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      Effect of pH-sensitive nanoparticles on inhibiting oral biofilms

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          Abstract

          Dental caries is a biofilm-related preventable infectious disease caused by interactions between the oral bacteria and the host’s dietary sugars. As the microenvironments in cariogenic biofilms are often acidic, pH-sensitive drug delivery systems have become innovative materials for dental caries prevention in recent years. In the present study, poly(DMAEMA-co-HEMA) was used as a pH-sensitive carrier to synthesize a chlorhexidine (CHX)-loaded nanomaterial (p(DH)@CHX). In vitro, p(DH)@CHX exhibited good pH sensitivity and a sustained and high CHX release rate in the acidic environment. It also exhibited lower cytotoxicity against human oral keratinocytes (HOKs) compared to free CHX. Besides, compared with free CHX, p(DH)@CHX showed the same antibacterial effects on S. mutans biofilms. In addition, it had no effect on eradicating healthy saliva-derived biofilm, while free CHX exhibited an inhibitory effect. Furthermore, the 16s rDNA sequencing results showed that p(DH)@CHX had the potential to alter oral microbiota composition and possibly reduce caries risk. In conclusion, the present study presents an alternative option to design an intelligent material to prevent and treat dental caries.

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          The role of bacteria in the caries process: ecological perspectives.

          Dental biofilms produce acids from carbohydrates that result in caries. According to the extended caries ecological hypothesis, the caries process consists of 3 reversible stages. The microflora on clinically sound enamel surfaces contains mainly non-mutans streptococci and Actinomyces, in which acidification is mild and infrequent. This is compatible with equilibrium of the demineralization/remineralization balance or shifts the mineral balance toward net mineral gain (dynamic stability stage). When sugar is supplied frequently, acidification becomes moderate and frequent. This may enhance the acidogenicity and acidurance of the non-mutans bacteria adaptively. In addition, more aciduric strains, such as 'low-pH' non-mutans streptococci, may increase selectively. These microbial acid-induced adaptation and selection processes may, over time, shift the demineralization/remineralization balance toward net mineral loss, leading to initiation/progression of dental caries (acidogenic stage). Under severe and prolonged acidic conditions, more aciduric bacteria become dominant through acid-induced selection by temporary acid-impairment and acid-inhibition of growth (aciduric stage). At this stage, mutans streptococci and lactobacilli as well as aciduric strains of non-mutans streptococci, Actinomyces, bifidobacteria, and yeasts may become dominant. Many acidogenic and aciduric bacteria are involved in caries. Environmental acidification is the main determinant of the phenotypic and genotypic changes that occur in the microflora during caries.
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            Microbial ecology of dental plaque and its significance in health and disease.

            P.D. Marsh (1994)
            Dental plaque forms naturally on teeth and is of benefit to the host by helping to prevent colonization by exogenous species. The bacterial composition of plaque remains relatively stable despite regular exposure to minor environmental perturbations. This stability (microbial homeostasis) is due in part to a dynamic balance of both synergistic and antagonistic microbial interactions. However, homeostasis can break down, leading to shifts in the balance of the microflora, thereby predisposing sites to disease. For example, the frequent exposure of plaque to low pH leads to inhibition of acid-sensitive species and the selection of organisms with an aciduric physiology, such as mutans streptococci and lactobacilli. Similarly, plaque accumulation around the gingival margin leads to an inflammatory host response and an increased flow of gingival crevicular fluid. The subgingival microflora shifts from being mainly Gram-positive to being comprised of increased levels of obligately anaerobic, asaccharolytic Gram-negative organisms. It is proposed that disease can be prevented or treated not only by targeting the putative pathogens but also by interfering with the processes that drive the breakdown in homeostasis. Thus, the rate of acid production following sugar intake could be reduced by fluoride, alternative sweeteners, and low concentrations of antimicrobial agents, while oxygenating or redox agents could raise the Eh of periodontal pockets and prevent the growth and metabolism of obligately anaerobic species. These views have been incorporated into a modified hypothesis (the "ecological plaque hypothesis") to explain the relationship between the plaque microflora and the host in health and disease, and to identify new strategies for disease prevention.
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              Biology, immunology, and cariogenicity of Streptococcus mutans.

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                Author and article information

                Journal
                Drug Deliv
                Drug Deliv
                Drug Delivery
                Taylor & Francis
                1071-7544
                1521-0464
                14 February 2022
                2022
                14 February 2022
                : 29
                : 1
                : 561-573
                Affiliations
                [a ]State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University , Chengdu, China
                [b ]Department of Operative Dentistry and Endodontics, West China School of Stomatology, Sichuan University , Chengdu, China
                [c ]Department of Oral Pathology, West China School of Stomatology, Sichuan University , Chengdu, China
                Author notes
                CONTACT Lei Cheng chenglei@ 123456scu.edu.cn
                Xian Peng pengx@ 123456scu.edu.cn State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University , Chengdu 610041, China
                Author information
                https://orcid.org/0000-0002-2762-4740
                Article
                2037788
                10.1080/10717544.2022.2037788
                8856036
                35156501
                c916321b-91fb-4db4-b886-b5940971f131
                © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 8, Tables: 2, Pages: 13, Words: 8818
                Categories
                Research Article
                Research Article

                Pharmacology & Pharmaceutical medicine
                ph-sensitive drug delivery system,nanocarrier,chlorhexidine,dental caries,s. mutans,intelligent material

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