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Recent advances and future challenges in the use of nanoparticles for the dispersal of infectious biofilms

journal of Materials Science & Technology 2021年第25期84卷 208-218页

作者： Shuang Tian Henny C.van der Mei Yijin Ren henk j.busscher Linqi Shi State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer Materials of Ministry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai UniversityTianjin300071China University of Groningen and University Medical Center Groningen Department of Biomedical EngineeringAntonius Deusinglaan 19713 AVGroningenthe Netherlands University of Groningen and University Medical Center Groningen Department of OrthodonticsHanzeplein 19700 RBGroningenthe Netherlands

Increasing occurrence of intrinsically antimicrobial-resistant,human pathogens and the protective biofilm-mode in which they grow,dictates a need for the alternative control of infectious *** bacteria utilize dispersal mechanisms to detach parts of a biofilm as part of the biofilm life-cycle during times of nutrient scarcity or *** here identify recent advances and future challenges in the development of dispersants as a new infection-control ***(DNase)and other extracellular enzymes can disrupt the extracellular matrix of a biofilm to cause ***,a variety of small molecules,reactive oxygen species,nitric oxide releasing compounds,peptides and molecules regulating signaling pathways in biofilms have been described as *** their own,dispersants do not inhibit bacterial growth or kill bacterial *** natural,as well as artificial dispersants,are unstable and hydrophobic which necessitate their encapsulation in smart nanocarriers,like p H-responsive micelles,liposomes or *** on their composition,nanoparticles can also possess intrinsic dispersant *** dispersed from an infectious biofilm end up in the blood circulation where they are cleared by host immune ***,this sudden increase in bacterial concentration can also cause *** antibiotic loading of nanoparticles with dispersant properties or combined administration of dispersants and antibiotics can counter this ***,biofilm remaining after dispersant administration appears more susceptible to existing *** part of the natural biofilm life-cycle,no signs of"dispersant-resistance"have been *** are therewith promising for the control of infectious biofilms.

关键词： Dispersant Enzymes EPS eDNA Antibiotic resistance Dispersal mechanism Nanoparticles

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In vivo biofilm formation on stainless steel bonded retainers during different oral health-care regimens

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International journal of Oral Science 2015年第1期7卷 42-48页

作者： Marije A jongsma Henny C van der Mei jelly Atema-Smit henk j busscher Yijin Ren Department of Orthodontics University of Groningen and University Medical Centre Department of Biomedical Engineering University of Groningen and University Medical Centre

Retention wires permanently bonded to the anterior teeth are used after orthodontic treatment to prevent the teeth from relapsing to pre-treatment positions. A disadvantage of bonded retainers is biofilm accumulation on the wires, which produces a higher incidence of gingival recession, increased pocket depth and bleeding on probing. This study compares in vivo biofilm formation on single-strand and multi-strand retention wires with different oral health-care regimens. Two-centimetre wires were placed in brackets that were bonded to the buccal side of the first molars and second premolars in the upper arches of 22 volunteers. Volunteers used a selected toothpaste with or without the additional use of a mouthrinse containing essential oils. Brushing was performed manually. Regimens were maintained for 1 week, after which the wires were removed and the oral biofilm was collected to quantify the number of organisms and their viability, determine the microbial composition and visualize the bacteria by electron microscopy. A 6-week washout period was employed between regimens. Biofilm formation was reduced on single-strand wires compared with multi-strand wires; bacteria were observed to adhere between the strands. The use of antibacterial toothpastes marginally reduced the amount of biofilm on both wire types, but significantly reduced the viability of the biofilm organisms. Additional use of the mouthrinse did not result in significant changes in biofilm amount or viability. However, major shifts in biofilm composition were induced by combining a stannous fluoride- or triclosan-containing toothpaste with the mouthrinse. These shifts can be tentatively attributed to small changes in bacterial cell surface hydrophobicity after the adsorption of the toothpaste components, which stimulate bacterial adhesion to the hydrophobic oil, as illustrated for a Streptococcus mutans strain.

