Inorganic non-metallic biomaterial is one of main types of biomaterials, which is widely used in biomedical fields such as tissue repair, tumor therapy, and drug delivery., making an important contribution to national life and health. Research on inorganic non-metallic biomaterials in China is flourishing, but their production and application are still in the stage of overcoming difficulties. To realize the high-quality development of China's inorganic non-metallic biomaterials and improve their hard power to protect national life and health, this paper analyzes hotspots and difficult problems in research and application of China's inorganic non-metallic biomaterials by means of strategic study. Based on current development opportunities and challenges, some suggestions are proposed for the development of inorganic non-metallic biomaterials, such as material design for unique performance, research on materiobiology, exploration of new principles and mechanisms mediated by materials, customization by intelligent personalization, design through big data screening and artificial intelligence, and standardization based evaluation/regulation. This aims to provide guidance for development of inorganic non-metallic biomedical products and push forward scientific research while accumulating talent resources.

Dental resins are currently the most commonly used filling materials for dental caries clinically due to their advantages of aesthetics, safety, and easy operation. However, their service life is limited because of their low mechanical strength and insufficient antibacterial activity. In this study, radial mesoporous silica was prepared firstly, and then loaded nanosilver into its porous channels to obtain silver loaded radial mesoporous silica (Ag-RMS). Effects of different contents of Ag-RMS on antibacterial, mechanical, and physicochemical properties of dental composite resins were studied. The results showed that Ag-RMS could significantly improve the antibacterial performance of composite resins, achieving an antibacterial rate of 99.68% against Streptococcus mutans when the addition amount of Ag-RMS was 5% (mass fraction). Mechanical strength of the composite resin gradually increased with the increase of Ag-RMS content. When the addition amount of Ag-RMS reached 7% (in mass), the flexural strength of composite resins was 28.16% higher than that of resin matrix. Moreover, the addition of Ag-RMS had almost no obvious effect on their polymerization shrinkage rate, monomer conversion rate, curing depth, and surface hydrophobicity. These results indicate that the prepared Ag-RMS in this study can improve the comprehensive performance of the novel composite resins.

Compared with antibiotics and other drugs with poor functionalities and risk to induce bacterial resistance, inorganic functional nanomaterials with catalytic activity occupy an increasingly important position in the treatment of pathogenic infections by advantages of high response to the infected microenvironment (e.g. weak acid, high H₂O₂ concentration) or external physical stimuli (e.g. laser, ultrasound) and broad-spectrum sterilization. However, the acidic infection microenvironment is weak and unstable, and light or sound signals with high power density will cause damage to human cells. In addition, antimicrobial applications of alternative magnetic field (AMF), a non-invasive signal type with high tissue penetration, convenience to be remotely controlled, and effective magnetoelectric catalysis based on AMF have not been reported. In this study, an AMF-responsive nanocatalytic strategy based on the magnetostrictive-piezoelectric catalytic effect was applied to antibacterial research, and the surface of CoFe₂O₄-BiFeO₃ magnetoelectric nanoparticles (BCFO) was modified with the nitrogen-containing group L-arginine (LA) to achieve a magneto-electric responsive controlled release of powerful bactericide reactive nitrogen species (RNS). In AMF, BCFO simultaneously generates reactive oxygen species (ROS) hydroxyl radical (·OH) and superoxide anion (·O₂^-). The former reacts with LA to release nitric oxide (NO), and the latter combines with NO to produce peroxynitrite (ONOO^-), a typical RNS. As a highly active nitrification and oxidation agent, ONOO^- could exhibit stronger antibacterial activity than ROS under biofriendly AMF. Successful production of ONOO^- and achievement of stronger bactericidal efficiency were validated in this study. This work not only applies magnetoelectric nanocatalysis for antibacterial purposes, but also significantly improves the antibacterial ability through the conversion of ROS to RNS.

Currently, repair of infectious bone defects is still a clinical serious challenge. Here, a heterojunction coating of niobium oxide on pure niobium surface by using microarc oxidation and hydrothermal treatment was prepared. The results showed that the obtained heterogeneous junctions exhibited synchronously enzyme-like and ultrasonic dynamic properties triggered by ultrasound treatment, especially in acidic microenvironment of mimic bacterial infection. Under these key conditions, oxidase-like activity of the heterogeneous junctions was enhanced, generating several reactive oxygen species which can kill bacteria and remove their biofilm, with inhibition and clearance rates were 98.57% and 91.43%, respectively. Under simulated physiological conditions, ultrasound enhanced antioxidant-like enzyme activity of this kind heterogeneous junction, thereby scavenging reactive oxygen species, alleviating oxidative stress, and promoting proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (rBMSCs). In conclusion, the obtained niobium-based coatings with sonodynamic and enzyme-like activities have profound potential application prospects in infectious bone repair.

