Bioceramic scaffolds with two-step internal/external modification of copper-containing polydopamine enhance antibacterial and alveolar bone regeneration capability / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Magnesium-doped calcium silicate (CS) bioceramic scaffolds have unique advantages in mandibular defect repair; however, they lack antibacterial properties to cope with the complex oral microbiome. Herein, for the first time, the CS scaffold was functionally modified with a novel copper-containing polydopamine (PDA(Cu2+‍)) rapid deposition method, to construct internally modified (*P), externally modified (@PDA), and dually modified (*P@PDA) scaffolds. The morphology, degradation behavior, and mechanical properties of the obtained scaffolds were evaluated in vitro. The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance. During the prolonged immersion stage, the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release. The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA, while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects. Finally, the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model. Overall, it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+) modification, and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

Research progress on surface modification of titanium implants by strontium ions / 口腔疾病防治

@#Traditional titanium implants do not completely meet the clinical requirements because they are bioinert. The surface of titanium implants, modified by strontium ions, can enhance osseointegration and reduce peri-implantitis. In this paper, the biological properties of titanium implant surfaces modified by strontium ions were reviewed. Strontium ions can be coated on the implant surface by hydrothermal treatment, electrochemical deposition, phosphate chemical conversion, flame-spraying, supramolecular self-assembly, magnetron sputtering, laser deposition and alkali etching. Implant surfaces modified by strontium ions can not only promote osteogenesis and early osseointegration but also inhibit bacterial growth and reduce postoperative infections. Even better osseointegration and antibacterial effects can be achieved when strontium ions are incorporated with other elements, such as silver, zinc, gallium, and calcium. However, most of the studies on the use of strontium ion-modified titanium implants are animal experiments and in vitro experiments, and the observation time is short compared with the actual service life of the implants. Thus, the conclusions obtained may be different from the actual clinical application, and the long-term effects need to be studied. In addition, the osteogenic effects of various modification methods also need to be compared. Future research can focus on the following points: ① to find efficient modification methods that can be widely used in the clinic; ②to study how to control the concentration of strontium ions near the implant to exert their biological function and reduce their toxic side effects; and ③ to conduct long-term follow-up clinical trials to observe their osteogenic and antibacterial effects.

Preparation of berberine-naringin dual drug-loaded composite microspheres and evaluation of their antibacterial-osteogenic properties / 中国修复重建外科杂志

OBJECTIVE@#To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects.@*METHODS@#The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively.@*RESULTS@#NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P>0.05).@*CONCLUSION@#NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.

Research progress on the application of antibacterial titanium alloys in stomatology / 口腔疾病防治

@#Currently, titanium alloys are widely used in the field of stomatology; however, owing to long-term exposure to a complex microbial environment, dental plaques easily form on the surface of the materials, affecting the use efficiency and the service life of the materials. The antibacterial titanium alloy is a new kind of titanium alloy with antimicrobials added through surface modification or overall modification. Based on the location of antibacterial agents in titanium alloy materials, antibacterial titanium alloys can be divided into coating and alloy types. The antibacterial effect of coated antibacterial titanium alloy is good, but the disadvantage is that most of the coatings are not wear-resistant. The widely-used antibacterial agent of the alloy type is metal elements, which can be evenly distributed in the alloy, and the antibacterial properties are stable and long-lasting. Based on whether antibacterial agents can be released, antibacterial titanium alloys can be further divided into active antibacterial and passive antibacterial types. Active antibacterial type titanium alloys can release loaded antibacterial agents, and the antibacterial effect is more obvious, but the release duration of antibacterial agents is relatively short. Passive antibacterial titanium alloys exhibit an antibacterial effect by contact sterilization or inhibition of bacterial adhesion instead of releasing antibacterial agents. The antibacterial titanium alloy can inhibit the adhesion of bacteria on the surface of the material and prolong the service life of oral orthodontic appliances, implants and titanium plates. Moreover, the mechanical properties of the titanium alloy after antibacterial modification are not significantly affected, and the addition of antibacterial agents such as hydroxyapatite can increase the osteogenic function of the material. Therefore, the alloy has good application prospects in the fields of dental implant, orthodontic treatment and oral and maxillofacial surgery. However, most of the current studies on antibacterial titanium alloys are in vitro experiments, and their long-term clinical effects and antibacterial mechanisms are still unclear and need further study.