关键词： antimicrobials biofilm bonded retention wires mouthrinse orthodontics

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Osteoblast integration of dental implant materials after challenge by sub-gingival pathogens: a co-culture study in vitro

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International journal of Oral Science 2015年第4期7卷 250-258页

作者： Bingran Zhao Henny C van der Mei Minie Rustema-Abbing henk j busscher Yijin Ren Department of Orthodontics University of Groningen and University Medical Center Groningen Department of Biomedical Engineering University of Groningen and University Medical Center Groningen

Sub-gingival anaerobic pathogens can colonize an implant surface to compromise osseointegration of dental implants once the soft tissue seal around the neck of an implant is broken. In vitro evaluations of implant materials are usually done in monoculture studies involving either tissue integration or bacterial colonization. Co-culture models, in which tissue cells and bacteria battle simultaneously for estate on an implant surface, have been demonstrated to provide a better in vitro mimic of the clinical situation. Here we aim to compare the surface coverage by U2OS osteoblasts cells prior to and after challenge by two anaerobic sub-gingival pathogens in a co-culture model on differently modified titanium （Ti）, titanium-zirconium （TiZr） alloys and zirconia surfaces. Monoculture studies with either U2OS osteoblasts or bacteria were also carried out and indicated significant differences in biofilm formation between the implant materials, but interactions with U2OS osteoblasts were favourable on all materials. Adhering U2OS osteoblasts cells, however, were significantly more displaced from differently modified Ti surfaces by challenging sub-gingival pathogens than from TiZr alloys and zirconia variants. Combined with previous work employing a co-culture model consisting of human gingival fibroblasts and supra-gingival oral bacteria, results point to a different material selection to stimulate the formation of a soft tissue seal as compared to preservation of osseointegration under the unsterile conditions of the oral cavity.

关键词： biofilm co-culture dental implant osteoblasts sub-gingival pathogens titanium-zirconium alloy

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Possibilities and impossibilities of magnetic nanoparticle use in the control of infectious biofilms

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journal of Materials Science & Technology 2021年第10期69卷 69-78页

作者： Kecheng Quan Zexin Zhang Yijin Ren henk j.busscher Henny C.van der Mei Brandon W.Peterson College of Chemistry Chemical Engineering and Materials ScienceSoochow UniversitySuzhou215123China University of Groningen and University Medical Center Groningen Department of Biomedical Engineering9713 AVGroningenthe Netherlands University of Groningen and University Medical Center Groningen Department of OrthodonticsHanzeplein 19713 GZGroningenthe Netherlands

Targeting of chemotherapeutics towards a tumor site by magnetic nanocarriers is considered promising in *** nanoparticles are also considered for use in infection-control as a new means to prevent antimicrobial resistance from becoming the number one cause of death by the year *** this end,magnetic nanoparticles can either be loaded with an antimicrobial for use as a delivery vehicle or modified to acquire intrinsic antimicrobial *** nanoparticles can also be used for the local generation of heat to kill infectious *** appealing for tumor-and infectioncontrol,injection in the blood circulation may yield reticuloendothelial uptake and physical obstruction in organs that yield reduced targeting *** can be prevented with suitable surface ***,precise techniques to direct magnetic nanoparticles towards a target site are *** problem of precise targeting is aggravated in infection-control due to the micrometer-size of infectious biofilms,as opposed to targeting of nanoparticles towards centimeter-sized *** review aims to identify possibilities and impossibilities of magnetic targeting of nanoparticles for *** first review targeting techniques and the spatial resolution they can achieve as well as surface-chemical modifications of magnetic nanoparticles to enhance their targeting efficiency and antimicrobial *** is concluded that targeting problems encountered in tumor-control using magnetic nanoparticles,are neglected in most studies on their potential application in *** biofilm targeting by smart,self-adaptive and pH-responsive,antimicrobial nanocarriers for instance,seems easier to achieve than magnetic *** leads to the conclusion that magnetic targeting of nanoparticles for the control of micrometer-sized infectious biofilms may be less promising than initially ***,using propulsion rather than pr

关键词： Magnetic nanoparticles Magnetic targeting Biofilm Infection Antimicrobials

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Maintaining sidedness and fluidity in cell membrane coatings supported on nano-particulate and planar surfaces

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Bioactive Materials 2024年第2期32卷 344-355页

