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      Dental Composites with Calcium / Strontium Phosphates and Polylysine

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          Abstract

          Purpose

          This study developed light cured dental composites with added monocalcium phosphate monohydrate (MCPM), tristrontium phosphate (TSrP) and antimicrobial polylysine (PLS). The aim was to produce composites that have enhanced water sorption induced expansion, can promote apatite precipitation and release polylysine.

          Materials and Methods

          Experimental composite formulations consisted of light activated dimethacrylate monomers combined with 80 wt% powder. The powder phase contained a dental glass with and without PLS (2.5 wt%) and/or reactive phosphate fillers (15 wt% TSrP and 10 wt% MCPM). The commercial composite, Z250, was used as a control. Monomer conversion and calculated polymerization shrinkage were assessed using FTIR. Subsequent mass or volume changes in water versus simulated body fluid (SBF) were quantified using gravimetric studies. These were used, along with Raman and SEM, to assess apatite precipitation on the composite surface. PLS release was determined using UV spectroscopy. Furthermore, biaxial flexural strengths after 24 hours of SBF immersion were obtained.

          Results

          Monomer conversion of the composites decreased upon the addition of phosphate fillers (from 76 to 64%) but was always higher than that of Z250 (54%). Phosphate addition increased water sorption induced expansion from 2 to 4% helping to balance the calculated polymerization shrinkage of ~ 3.4%. Phosphate addition promoted apatite precipitation from SBF. Polylysine increased the apatite layer thickness from ~ 10 to 20 μm after 4 weeks. The novel composites showed a burst release of PLS (3.7%) followed by diffusion-controlled release irrespective of phosphate addition. PLS and phosphates decreased strength from 154 MPa on average by 17% and 18%, respectively. All formulations, however, had greater strength than the ISO 4049 requirement of > 80 MPa.

          Conclusion

          The addition of MCPM with TSrP promoted hygroscopic expansion, and apatite formation. These properties are expected to help compensate polymerization shrinkage and help remineralize demineralized dentin. Polylysine can be released from the composites at early time. This may kill residual bacteria.

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          Most cited references46

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          In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis.

          A comparative in vitro cytotoxicity study with different water-soluble, cationic macromolecules which have been described as gene delivery systems was performed. Cytotoxicity in L929 mouse fibroblasts was monitored using the MTT assay and the release of the cytosolic enzyme lactate dehydrogenase (LDH). Microscopic observations were carried out as indicators for cell viability. Furthermore, hemolysis of erythrocytes was quantified spectrophotometrically. To determine the nature of cell death induced by the polycations, the nuclear morphology after DAPI staining and the inhibition of the toxic effects by the caspase inhibitor zVAD.fmk were investigated. All assays yielded comparable results and allowed the following ranking of the polymers with regard to cytotoxicity: Poly(ethylenimine)=poly(L-lysine)>poly(diallyl-dimethyl-ammonium chloride)>diethylaminoethyl-dextran>poly(vinyl pyridinium bromide)>Starburst dendrimer>cationized albumin>native albumin. The magnitude of the cytotoxic effects of all polymers were found to be time- and concentration dependent. The molecular weight as well as the cationic charge density of the polycations were confirmed as key parameters for the interaction with the cell membranes and consequently, the cell damage. Evaluating the nature of cell death induced by poly(ethylenimine), we did not detect any indication for apoptosis suggesting that the polymer induced a necrotic cell reaction. Cell nuclei retained their size, chromatin was homogenously distributed and cell membranes lost their integrity very rapidly at an early stage. Furthermore, the broad spectrum caspase inhibitor zVAD.fmk did not inhibit poly(ethylenimine)-induced cell damage. Insights into the structure-toxicity relationship are necessary to optimize the cytotoxicity and biocompatibility of non-viral gene delivery systems.
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            Hygroscopic and hydrolytic effects in dental polymer networks.

            The objective of this manuscript is to outline the factors associated with hygroscopic and hydrolytic effects in dental polymer networks, and to review the literature generated over the past thirty years or more in this area. Information was gathered from nearly 90 published articles or abstracts appearing in the dental and polymer literature. Studies were predominantly identified through a search of the PubMED database. Studies were included that provided direct evidence for the uptake of solvent by a polymer network and its subsequent physical or chemical effect, or the loss of molecular species into solvents. An attempt was made to select articles that spanned the timeframe from approximately 1970 to today to ensure that most of the classic literature as well as the latest information was included. Dental polymer networks have been shown to be susceptible to hygroscopic and hydrolytic effects to varying extents dependent upon their chemistry and structure. The importance of these effects on the clinical performance of polymer restoratives is largely unknown, though numerous investigators have alluded to the potential for reduced service lives. While the physical and mechanical properties of these materials may be significantly altered by the effects of solvent uptake and component elution, what may constitute the greatest concern is the short-term release of unreacted components and the long-term elution of degradation products in the oral cavity, both of which should be strongly considered during restorative material development.
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              Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems.