Systemic metastasis of cancer cells is currently the main cause of death for patients with advanced cancer. Due to the rapid proliferation of tumor cells and abnormal deposition of extracellular matrix, the large-volume tumor tissue in advanced cancer is dense and stiff, which brings great difficulties to the treatment of advanced solid tumors: conventional drugs having difficulty in penetrating and immune cells facing challenges to infiltrate into their interior. Meanwhile, tumor cells on hard matrices have stronger invasive ability, which is prone to cause systemic metastasis of tumors. To solve this problem, this study prepared ethylenediaminetetraacetic acid (EDTA) intercalated zinc-aluminum layered double hydroxide nanomaterials (EDTA/LDH). Based on two parallel Ca²⁺ deprivation mechanism, the anti-metastasis immunotherapy of EDTA/LDH material system for advanced large-volume solid tumors was studied. In the slightly acidic tumor microenvironment, the material system adheres to the tumor cell membrane through electrostatic force, releases EDTA to chelate Ca²⁺ in cell adhesion proteins, cuts off part of the cell connections, reduces the stiffness of large tumors, and promotes the infiltration of immune cells into the tumor tissue. In addition, the material system is phagocytosed by macrophages as a "foreign body", causing calcium store-operated calcium influx, activating the anti-tumor immune effect of macrophages, and inhibiting the tumor-promoting invasion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and regulatory T cells (Tregs). This study will provide reference ideas and methods for the anti-metastasis treatment of advanced malignant solid tumors.

Ferroferric oxide (Fe₃O₄) magnetic nanoparticles are widely used as passive targeting carriers in gene therapy, due to their simple preparation, targeting under external magnetic field and easy surface grafting. This study synthesized oil phase Fe₃O₄ nanoparticles with controllable particle sizes in the range from 4 to 9 nm by regulating the accumulation growth time in the solvothermal method. Then, meso-2, 3-dimercaptosuccinic (DMSA) was employed to double exchange oleic acid molecules on its surface to provide good water dispersibility. Finally, Fe₃O₄-DMSA-PEI magnetic nanoparticles were obtained by grafting branched polyethylenimine (PEI) onto Fe₃O₄-DMSA surface through amidization reaction. The results demonstrate that the Fe₃O₄-DMSA-PEI magnetic nanoparticles have a surface Zeta potential of (52.50 ± 1.94) mV, remaining a certain degree of superparamagnetism (14.48 emu/g, 1 emu/g=1 A∙m²/kg). When the mass ratio of Fe₃O₄-DMSA-PEI magnetic nanoparticles to plasmid DNA is 15 : 1, it can completely block DNA and its loading capacity is as high as 6.67%. The Fe₃O₄-DMSA-PEI magnetic nanoparticles prepared in this study have a certain gene delivery ability and are expected to be used as gene carriers in the field of gene transfection.

Chemodynamic therapy (CDT) uses endogenous H₂O₂ of tumor cells to react with Fenton catalysts to generate highly toxic hydroxyl radical (•OH), thereby killing cancer cells. However, the insufficient endogenous H₂O₂ and low transport efficiency of nanoparticles result in unsatisfactory anticancer efficacy. Here, we successfully synthesized a Cu²⁺ doped mesoporous silica nanoparticles (Cu-MSN) with excellent dispersity and small size. After loaded with doxorubicin (DOX) and ascorbate (AA), Cu-MSN was coated with folic acid (FA), dimethyl maleic anhydride (DMMA) modified chitosan (FA-CS-DMMA) and carboxymethyl chitosan (CMC) to obtain a pH responsive targeted nanocatalyst FCDC@Cu-MSN@DA. SEM images showed that particle size of FCDC@Cu-MSN@DA was about 100 nm. After 48 h in vitro, cumulative amount of Cu²⁺ release reached 80% and DOX release was about 57.3% in the acidic environment. After oxidation of AA, the produced exogenous H₂O₂ induced Cu²⁺ to catalytic the Fenton-like reaction, which enhanced the therapeutic effect of tumor chemodynamic therapy (CDT). Cell experiments in vitro demonstrated that FCDC@Cu-MSN@DA exhibited excellent anticancer ability in the combination of CDT and chemotherapy. This multifunctional nanocatalyst has great potential application in cancer therapy in the future.

Titanium orthopaedic implants present a risk of infection and require the development of antibacterial, but still biocompatible and non-resistant coatings. Magnesium oxide (MgO) coatings were prepared on micro-arc oxidized titanium by electrophoretic deposition for 15, 30, 45, or 60 s. Nano-sized MgO particles agglomerated to form homogeneous coatings with surface coverage increasing with the duration of deposition. The four groups produced antibacterial rates of 1%, 69%, 83%, and 84% after co-cultured with S. aureus for 6 h, and 81%, 86%, 89%, and 98% after co-cultured for 24 h. Electron and fluorescence microscopies showed decreasing density of bacterial cells and proportion of living cells with increasing time of deposition. Mouse osteoblasts seeded on the four groups had survival rates of 108%, 89%, 53%, and 27% on day 1, and 139%, 117%, 112%, and 66% on day 5. Proportion of dead cells on the coated samples increased with increasing time of deposition but less than 5% on day 5. These results indicate that MgO coatings prepared by electrophoretic deposition for 30 s is reasonable in vitro antibacterial activities and cytocompatibility.