作者： Sidi Liu Yuanfeng Li Linqi Shi jian Liu Yijin Ren jon D.Laman Henny C.van der Mei henk j.busscher jiangsu Key Laboratory for Carbon-Based Functional Materials&Devices Institute of Functional Nano&Soft Materials(FUNSOM)Collaborative Innovation Center of Suzhou Nano Science and TechnologySoochow University199 Ren’ai RoadSuzhou215123PR China University of Groningen and University Medical Center Groningen Department of Biomedical EngineeringAntonius Deusinglaan 19713 AVGroningenthe Netherlands Translational Medicine Laboratory The First Affiliated Hospital of Wenzhou Medical University WenzhouZhejiang325035PR China State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer MaterialsMinistry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai University94 Weijin RoadTianjin300071PR China University of Groningen and University Medical Center Groningen Department of OrthodonticsHanzeplein 19700 RBGroningenthe Netherlands University of Groningen and University Medical Center Groningen Department of Pathology and Medical BiologyHanzeplein 19700 RBGroningenthe Netherlands

Supported cell membrane coatings meet many requirements set to bioactive nanocarriers and materials,provided sidedness and fluidity of the natural membrane are maintained upon ***,the properties of a support-surface responsible for maintaining correct sidedness and fluidity are ***,we briefly review the properties of natural membranes and membrane-isolation methods,with focus on the asymmetric distribution of functional groups in natural membranes(sidedness)and the ability of molecules to float across a membrane to form functional domains(fluidity).This review concludes that hydrophilic sugar-residues of glycoproteins in the outer-leaflet of cell membranes direct the more hydrophobic inner-leaflet towards a support-surface to create a correctly-sided membrane coating,regardless of electrostatic double-layer *** positively-charged support-surfaces however,strong,electrostatic double-layer attraction of negatively-charged membranes can impede homogeneous *** correctly-sided membrane coatings,fluidity is maintained regardless of whether the surface carries a positive or negative ***,membranes are frozen on positively-charged,highly-curved,small nanoparticles and localized nanoscopic structures on a *** leaves an unsupported membrane coating in between nanostructures on planar support-surfaces that is in dual-sided contact with its aqueous environment,yielding enhanced fluidity in membrane coatings on nanostructured,planar support-surfaces as compared with smooth ones.

关键词： Bacteria Cells Hydrophobicity Lipids Membrane fluidity Membrane isolation Membrane sidedness Nanocarriers Toll-like receptors Zeta potentials

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In-biofilm generation of nitric oxide using a magnetically-targetable cascade-reaction container for eradication of infectious biofilms

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Bioactive Materials 2022年第8期7卷 321-334页

作者： Guang Yang Da-Yuan Wang Yong Liu Fan Huang Shuang Tian Yijin Ren jianfeng Liu Yingli An Henny C.van der Mei henk j.busscher Linqi Shi State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer MaterialsMinistry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai UniversityTianjin300071PR China University of Groningen and University Medical Center Groningen Department of Biomedical EngineeringAntonius Deusinglaan 19713AVGroningenthe Netherlands University of Groningen and University Medical Center Groningen Department of OrthodonticsHanzeplein 19700RBGroningenthe Netherlands Key Laboratory of Radiopharmacokinetics for Innovative Drugs Chinese Academy of Medical Sciencesand Institute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin300192PR China

Cascade-reaction chemistry can generate reactive-oxygen-species that can be used for the eradication of infectious ***,suitable and sufficient oxygen sources are not always available near an infection site,while the reactive-oxygen-species generated are ***,we developed a magnetic cascade-reaction container composed of mesoporous Fe_(3)O_(4)@SiO_(2) nanoparticles containing glucose-oxidase and L-arginine for generation of ***-oxidase was conjugated with APTES facilitating coupling to Fe_(3)O_(4)@SiO_(2) nanoparticles and generation of H_(2)O_(2) from glucose.L-arginine was loaded into the nanoparticles to generate NO from the H_(2)O_(2) *** an externally-applied magnetic field,cascade-reaction containers could be homogeneously distributed across the depth of an infectious ***-reaction containers with coupled glucose-oxidase were effective in killing planktonic,Gram-positive and Gram-negative *** efficacy of the L-arginine based second cascade-reaction was only observed when H_(2)O_(2) as well as NO were generated *** vivo accumulation of cascade-reaction containers inside abdominal Staphylococcus aureus biofilms upon magnetic targeting was observed real-time in living mice through an implanted,intra-vital ***,vancomycin-resistant,abdominal *** biofilms could be eradicated consuming solely endogenous glucose,without any glucose ***,a new,non-antibiotic-based infection-control strategy has been provided,constituting a welcome addendum to the shrinking clinical armamentarium to control antibiotic-resistant bacterial infections.