              The advancement in material design and engineering has led to the rapid development of new materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literature published after the 1990s. The release kinetics of selected drug compounds from various material systems is discussed in case studies. Recent progress in the mathematical models based on different transport mechanisms is highlighted. This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drug delivery matrices. Understanding the structure-function relationship of the material system is key to the successful design of a delivery system for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                11 October 2016
                2016
                : 11
                : 10
                : e0164653
                Affiliations
                [1 ]Department of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, London, United Kingdom
                [2 ]Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS, Lahore, Pakistan
                [3 ]Department of Restorative Dentistry, Unit of Prosthodontics, UCL Eastman Dental Institute, London, United Kingdom
                Institute of Materials Science, GERMANY
                Author notes

                Competing Interests: The work is covered by the following licensed patent families: Formulations and composites with reactive fillers (US8252851 B2, EP2066703B1, US20100069469, WO2008037991A1), and Formulations and materials with cationic polymers (PCT/GB2014/052349, WO2015015212 A1, EP3027164A1, US20160184190). This may be considered a conflict of interest as in the future the corresponding author (Anne Young) may receive royalties when a commercial product is produced. This author currently has funding from NIHR and is working with Schottlander Dental Company to optimize a similar product to those in the publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                • Conceptualization: PP WX HP AY.

                • Formal analysis: PP AY.

                • Funding acquisition: PP EZ AY.

                • Investigation: PP SL EZ.

                • Methodology: PP WX AY.

                • Project administration: HP AY.

                • Supervision: PP HP AY.

                • Validation: PP AY.

                • Visualization: PP HP AY.

                • Writing – original draft: PP HP AY.

                Article
                PONE-D-16-16357
                10.1371/journal.pone.0164653
                5058497
                27727330
                d6425f83-1bdf-4909-9896-f8de2b5cfbbc
                © 2016 Panpisut et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 April 2016
                : 28 September 2016
                Page count
                Figures: 6, Tables: 2, Pages: 19
                Funding
                Funded by: Royal Thai Government (Ministry of Sciences and Technology)
                Award Recipient :
                Funded by: National Institute for Health Research (Invention for Innovation (i4i))
                Award ID: II-LB-0214-2002
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000266, Engineering and Physical Sciences Research Council;
                Award ID: EPI/I022341/1
                Award Recipient :
                Funded by: Welcome Trust
                Award ID: Wtissf 3: Institutional Strategic Support Fund (ISSF) Third Tranche
                Award Recipient :
                The Royal Thai Government (Ministry of Sciences and Technology) (PP), National Institute for Health Research (Invention for Innovation (i4i, http://www.nihr.ac.uk/funding/invention-for-innovation.htm)); Optimisation and commercial manufacture of tooth-coloured composite dental-fillings with added poly-antimicrobial (PAM) and remineralising calcium phosphate (CaP), II-LB-0214-2002) (WX), UK EPSRC (Engineering and Physical Sciences Research Council, https://www.epsrc.ac.uk) (EPI/I02234/1)(WX); and Welcome Trust (Wtissf 3: Institutional Strategic Support Fund (Issf) Third Tranche, www.wellcome.ac.uk/Funding/WTP057769.htm) (WX) have provided financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Compounds
                Phosphates
                Physical Sciences
                Chemistry
                Chemical Reactions
                Polymerization
                Physical Sciences
                Chemistry
                Polymer Chemistry
                Polymerization
                Physical Sciences
                Materials Science
                Materials by Structure
                Composite Materials
                Physical Sciences
                Chemistry
                Chemical Reactions
                Chemical Precipitation
                Physical Sciences
                Chemistry
                Physical Chemistry
                Sorption
                Physical Sciences
                Chemistry
                Polymer Chemistry
                Macromolecules
                Polymers
                Physical Sciences
                Materials Science
                Materials by Structure
                Polymers
                Physical Sciences
                Materials Science
                Materials by Structure
                Amorphous Solids
                Glass
                Physical Sciences
                Chemistry
                Chemical Elements
                Strontium
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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