Antibacterial and Antibiofilm Efficacy of Copper-Doped Phosphate Glass on Pathogenic Bacteria.

This study aimed to investigate the antibacterial [minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC)] and antibiofilm activity [log10 colony forming unit/mL (CFU/mL) and biofilm disruption] of copper-doped phosphate glass (CDPG) against Streptococcus oralis, Enterococcus faecalis, Lactobacillus casei, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. METHODS: the antibacterial activity was determined using microbroth dilution and time-kill assay. The antibiofilm activity was investigated using crystal violet and confocal laser scanning microscopy. Bacteria growing in absence of CDPG were used as controls. RESULTS: the MIC was ≥125 mg of CPDG/mL; the log10 CFU/mL reduction ranged from 2.66-3.14 to 6.23-9.65 after 4 and 24 h respectively. Generally, no growth was observed after 24 h of treatment with CDPG; the MBC was 250 mg/mL for L. casei and S. oralis while 500 mg/mL for the rest of the bacteria. The highest and lowest antibiofilm activity was observed against S. oralis and E. coli respectively. Three patterns of complete biofilm disruption were seen: (i) large areas with E. fecalis and S. oralis, (ii) medium-size pockets with S. aureus and P. aeruginosa, or (iii) small areas with E. coli and L. casei. CONCLUSION: CDPG can be potentially used as an antibacterial and an antibiofilm agent against oral biofilm-forming bacteria.

Superfast Set, Strong and Less Degradable Mineral Trioxide Aggregate Cement.

PURPOSE: Despite the good sealing ability and biocompatibility of mineral trioxide aggregate (MTA), its slow setting, high degradation, and weakness limit its use in surgical endodontics and high stress-bearing areas. This study aimed to develop two new liquids to control these drawbacks. They were prepared from calcium chloride, fumed silica, and hydroxyapatite or calcium phosphate and coded "H" and "P," respectively. METHODS: Portland cement, Grey ProRoot® MTA, and white ProRoot MTA were mixed with distilled water (control) or liquid "H" or "P." The pH, setting time, degradation rate, leachant/precipitate' composition, compressive strength, and morphology were assessed. RESULTS: Both liquids maintained MTA's high alkalinity and reduced the setting time by 1-2 orders of magnitude. Both liquids, H in particular, significantly reduced the degradation rate of Grey ProRoot and White ProRoot MTA®. Calcite has been identified as the main phase of the leachant or precipitate formed during the cement's degradation. Calcium hydroxide or hydroxyapatite was also identified with Grey ProRoot MTA mixed with H liquid. These liquids also significantly increased the compressive strength with no statistical differences between them; this was associated with the production of dense, consolidated structures. CONCLUSIONS: The modified MTA could be used in surgical endodontics and high stress-bearing areas.

Demineralization-remineralization dynamics in teeth and bone.

Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form unique hybrid biological tissues, for example, enamel, dentin, cementum, and bone. Understanding the process of mineral deposition is important for the development of treatments for mineralization-related diseases and also for the innovation and development of scaffolds. This review provides a thorough overview of the up-to-date information on the theories describing the possible mechanisms and the factors implicated as agonists and antagonists of mineralization. Then, the role of calcium and phosphate ions in the maintenance of teeth and bone health is described. Throughout the life, teeth and bone are at risk of demineralization, with particular emphasis on teeth, due to their anatomical arrangement and location. Teeth are exposed to food, drink, and the microbiota of the mouth; therefore, they have developed a high resistance to localized demineralization that is unmatched by bone. The mechanisms by which demineralization-remineralization process occurs in both teeth and bone and the new therapies/technologies that reverse demineralization or boost remineralization are also scrupulously discussed. Technologies discussed include composites with nano- and micron-sized inorganic minerals that can mimic mechanical properties of the tooth and bone in addition to promoting more natural repair of surrounding tissues. Turning these new technologies to products and practices would improve health care worldwide.

Nanotechnology in dentistry: prevention, diagnosis, and therapy.

Nanotechnology has rapidly expanded into all areas of science; it offers significant alternative ways to solve scientific and medical questions and problems. In dentistry, nanotechnology has been exploited in the development of restorative materials with some significant success. This review discusses nanointerfaces that could compromise the longevity of dental restorations, and how nanotechnolgy has been employed to modify them for providing long-term successful restorations. It also focuses on some challenging areas in dentistry, eg, oral biofilm and cancers, and how nanotechnology overcomes these challenges. The recent advances in nanodentistry and innovations in oral health-related diagnostic, preventive, and therapeutic methods required to maintain and obtain perfect oral health, have been discussed. The recent advances in nanotechnology could hold promise in bringing a paradigm shift in dental field. Although there are numerous complex therapies being developed to treat many diseases, their clinical use requires careful consideration of the expense of synthesis and implementation.

