The Role of Oral Cavity Biofilm on Metallic Biomaterial Surface Destruction–Corrosion and Friction Aspects

Metallic biomaterials in the oral cavity are exposed to many factors such as saliva, bacterial microflora, food, temperature fluctuations, and mechanical forces. Extreme conditions present in the oral cavity affect biomaterial exploitation and significantly reduce its biofunctionality, limiting the time of exploitation stability. We mainly refer to friction, corrosion, and biocorrosion processes. Saliva plays an important role and is responsible for lubrication and biofilm formation as a transporter of nutrients for microorganisms. The presence of metallic elements in the oral cavity may lead to the formation of electro-galvanic cells and, as a result, may induce corrosion. Transitional microorganisms such as sulfate-reducing bacteria may also be present among the metabolic microflora in the oral cavity, which can induce biological corrosion. Microorganisms that form a biofilm locally change the conditions on the surface of biomaterials and contribute to the intensification of the biocorrosion processes. These processes may enhance allergy to metals, inflammation, or cancer development. On the other hand, the presence of saliva and biofilm may significantly reduce friction and wear on enamel as well as on biomaterials. This work summarizes data on the influence of saliva and oral biofilms on the destruction of metallic biomaterials

Use of magnetic nanoparticles as a drug delivery system to improve chlorohexidine antimicrobial activity

Nanotechnology offers new tools for developing therapies to prevent and treat oral infections, particularly biofilm-dependent disorders, such as dental plaques and endodontic and periodontal diseases. Chlorhexidine (CHX) is a well-characterized antiseptic agent used in dentistry with broad spectrum activity. However, its application is limited due to inactivation in body fluid and cytotoxicity toward human cells, particularly at high concentrations. To overcome these limitations, we synthesized nanosystems composed of aminosilane-coated magnetic nanoparticles functionalized with chlorhexidine (MNP@CHX). In the presence of human saliva, MNPs@ CHX displayed significantly greater bactericidal and fungicidal activity against planktonic and biofilm-forming microorganisms than free CHX. In addition, CHX attached to MNPs has an increased ability to restrict the growth of mixed-species biofilms compared to free CHX. The observed depolarization of mitochondria in fungal cells treated with MNP@CHX suggests that induction of oxidative stress and oxidation of fungal structures may be a part of the mechanism responsible for pathogen killing. Nanoparticles functionalized by CHX did not affect host cell proliferation or their ability to release the proinflammatory cytokine, IL-8. The use of MNPs as a carrier of CHX has great potential for the development of antiseptic nanosystems.This work was supported by the National Science Center, Poland, under grant UMO-2014/15/D/NZ6/02665 (to KN). In 2016, KN was awarded a fellowship from the Foundation for Polish Science. This study was conducted with the use of equipment purchased by the Medical University of Białystok as part of the RPOWP 2007–2013 funding, Priority I, Axis 1.1, contract number UDA-RPPD.01.01.00-20-001/15-00, dated 26.06.2015.Grażyna Tokajuk - Department of Microbiological and Nanobiomedical Engineering, Medical University of Białystok; Department of Intergrated Dentistry, Medical University of BiałystokKatarzyna Niemirowicz - Department of Microbiological and Nanobiomedical Engineering, Medical University of BiałystokPiotr Deptuła - Department of Microbiological and Nanobiomedical