Safety and antibacterial properties of gentamicin-loaded silk fibroin in meniscus repair / 中国组织工程研究

BACKGROUND: Silk fibroin material has good biocompatibility, excellent mechanical properties, biodegradation and other advantages. However, it has not been used as a kind of suture fixation material in the repair of meniscus tear. OBJECTIVE: To prepare gentamicin loaded silk fibroin material and analyze its biocompatibility and antibacterial properties. METHODS: After dissolving the degummed natural silkworm cocoon with ternary solution, the silk fibroin material was prepared by dialysis, freeze-drying, redissolution and molding, and gentamicin was dissolved in silk fibroin solution to prepare gentamicin loaded silk fibroin material. Silk fibroin material and gentamicin loaded silk fibroin material were co-cultured with mouse pre chondroblasts respectively. After 1, 3, and 5 days, cell proliferation was detected by MTT assay. After 24 hours of co-culture, the cytotoxic effect of the material was detected by calcein staining. The early apoptosis of cells was detected by flow cytometry. The adhesion of cells on the surface of the material was observed by scanning electron microscope. Silk fibroin material and gentamicin loaded silk fibroin material were mixed with anticoagulant separately. The hemolysis rate of the material was detected by hemolysis experiment. The silk fibroin material and gentamicin loaded silk fibroin material were co-cultured with S.aureus and E.coli respectively. The bacterial count, scanning electron microscope observation and bacteriostatic circle experiment were carried out. RESULTS AND CONCLUSION: (1) The two materials had no significant effect on cell proliferation and early apoptosis. (2) There was no obvious cytotoxicity between the two materials, and the cells adhered on the surfaces of the two materials grew well, arranged tightly, and the morphology of the cells expanded. (3) The two materials had good blood compatibility and did not cause hemolytic reaction. (4) Gentamicin loaded silk fibroin material had obvious inhibition on S.aureus and E.coli, and the inhibition on S.aureus was more obvious. (5) The results showed that the gentamicin loaded silk fibroin material has good biocompatibility and antibacterial property.

Study on pharmacodynamics and safety of self-made compound ketoconazole ointment / 药学实践杂志

Objective To evaluate the pharmacodynamics and safety of the self-made compound ketoconazole ointment. Methods Using the disk diffusion test, 6 kinds of fungi and 2 kinds of bacteria were selected to investigate the effect of the self-made ointment and 3 commercial products on the diameter of the bacteriostatic circle. In addition, the skin irritation and skin allergies of the single and multiple applications were used to evaluate the safety of the self-made ointment. Results The self-made ointment was similar to the commercial products containing ketoconazole. They all showed remarkable bacteriostatic circle against the 6 kinds of fungi. For pseudomonas aeruginosa, none of the preparations contributed to visible bacteriostatic circle. For staphylococcus aureus, the bacteriostatic circle of the self-made ointment was similar to that of commercial mupirocin ointment and was significantly larger than other commercial products. After the treatment with the self-made ointment, the score of the skin irritation was below 0.5 and the sensitization rate was 0. There was no difference in tissue structure between treated and normal skin. Conclusion The self-made compound ketoconazole ointment has better safety and better antibacterial property than the commercial products. It is expected to be used for the treatment of superficial skin fugle infections.