The future perspectives of natural materials for pulmonary drug delivery and lung tissue engineering.

INTRODUCTION: Search for new, functional biomaterials that can be used to synergistically deliver a drug, enhance its adsorption and stimulate the post-injury recovery of tissue function, is one of the priorities in biomedicine. Currently used materials for drug delivery fail to satisfy one or more of these functionalities, thus they have limited potential and new classes of materials are urgently needed. AREAS COVERED: Natural materials, due to their origin, physical and chemical structure can potentially fulfill these requirements and there is already strong evidence of their usefulness in drug delivery. They are increasingly utilized in various therapeutic applications due to the obvious advantages over synthetic materials. Particularly in pulmonary drug delivery, there have been limitations in the use of synthetic materials such as polymers and lipids, leading to an increase in the use of natural and protein-based materials such as silk, keratin, elastin and collagen. Literature search in each specialized field, namely, silk, keratin and collagen was conducted, and the benefits of each material for future application in pulmonary drug delivery are highlighted. EXPERT OPINION: The natural materials discussed in this review have been well established in their use for other applications, yet further studies are required in the application of pulmonary drug delivery. The properties exhibited by these natural materials seem positive for their application in lung tissue engineering, which may allow for more extensive testing for validation of pulmonary drug delivery systems.

Tissue engineering in dentistry.

OBJECTIVES: of this review is to inform practitioners with the most updated information on tissue engineering and its potential applications in dentistry. DATA: The authors used "PUBMED" to find relevant literature written in English and published from the beginning of tissue engineering until today. A combination of keywords was used as the search terms e.g., "tissue engineering", "approaches", "strategies" "dentistry", "dental stem cells", "dentino-pulp complex", "guided tissue regeneration", "whole tooth", "TMJ", "condyle", "salivary glands", and "oral mucosa". SOURCES: Abstracts and full text articles were used to identify causes of craniofacial tissue loss, different approaches for craniofacial reconstructions, how the tissue engineering emerges, different strategies of tissue engineering, biomaterials employed for this purpose, the major attempts to engineer different dental structures, finally challenges and future of tissue engineering in dentistry. STUDY SELECTION: Only those articles that dealt with the tissue engineering in dentistry were selected. CONCLUSIONS: There have been a recent surge in guided tissue engineering methods to manage periodontal diseases beyond the traditional approaches. However, the predictable reconstruction of the innate organisation and function of whole teeth as well as their periodontal structures remains challenging. Despite some limited progress and minor successes, there remain distinct and important challenges in the development of reproducible and clinically safe approaches for oral tissue repair and regeneration. Clearly, there is a convincing body of evidence which confirms the need for this type of treatment, and public health data worldwide indicates a more than adequate patient resource. The future of these therapies involving more biological approaches and the use of dental tissue stem cells is promising and advancing. Also there may be a significant interest of their application and wider potential to treat disorders beyond the craniofacial region. CLINICAL SIGNIFICANCE: Considering the interests of the patients who could possibly be helped by applying stem cell-based therapies should be carefully assessed against current ethical concerns regarding the moral status of the early embryo.

Biological performance of titania containing phosphate-based glasses for bone tissue engineering applications.

The interplay between glass chemistry, structure, degradation kinetics, and biological activity provides flexibility for the development of scaffolds with highly specific cellular response. The aim of this study was therefore to investigate the role of titania inclusion into the phosphate-based glass on its ability to stimulate osteoblast-like human osteosarcoma (HOS) cells to adhere, proliferate and differentiate. In depth morphological and biochemical characterisation was performed on HOS cells cultured on the surface of glass discs. Cell proliferation was also studied in the presence of the glass extract. Cell differentiation, through osteoblast phenotype genes, alkaline phosphatase (ALP) activity and osteocalcin production, was carried out using normal or osteogenic media. Both Thermanox® and titania free glass were used as controls. The data demonstrated that titania inclusion provides desired cytocompatible surface that supported initial cell attachment, sustained viability, and increased cell proliferation similar or significantly higher than Thermanox®. The modified glasses regulated osteoblastic cell differentiation as detected by osteoblast phenotype gene transcription and upregulated ALP and osteocalcin expression. Using osteogenic media had no significant effect on ALP activity and osteocalcin expression. Therefore, titania modified phosphate glasses may have future use as bone tissue engineering scaffolds.

Effect of increasing titanium dioxide content on bulk and surface properties of phosphate-based glasses.