Pulp capping agents are effective materials which can preserve dental pulp and treat caries in different ways. It is urgently demanded to establish a guidance to select the appropriate pulp capping agents according to the conditions of pulp and cary requirements. In this work, morphology, composition, physical, and chemical properties of three commonly used clinical pulp capping agents, namely dental zinc oxide eugenol cement (ZnO), self-curing calcium hydroxide (Dycal), and light-curing calcium hydroxide (Calcimol), were studied. Their antibacterial, cytocompatibility and blood compatibility were evaluated. The results showed that ZnO was hydrophobic and its effective component, crystallized ZnO, could consistently release zinc ions, giving its alkaline environment to inhibit bacteria. Structure, morphology and components in Dycal were similar to those in Calcimol. However, its surface was more hydrophobic and its release amount of calcium ions was larger than that of Calcimol. It formed an alkaline micro-environment, thereby possessed good antibacterial ability and biocompatibility. Meanwhile, Calcimol was hydrophilic and convenient to operate, and released less metal ions. Due to its safe composition, Calciomol exhibited excellent biocompatibility but slightly weaker antibacterial property. Our results suggested that these comparative results might be a useful clinical guidance for selecting appropriate pulp capping agents according to the degree of caries and the health status of dental pulp to treat the caries.

Natural enzymes play an important role in maintaining normal life activities, but suffer in their inherent instability, harsh reaction conditions and high purification costs, which limit their wide applications in vitro. Compared to natural enzymes, nanozymes with high stability, low cost, and ease of structural regulation and modification attract the great interests and are widely applied to biomedicine, environmental control, industrial production and other fields due to their enzyme-like activities and selectivity. As an essential element and one of the active central metals of natural enzymes in the human body, copper-based (Cu-based) nanozymes have received extensive attentions and researches. This review focused on the classification of Cu-based nanozymes, such as Cu nanozymes, Cu oxide nanozymes, Cu telluride nanozymes, Cu single-atom nanozymes, and Cu-based metal organic framework nanozymes. Then this review described the enzyme-like activities and catalytic mechanisms of Cu-based nanozymes, and also summarized the applications of Cu-based nanozymes, including biosensing, wound healing, acute kidney injury, and tumors. The challenges and future development direction of Cu-based nanozymes were proposed.

Hypochlorous acid (HClO) is one of the reactive oxygen species (ROS), taking crucial parts in many physiological and pathological processes. However, excessive HClO causes tissue injuries, atherosclerosis, neurodegeneration diseases, and even cancers. Therefore, real-time detection of HClO in cancer cells is of importance for exploring the effect of HClO in tumor progression or immunotherapy. Quite different from present organic molecular probes, a novel inorganic-based hydrophilic fluorescent nanoprobe was developed by simply integrating fluorescein isothiocyanate (FITC) into hollow mesoporous Prussian Blue nanoparticles (HMPB) in this work. Owing to inner filter effect, fluorescence of FITC within HMPB quenches to some extent, which can be restored via the Fe²⁺-ClO^- redox reaction. A typical fluorescence increase of FITC at emission peak of 520 nm can be clearly observed in the presence of HClO in vitro, which exhibits a good linear relationship in the range of 5×10^-6-50×10^-6 mol/L in HClO detection and its detection limit is calculated to be 2.01×10^-6 mol/L. Furthermore, the cellular experiment demonstrates the specific detection capability of HClO in cancer cells with high sensitivity by the obtained nanoprobe.

Bacteria and viruses always posed a threat to human health. Most impressively, SARS-CoV-2 has raged around the world for almost three years, causing huge loss to human health. Facing increasing challenges of drug-resistance and poor treatment efficacy, new solutions are urgently needed to combat pathogenic microorganisms. Recently, nanozymes with intrinsic enzyme-like activities emerged as a promising new type of “antibiotics”. Nanozymes exhibit superior antibacterial and antiviral activities under physiological conditions by efficiently catalyzing generation of a large number of reactive oxygen species. Moreover, enhanced therapeutic effects are achieved in nanozyme-based therapy aided by the unique physicochemical properties of nanomaterials such as photothermal and photodynamic effects. This paper reviews the latest research progress in the field of anti-microbial nanozymes, systematically summarizes and analyzes the principles of nanozymes in the treatment of bacteria and viruses from a mechanistic point of view. An outlook on the future direction and the challenges of new anti-microbial infection nanomaterials are proposed to provide inspiration for developing next generation anti-microbial nanozymes.