Engineering, Medical University of Białystok; Department of Materials and Biomedical Engineering, Białystok University of TechnologyEwelina Piktel - Department of Microbiological and Nanobiomedical Engineering, Medical University of BiałystokMateusz Cieśluk - Department of Microbiological and Nanobiomedical Engineering, Medical University of BiałystokAgnieszka Z. Wilczewska - Institute of Chemistry, University of Białystok, Białystok, PolandJan R. Dąbrowski - Department of Materials and Biomedical Engineering, Białystok University of TechnologyRobert Bucki - Department of Microbiological and Nanobiomedical Engineering, Medical University of BiałystokKarpiński TM, Szkaradkiewicz AK. Chlorhexidine – pharmacobiological activity and application. Eur Rev Med Pharmacol Sci. 2015; 19(7):1321–1326.Wood A, Payne D. The action of three antiseptics/disinfectants against enveloped and non-enveloped viruses. J Hosp Infect. 1998;38(4): 283–295.Fathilah AR, Himratul-Aznita WH, Fatheen AR, Suriani KR. The antifungal properties of chlorhexidine digluconate and cetylpyrinidinium chloride on oral Candida. J Dent. 2012;40(7):609–615.Kuyyakanond T, Quesnel LB. The mechanism of action of chlorhexidine. FEMS Microbiol Lett. 1992;100(1–3):211–215.Zorko M, Jerala R. Alexidine and chlorhexidine bind to lipopolysaccharide and lipoteichoic acid and prevent cell activation by antibiotics. J Antimicrob Chemother. 2008;62(4):730–737.Bonacorsi C, Raddi MS, Carlos IZ. Cytotoxicity of chlorhexidine digluconate to murine macrophages and its effect on hydrogen peroxide and nitric oxide induction. Braz J Med Biol Res. 2004;37(2):207–212.Mimoz O, Lucet JC, Kerforne T, et al. Skin antisepsis with chlorhexidine-alcohol versus povidone iodine-alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, twoby-two factorial trial. Lancet. 2015;386(10008):2069–2077.Coetzee E, Rode H, Kahn D. Pseudomonas aeruginosa burn wound infection in a dedicated paediatric burns unit. S Afr J Surg. 2013;51(2): 50–53.Varoni E, Tarce M, Lodi G, Carrassi A. Chlorhexidine (CHX) in dentistry: state of the art. Minerva Stomatol. 2012;61(9):399–419.Manikandan D, Balaji VR, Niazi TM, Rohini G, Karthikeyan B, Jesudoss P. Chlorhexidine varnish implemented treatment strategy for chronic periodontitis: a clinical and microbial study. J Pharm Bioallied Sci. 2016;8(Suppl 1):S133–S137.Edmiston CE Jr, Bruden B, Rucinski MC, Henen C, Graham MB, Lewis BL. Reducing the risk of surgical site infections: does chlorhexidine gluconate provide a risk reduction benefit? Am J Infect Control. 2013;41(5 Suppl):S49–S55.Miller LM, Loder JS, Hansbrough JF, Peterson HD, Monafo WW, Jordan MH. Patient tolerance study of topical chlorhexidine diphosphanilate: a new topical agent for burns. Burns. 1990;16(3):217–220.Supranoto SC, Slot DE, Addy M, Van der Weijden GA. The effect of chlorhexidine dentifrice or gel versus chlorhexidine mouthwash on plaque, gingivitis, bleeding and tooth discoloration: a systematic review. Int J Dent Hyg. 2015;13(2):83–92.Athanassiadis B, Abbott PV, Walsh LJ. The use of calcium hydroxide, antibiotics and biocides as antimicrobial medicaments in endodontics. Aust Dent J. 2007;52(1 Suppl):S64–S82.McDonnell G, Russell AD. Antiseptics and disinfectants: activity, action, and resistance. Clin Microbiol Rev. 1999;12(1):147–179.Brooks SE, Walczak MA, Hameed R, Coonan P. Chlorhexidine resistance in antibiotic-resistant bacteria isolated from the surfaces of dispensers of soap containing chlorhexidine. Infect Control Hosp Epidemiol. 2002;23(11):692–695.Bhardwaj P, Ziegler E, Palmer KL. Chlorhexidine induces vanAtype vancomycin resistance genes in enterococci. Antimicrob Agents Chemother. 