There is an ingoing need for more effective and less costly bone substitute materials. In a previous study, addition of titanium dioxide (TiO2) up to 5 mol.% was shown to be effective in controlling glass degradation, and this was reflected in enhanced gene expression and bone-forming capacity of phosphate-based glasses. In the current study, incorporation of the maximum possible amount of TiO2 has been attempted in order to further improve the biological response of these glasses. This report describes the physical, surface properties and short-term response of an osteoblast cell line (MG63) on phosphate glasses doped with the maximum possible TiO2 content. The results showed that a maximum of 15 mol.% TiO2 can be incorporated into the ternary formulations while maintaining their amorphous nature; such incorporation was associated with a significant increase in density and glass transition temperature. On crystallization, X-ray diffraction analysis showed the presence of TiP2O7 and NaCa(PO3)3 as the main phases for all TiO2-containing glasses, while beta-(CaP2O6) was only detected for 10 and 15 mol.% TiO2 glasses. The degradation rate, however, was significantly reduced by an order of magnitude with incorporation of 10 and 15 mol.% TiO2, and this was reflected in the released ions. This change in the bulk properties, produced with TiO2 incorporation, was also associated with a significant change in the hydrophilicity and surface reactivity of these glasses. Even though the addition of TiO2 reduced the hydrophilicity and the surface free energy of these glasses compared to TiO2 free composition, TiO2-containing glasses still have a significantly reactive surface layer compared to Thermanox. Generally glasses with 5-15 mol.% TiO2 supported MG63 cell growth and maintained high cell viability for up to 7 days culture, which is comparable to Thermanox. Based on the results obtained from this study, TiO2-containing phosphate glasses are promising substrates for bone tissue engineering applications.

Processing, characterisation, and biocompatibility of zinc modified metaphosphate based glasses for biomedical applications.

Bulk and structural properties of zinc oxide (0 up to 20 mol%) containing phosphate glasses, developed for biomedical applications, were investigated throughout this study using differential thermal analysis (DTA), differential scanning calorimetry, X-ray powder diffraction and 31P and 23Na MAS NMR. Surface wettability and MG63 viability were also considered for surface characterisation of these glasses. The results indicated that incorporation of zinc oxide as a dopant into phosphate glasses produced a significant increase in density; however, the thermal properties presented in glass transition, and melting temperatures were reduced. NaZn(PO3)3 was detected in the X-Ray Powder Diffraction Analysis (XRD) trace of zinc containing glasses, and the proportion of this phase increased with increasing zinc oxide content. NaCa(PO3)3 as a second main phase and CaP2O6 in minor amounts were also detected. The 31P and 23Na MAS NMR results suggested that the relative abundances of the Q1 and Q2 phosphorus sites, and the local sodium environment were unaffected as CaO was replaced by ZnO in this system. The replacement of CaO with ZnO did seem to have the effect of increasing the local disorder of the Q2 metaphosphate chains, but less so for the Q1 chain-terminating sites which were already relatively disordered due to the proximity of modifying cations. Glasses with zinc oxide less than 5 mol% showed higher surface wettability, while those with 5 up to 20 mol% showed comparable wettability as zinc oxide free glasses. Regardless of the high hydrophilicity and surface reactivity of these zinc oxide containing glasses, they had lower biocompatibility, in particular 10-20 mol% ZnO, compared to both zinc free glasses and Thermanox. This may be associated with the release of significant amount of Zn2+ enough to be toxic to MG63.

In vitro bioactivity and gene expression by cells cultured on titanium dioxide doped phosphate-based glasses.

In our previous study, glasses with 50 P(2)O(5)-(20-15) Na(2)O-30 CaO-(0-5 mol%) TiO(2) have been prepared by the conventional melt-quenching process. MG63 cell proliferation, gene expression, in vivo biocompatibility, and bioactivity of these glasses is the concern of this study. The results showed that addition of TiO(2) in small amounts up to 5 mol% enhanced the biocompatibility of these glasses. The cell metabolic activity was conspicuous, on 3 and 5 mol% TiO(2) compositions in particular, with no significant difference from Thermanox control over a period of 21 days. The findings from the gene expression study showed that, at day 1 and on 5 mol% TiO(2) glass, core binding protein factor alpha 1 (Cbfa1) and alkaline phosphatase (ALP) showed significantly lower transcription level; however, collagen type I alpha subunit I (COLIAI) and Osteonectin (Sparc) showed no significant differences compared to the control. At day 7, all these genes transcription levels were not significantly different form the control, but at day 14, they were significantly higher than the control. Moreover, there were no significant differences detected in these genes on both 3 and 5 mol% TiO(2) glasses up to 7 days. At day 14; however, 5 mol% TiO(2) glasses showed significantly higher level than 3 mol% TiO(2) composition. This was also correlated by the presence of new bone tissue at the bone-particles interface for 5 mol% TiO(2) composition after 5 weeks of implantation in rat calvarium. Regardless of this favourable cell response and gene up-regulation, these glasses showed no evidence of apatite layer formation after 14 days incubation in SBF.