Development of novel self-adhesive resin cement with antibacterial and self-healing properties / 华西口腔医学杂志

OBJECTIVE@#This study aimed to develop novel self-adhesive resin cement with antibacterial and self-healing properties. Furthermore, the dentin bonding strength, mechanical properties, self-healing efficiency, and antibacterial property of the developed cement were measured.@*METHODS@#Novel nano-antibacterial inorganic fillers that contain quaternary ammonium salts with long-chain alkyls were synthesized. These fillers were added into self-adhesive resin cement containing self-healing microcapsules at mass fractions of 0, 2.5%, 5.0%, 7.5%, or 10.0%. The dentin shear bonding test was used to test the bonding strength, whereas the flexural test was used to measure the flexural strength and elastic modulus of the cement. The single-edge V-notched beam method was used to measure self-healing efficiency, and human dental plaque microcosm biofilms were chosen to calculate the antibacterial property.@*RESULTS@#The dentin shear bond strength significantly decreased when the mass fraction of the nano-antibacterial inorganic fillers in the novel cement reached 7.5% (P0.1). Resin cement containing 2.5% mass fraction or more nano-antibacterial inorganic fillers significantly inhibited the metabolic activity of dental plaque microcosm biofilms, indicating strong antibacterial potency (P<0.05).@*CONCLUSIONS@#The novel self-adhesive resin cement exhibited promising antibacterial and self-healing properties, which enable the cement to be used for dental applications.

Inhibitory effects of nano silver and titanium dioxide on the nucleic acid of staphylococcus aureus / 中华急诊医学杂志

Objective To study the effects of nano silver (Ag) and titanium dioxide (TiO2) on the content of nucleic acid in staphylococcus aureus in order to explore their antibacterial mechanisms.Methods After preparation of beef extract peptone liquid cultures,the effects of minimal inhibitory concentrations (MICs) of nano Ag and TiO2 on staphylococcus aureus strains were determined.With the 1/2 MICs nano Ag and TiO2,the contents of DNA and RNA macromolecules from staphylococcus aureus cultures were measured to determine the damage degree of staphylococcus aureus cell membranes by ultraviolet spectrophotometer,and then the fluorescence intensities of the staphylococcus aureus cells were observed under fluorescence microscope and the fluorescence values were tested by fluorescence spectrophotometer to determine the contents of nucleic acid DNA and RNA.Results The MICs of nano Ag and TiO2 were 1.6 mg/mL and 5.781 μg/mL.After treatment with the 1/2 MICs nano Ag and TiO2,nano Ag group and TiO2 group were compared with the control group (culture fluid without adding antibacterial agent),respectively,and there were no significant differences in the contents of DNA and RNA macromolecules from staphylococcus aureus cultures between n anoAg group and control group as well as between TiO2 group and control group were (P＞0.05),and there were significant decreases in fluorescence intensities and the contents of nucleic acid DNA and RNA (P＜0.01).Conclusions Nano Ag and TiO2 had obvious antibacterial effects on staphylococcus aureus and the antibacterial properties of nano Ag was stronger than that of TiO2.The antibacterial mechanisms of nano Ag and TiO2 against staphylococcus aureus may be associated with the inhibition of the synthesis of nucleic acid DNA and RNA,inhibiting protein synthesis and then bacterial growth.

Effect of water immersion on a dental self-healing and antibacterial resin composite / 华西口腔医学杂志

OBJECTIVE@#This investigation aimed to develop a novel self-healing and antibacterial dental resin composite. The effects of water immersion on its properties were also evaluated.@*METHODS@#Microcapsules filled with healing agent of triethylene glycol dimethacrylate were synthesized on the basis of previous studies. Antibacterial resin composite contained nano-antibacterial inorganic fillers that were modified by quaternary ammonium salt with long-chain alkyl. Microcapsules were incorporated into antibacterial resin composite at mass fraction of 7.5%. A commercial resin composite named Tetric N-Ceram was used as control. The resin samples were immersed in 37 °C distilled water for different periods. A flexural test was used to measure the mechanical properties of the novel resin composite. A single-edge V-notched beam method was used to measure fracture toughness and self-healing efficiency. A dental plaque microcosm biofilm model with human saliva as inoculum was formed. Colony-forming units (CFU) and lactic acid production of biofilm on the novel resin composite were calculated to test the antibacterial property.@*RESULTS@#Mechanical properties and fracture toughness decreased significantly after the composite was immersed in water for 30 days (P0.05). Water immersion did not weaken the self-healing capability of the composite (P>0.05), and self-healing efficiency of 64% could still be obtained even after 270 days. The antibacterial resin composite showed a strong inhibition effect on the biofilm metabolic activity versus water immersion time from 1 day to 270 days. Therefore, the composite could still have a promising antibacterial property even after being immersed in water (P<0.05).@*CONCLUSIONS@#Water immersion could weaken the mechanical properties of the novel self-healing and antibacterial resin composite, but it insignificantly affected the self-healing and antibacterial properties of the composite.

