ultrasound. The modulation mechanisms of the metainterface for electron accumulation and separation are revealed. The synergistic sonodynamic/mild sonothermal therapy disrupts biofilm infections (antibacterial rates: 99.99% for Staphylococcus aureus, 99.54% for Escherichia coli), and the osseointegration ability of implants is significantly improved in in vivo tests. Such a metainterface heterostructure film lays the foundation for the metainterface of manipulating electron transport to enhance the catalytic performance and holding promise for addressing secondary biofilm infections.

A Mesoporous Silica-Loaded Multi-Functional Hydrogel Enhanced Tendon Healing via Immunomodulatory and Pro-Regenerative Effects.

Tendon injuries are pervasive orthopedic injuries encountered by the general population. Nonetheless, recovery after severe injuries, such as Achilles tendon injury, is limited. Consequently, there is a pressing need to devise interventions, including biomaterials, that foster tendon healing. Regrettably, tissue engineering treatments have faced obstacles in crafting appropriate tissue scaffolds and efficacious nanomedical approaches. To surmount these hurdles, an innovative injectable hydrogel (CP@SiO2), comprising puerarin and chitosan through in situ self-assembly, is pioneered while concurrently delivering mesoporous silica nanoparticles for tendon healing. In this research, CP@SiO2 hydrogel is employed for the treatment of Achilles tendon injuries, conducting extensive in vivo and in vitro experiments to evaluate its efficacy. This reults demonstrates that CP@SiO2 hydrogel enhances the proliferation and differentiation of tendon-derived stem cells, and mitigates inflammation through the modulation of macrophage polarization. Furthermore, using histological and behavioral analyses, it is found that CP@SiO2 hydrogel can improve the histological and biomechanical properties of injured tendons. This findings indicate that this multifaceted injectable CP@SiO2 hydrogel constitutes a suitable bioactive material for tendon repair and presents a promising new strategy for the clinical management of tendon injuries.

Biocompatible and freestanding anatase TiO2 nanomembrane with enhanced photocatalytic performance.

Biocompatible and freestanding TiO2 nanotube membranes with improved photocatalytic activity were fabricated through a water-vapour-assisted annealing treatment at relatively low temperatures. Photoluminescence results and structure characterization prove that the obtained TiO2 nanotube membranes not only possess an enhanced anatase crystallinity from water molecule-intermediated dissolution-precipitation reactions, but are also covered with abundant hydroxyl groups which are hardly influenced by external disturbances. The anatase crystallinity, the superficial hydroxyl groups and the nanotubular morphology of the membrane treated with water vapour thus lead to enhancement in photocatalytic activity. This new approach is simple and time-saving, opening up new opportunities in various areas, including tissue-engineering, watersplitting, dye-sensitized solar cells and photocatalysis.