关键词： Magnetic nanoparticles Bacterial infection Glucose Reactive-oxygen-species Intra-vital window

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Bacterial outer membrane vesicles for targeted treatment of bacterial infections

Bacterial outer membrane vesicles for targeted treatment of ...

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ASTF2023（第五届）抗菌科学与技术论坛

作者： Henny C.van der Mei Rui Shi Ziliang Dong Chongqing Ma Renfei Wu Rui Lv Sidi Liu Yijin Ren Zhuang Liu jian Liu henk j.busscher University of Groningen University Medical Center Groningen Soochow University

Bacterial infections play an important role in human *** bacterial infections of internal organs are characterized by a rapid onset and severe consequences,making them a significant threat to human *** drug accumulation at the site of infection and inadequate intracellular delivery pose important obstacles,impeding the efficacy of infection *** treatment strategies to enhance the therapeutic effect of current antibiotics need to be ***-derived biological nanocarriers such as outer-membrane vesicles(OMVs) are promising nanocarriers for drug-delivery,but low harvesting yield constitute an *** we used PEGylated magnetic iron-oxide nanoparticles(MNPs) to increase their uptake by Escherichia coli,which increased their OMVs *** OMVs could be magnetically harvested at 60-fold higher yields than achieved by *** OMVs containing MNPs accumulated throughout the whole biofilm in an applied magnetic field in contrast to OMVs without MNPs which only accumulated on the outside of the ***,magnetic OMVs bear potential for use as a drug carrier with the advantage that they can be magnetically targeted to an infection *** of magnetic OMV use in an animal model is only useful if animals enter a study in an equally sick conditions as humans when they decide to go to a *** infection that proceeds extremely fast to a life-threatening conditions for which the use of magnetic OMVs could be useful is *** addition,meningitis is extremely difficult to treat due to the fact that antimicrobials need to cross the blood-brain ***,the potential of magnetic OMVs as a nanocarrier was demonstrated in a murine meningitis model,showing positive results.

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负载抗生素pH响应性胶束用于靶向杀灭悬浮细菌和生物膜

负载抗生素pH响应性胶束用于靶向杀灭悬浮细菌和生物膜

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2015年全国高分子学术论文报告会

作者：刘勇赵炳然张珍坤 henk j.busscher Yijin Ren 史林启南开大学药物化学与生物学功能高分子材料教育部重点实验室

生物膜中的胞外聚合物（extracellular polymeric substances（EPS））基质能够保护里面的细菌抵御剧烈的环境变化以及外加抗生素。因此发展新的药物投递体系以及抗生物膜效率评价体系显得尤为重要。我们将商业化的抗生素三氯生（Triclo... 详细信息

生物膜中的胞外聚合物（extracellular polymeric substances（EPS））基质能够保护里面的细菌抵御剧烈的环境变化以及外加抗生素。因此发展新的药物投递体系以及抗生物膜效率评价体系显得尤为重要。我们将商业化的抗生素三氯生（Triclosan,TS）或者荧光探针（尼罗红,NR）包载于有p H响应性的复合胶束。两种菌株绿色荧光蛋白基因转染的金黄色葡萄球菌（*** GFP）以及生物发光的*** Xen36。实验证明我们的复合胶束在pH 6.5左右有明显的p H转变现象。在弱酸性条件下,复合胶束带有正点的表面电荷,因此可以同具有负电表面电荷的细菌细胞膜和生物膜有很强的静电相互作用。抗菌实验证明我们的抗生素负载的胶束有很好的抑制细菌生长和杀灭细菌的能力。更为重要的是,我们利用活体成像仪（IVIS imaging system）作为一种无创的,实时的监测手段用来评价不同p H条件下和不同的时间点抗生物膜的能力。

关键词：复合胶束抗生素投递 pH响应性生物膜靶向投递

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