Antibacterial dental adhesive containing nanoantibacterial inorganic fillers / 华西口腔医学杂志

OBJECTIVE@#This investigation aimed to develop a novel antibacterial dental adhesive containing nanoantibacterial inorganic fillers and measure the dentin bonding strength, mechanical properties, and antibacterial property of the novel adhesive in vitro.@*METHODS@#Novel nanoantibacterial inorganic fillers containing quaternary ammonium salt with long chain alkyl were synthesized on the basis of previous research. These novel nanoantibacterial inorganic fillers were added into the dental adhesive to prepare novel nanoantibacterial dental resin composite at mass fractions of 0%, 2.5%, 5.0%, 7.5%, and 10%; 0% was used as control. Dentin shear bonding test was used to evaluate the bonding strength. Flexural test was utilized to measure the novel resin composite flexural strength and elastic modulus. A dental plaque microcosm biofilm model with human saliva as inoculum was formed. Colony forming unit, lactic acid production, and live/dead assay of the biofilm on novel dental adhesive were calculated to assess the effect of novel dental adhesive on human dental plaque microcosm biofilm.@*RESULTS@#The dentin shear bond strength, flexural strength, and elastic modulus were 28.9 MPa, 86.6 MPa, and 4.2 GPa, respectively, when the nanoantibacterial inorganic filler mass fraction in the dental adhesive reached approximately 5.0%. Consequently, the dentin shear bond strength and mechanical properties significantly increased. Addition of 2.5% nanoantibacterial inorganic fillers into the dental adhesive exerted no adverse effect on the mechanical properties significantly (P>0.05). Dental adhesive containing 5% or more nanoantibacterial inorganic fillers inhibited the metabolic activity of the dental plaque microcosm biofilm significantly, thereby displaying a strong antibacterial potency (P<0.05).@*CONCLUSIONS@#This novel antibacterial dental adhesive, which contained 5.0% nanoantibacterial inorganic filler, exhibited promising bonding strength, mechanical property, and antibacterial ability. Hence, this adhesive can be potentially used in caries inhibition in dental application.

The surface structure and antibacterial property of Ag-containing coating on casting cobalt chromium alloy / 实用口腔医学杂志

Objective:To study the surface structure and antibacterial property of Ag-containing coating(AgCC)on casting cobalt chromium alloy(Co-Cr).Methods:Plasma spraying technique was adopted to prepare AgCC on Co-Cr.Scanning electron microsco-py,energy dispersive analysis and X-ray diffraction analysis were used to evaluate the surface properties.The antibacterial effects of AgCC against staphylococcus aureus and candida albicans were examined by film attachment method.Fluorescence microscope was a-dopted to evaluate the bacteria adhesion property.Results:AgCC surface was uniform and compact,combined perfectly with sub-strate material.The content of the surface was mainly Ag,Cr and a small amount of Ag2 O and Cr2 O3 .The results of antibacterial as-say showed that on AgCC the number of bacterial colony was fewer(P<0.05)and bacterial adhesion was less than those on Co-Cr(P<0.05).Conclusion:AgCC surface was stable and has antibacterial property.