2016;60(4):2209–2221.Liu Q, Zhao H, Han L, Shu W, Wu Q, Ni Y. Frequency of biocideresistant genes and susceptibility to chlorhexidine in high-level-mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MuHMRSA). Diagn Microbiol Infect Dis. 2015;82(4):278–283.Huh AJ, Kwon YJ. “Nanoantibiotics”: a new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era. J Control Release. 2011;156(2):128–145.Piktel E, Niemirowicz K, Wątek M, Wollny T, Deptuła P, Bucki R. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy. J Nanobiotechnology. 2016; 14(1):39.Niemirowicz K, Prokop I, Wilczewska AZ, et al. Magnetic nanoparticles enhance the anticancer activity of cathelicidin LL-37 peptide against colon cancer cells. Int J Nanomedicine. 2015;10:3843–3853.Niemirowicz K, Surel U, Wilczewska AZ, et al. Bactericidal activity and biocompatibility of ceragenin-coated magnetic nanoparticles. J Nanobiotechnology. 2015;13(1):32.Michalak G, Gluszek K, Piktel E, et al. Polymeric nanoparticles – a novel solution for delivery of antimicrobial agents. Studia Medyczne. 2016;32(1):56–62.Gu H, Ho PL, Tong E, Wang L, Xu B. Presenting vancomycin on nanoparticles to enhance antimicrobial activities. Nano Letters. 2003;3(9): 1261–1263.Niemirowicz K, Markiewicz KH, Wilczewska AZ, Car H. Magnetic nanoparticles as new diagnostic tools in medicine. Adv Med Sci. 2012;57(2):196–207.Niemirowicz K, Swiecicka I, Wilczewska AZ, et al. Growth arrest and rapid capture of select pathogens following magnetic nanoparticle treatment. Colloids Surf B Biointerfaces. 2015;131:29–38.Park H, Park HJ, Kim JA, et al. Inactivation of Pseudomonas aeruginosa PA01 biofilms by hyperthermia using superparamagnetic nanoparticles. J Microbiol Methods. 2011;84(1):41–45.Taylor E, Webster TJ. Reducing infections through nanotechnology and nanoparticles. Int J Nanomedicine. 2011;6:1463–1473.Niemirowicz K, Durnas´ B, Tokajuk G, et al. Magnetic nanoparticles as a drug delivery system that enhance fungicidal activity of polyene antibiotics. Nanomedicine. 2016;12(8):2395–2404.Massart R. Preparation of aqueous magnetic liquids in alkaline and acidic media. IEEE Transactions on Magnetics. 1981;17(2):1247–1248.Niemirowicz K, Swiecicka I, Wilczewska AZ, et al. Gold-functionalized magnetic nanoparticles restrict growth of Pseudomonas aeruginosa. Int J Nanomedicine. 2014;9:2217–2224.Misztalewska I, Wilczewska AZ, Wojtasik O, Markiewicz KH, Kuchlewski P, Majcher AM. New acetylacetone-polymer modified nanoparticles as magnetically separable complexing agents. RSC Advances. 2015;5(121):100281–100289.Meletiadis J, Mouton JW, Meis JF, et al. Comparison of spectrophotometric and visual readings of NCCLS method and evaluation of a colorimetric method based on reduction of a soluble tetrazolium salt, 2,3-bis [2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2Htetrazolium-hydroxide], for antifungal susceptibility testing of Aspergillus species. J Clin Microbiol. 2001;39(12):4256–4263.Sabaeifard P, Abdi-Ali A, Soudi MR, Dinarvand R. Optimization of tetrazolium salt assay for Pseudomonas aeruginosa biofilm using microtiter plate method. J Microbiol Methods. 2014;105:134–140.O’Toole GA. Microtiter dish biofilm formation assay. J Vis Exp. 2011;(47):pii 2437.Hussein-Al-Ali SH, El Zowalaty ME, Hussein MZ, Ismail M, Webster TJ. Synthesis, characterization, controlled release, and antibacterial studies of a novel streptomycin chitosan magnetic nanoantibiotic. Int J Nanomed. 2014;9:549–557.Niemirowicz K, Piktel E, Wilczewska AZ, et al. Core-shell magnetic nanoparticles display synergistic antibacterial effects against Pseudomonas aeruginosa and Staphylococcus aureus when combined with cathelicidin LL-37 or selected ceragenins. Int J Nanomedicine. 2016;11:5443–5455.Bucki R, Niemirowicz K, Wnorowska U, et al. Polyelectrolyte-mediated increase of biofilm mass formation. BMC Microbiol. 