Study on antibacterial property of silver loaded titanium dioxide antibacterial coated endotracheal intubation tube / 中华危重病急救医学

Objective To study the antibacterial property of silver loaded titanium dioxide (TiO2) antibacterial coated endotracheal intubation tube,and to determine the minimum effective antibacterial concentration.Methods Intubation tubes coated with different concentrations of antibacterial agents were prepared with sol gel method.Polyethylene endotracheal intubation tubes were used as substrate,and silver loaded TiO2 was used as the antibacterial agent.According to the different antibacterial concentrations of the antibacterial agent,the tubes were divided into nine groups:10.0％ group,5.0％ group,2.0％ group,1.5％ group,1.0％ group,0.8％ group,0.6％ group,0.2％ group,and conrol group.They were respectively immersed in three standard bacteria suspensions with 1.0 × l05 cfu/mL:Pseudomonas aeruginosa,Staphylococcus aureus,and Escherichia coll Together with standard bacteria liquid group,there were 10 experimental groups.They were kept overnight for 24 hours.10 μL of respective culture medium was smeared on blood agar culture medium.After being cultured overnight in 35 ℃,the number of bacteria colonies was respectively counted.Results In 1.0 × 105 cfu/mL of three standard bacteria liquids with antibacterial agent concentration≥ 1.0％,three bacterial colonies had un-obviously growth rate.Almost the same strong antibacterial effects to achieve sterilizing rates of more than 98％ was shown in each group of the antibacterial coating endotracheal intubation tubes (all P＞0.05).As the antibacterial agent concentration decreased,three bacterial colonies were increasing gradually.Intermediate antibacterial effects were shown in tubes of 0.8％ group,with significant statistic difference as compared with 1.0％ and 0.6％ groups [Pseudomonas aeruginosa:7.300 (4.050,8.350) vs.0.200 (0.050,1.200),9.700 (9.000,10.000); Staphylococcus aureus:4.100 (3.300,4.650) vs.0.000 (0.000,0.150),5.800 (5.350,7.650); Escherichia coli:1.400 (0.750,3.750) vs.0.050 (0.025,0.050),9.500 (8.500,9.800),all P＜0.01].Conclusions Silver loaded TiO2 antibacterial coated endotracheal intubation tube had definite antibacterial properties,which were related to the antibacterial concentration.Strong antibacterial effects were shown when antibacterial concentration was above 1.0％,with bacteria almost completely killed in the immersing liquid.

Research progress on surface modification of titanium and titanium alloys by ion implantation / 实用口腔医学杂志

Ionimplantationtechniqueisamethodthatprocessingthematerialsurfacesinordertochangetheirsurfacechemical,physical and mechanical properties in vacuum environment.Titanium and titanium alloys modified by different types of ions can change their surface properties and characteristics,thereby improving the osseointegration and antibacterial properties of titanium implant.This review summarizes the researches of titanium implant surface modified by different ions implanting.

Antimicrobial activity and mineral composition of shiitake mushrooms cultivated on agricultural waste

The antimicrobial activity and mineral composition of shiitake mushrooms were evaluated in four isolates of Lentinula edodes. Mushrooms were cultivated on artificial logs, based on eucalyptus sawdust enriched with 20 percent rice, wheat, or soybean bran, or combination of 10 percent of two of these supplements. The substrates were humidified with a 0.1 percent mate tea extract or water. Logs of Eucalyptus grandis were also used to cultivate the shiitake mushrooms. The antimicrobial activity of an aqueous extract, corresponding to 40 mg of mushroom dry matter, was in some cases, depending on the isolate, able to inhibit both Bacillus subtilis and Escherichia coli K-12, independent of substrate composition or the growth stage of the mushrooms. Nitrogen, phosphorus, potassium, magnesium and calcium concentrations varied according to the substrate on which the mushrooms were cultivated, being, generally, higher with cultivation on artificial rather than natural eucalyptus logs. It could be concluded that, in addition to the fungal isolate, substrate composition and, processing methods must be considered during the production of antimicrobial substance(s) as well as in the mushroom nutritional composition.