2015;15:117.Wnorowska U, Wątek M, Durnas´ B, et al. Extracellular DNA as an essential component and therapeutic target of microbial biofilm. Studia Medyczne. 2015;31(2):132–138.Nguyen TK, Duong HTT, Selvanayagam R, Boyer C, Barraud N. Iron oxide nanoparticle-mediated hyperthermia stimulates dispersal in bacterial biofilms and enhances antibiotic efficacy. Sci Rep. 2015;5:18385.Barrett-Bee K, Newboult L, Edwards S. The membrane destabilising action of the antibacterial agent chlorhexidine. FEMS Microbiol Lett. 1994;119(1–2):249–253.Audus KL, Tavakoli-Saberi MR, Zheng H, Boyce EN. Chlorhexidine effects on membrane lipid domains of human buccal epithelial cells. J Dent Res. 1992;71(6):1298–1303.Mantri SS, Mantri SP. The nano era in dentistry. J Nat Sci Biol Med. 2013;4(1):39–44.Abou Neel EA, Bozec L, Perez RA, Kim HW, Knowles JC. Nanotechnology in dentistry: prevention, diagnosis, and therapy. Int J Nanomedicine. 2015;10:6371–6394.Li F, Weir MD, Fouad AF, Xu HH. Effect of salivary pellicle on antibacterial activity of novel antibacterial dental adhesives using a dental plaque microcosm biofilm model. Dent Mater. 2014;30(2):182–191.Besinis A, De Peralta T, Handy RD. Inhibition of biofilm formation and antibacterial properties of a silver nano-coating on human dentine. Nanotoxicology. 2014;8(7):745–754.Siqueira JF, Sen BH. Fungi in endodontic infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97(5):632–641.Gomes C, Fidel S, Fidel R, de Moura Sarquis MI. Isolation and taxonomy of filamentous fungi in endodontic infections. J Endod. 2010; 36(4):626–629.O’Donnell LE, Millhouse E, Sherry L, et al. Polymicrobial Candida biofilms: friends and foe in the oral cavity. FEMS Yeast Res. 2015;15(7).Amenabar I, Poly S, Nuansing W, et al. Structural analysis and mapping of individual protein complexes by infrared nanospectroscopy. Nat Commun. 2013;4:2890.Shi YB, Liu L, Shao W, Wei T, Lin GM. Microcalorimetry studies of the antimicrobial actions of alkaloids. J Zhejiang Univ Sci B. 2015; 16(8):690–695.Miyake Y, Tsunoda T, Minagi S, Akagawa Y, Tsuru H, Suginaka H. Antifungal drugs affect adherence of Candida albicans to acrylic surfaces by changing the zeta-potential of fungal cells. FEMS Microbiol Lett. 1990;57(3):211–214.Sardi JC, Scorzoni L, Bernardi T, Fusco-Almeida AM, Mendes Giannini MJ. Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. J Med Microbiol. 2013;62(Pt 1):10–24.Balloni S, Locci P, Lumare A, Marinucci L. Cytotoxicity of three commercial mouthrinses on extracellular matrix metabolism and human gingival cell behaviour. Toxicol In Vitro. 2016;34:88–96.Poletaev A, Boura P. The immune system, natural autoantibodies and general homeostasis in health and disease. Hippokratia. 2011;15(4): 295–298.Wong DT, Cheung GS. Extension of bactericidal effect of sodium hypochlorite into dentinal tubules. J Endod. 2014;40(6):825–829.Peck BW, Workeneh B, Kadikoy H, Abdellatif A. Sodium hypochloriteinduced acute kidney injury. Saudi J Kidney Dis Transpl. 2014;25(2): 381–384.Cavaleiro E, Duarte AS, Esteves AC, et al. Novel linear polymers able to inhibit bacterial quorum sensing. Macromol Biosci. 2015;15(5): 647–656.Guégan S, Lanternier F, Rouzaud C, Dupin N, Lortholary O. Fungal skin and soft tissue infections. Curr Opin Infect Dis. 2016;29(2):124–130.Chen H, Shi Q, Qing Y, Yao YC, Cao YG. Cytotoxicity of modified nonequilibrium plasma with chlorhexidine digluconate on primary cultured human gingival fibroblasts. J Huazhong Univ Sci Technolog Med Sci. 2016;36(1):137–141.Wang B, Wei P, Wang X, Lou W. Controlled synthesis and sizedependent thermal conductivity of Fe3 O4 magnetic nanofluids. Dalton Trans. 2012;41(3):896–899.127833784