New Ceramic Multi-Unit Dental Abutments with an Antimicrobial Glassy Coating.

The choice of suitable materials and new designs in oral implantology and the subsequent enhancement of the characteristics of the dental implant developed is an important research topic with wide scope. The present work aims to develop a new multifunctional zirconia-ceria/alumina (Ce-TZP/Al2O3) composite with an antimicrobial glass-based coating to be used in multi-unit abutments compatible with commercially available Ti implants for peri-implantitis prevention. An airbrush spraying technique was effectively applied to coat the sintered ceramic composite starting from a glass powder suspension. This deposition technique was appropriate for obtaining continuous antimicrobial glass-based coatings with homogenous thickness (~35 µm) on ceramic dental implant components. The dental implant systems with the antimicrobial glassy coating were subjected to a mechanical integrity test following ISO 14801 to determine their long-term stability. The tested implant-coating structure seems to be stable under in vitro conditions with ultimate applied forces exceeding the maximum physiological occlusal loading force. This paper also presents a pilot clinical case report that shows peri-implant tissue around the mechanically stable glass coating with no signs of inflammation 1 year after implant insertion. This result is a preliminary probe of the durability and biological tolerance of the glassy material by the gingiva, as well as the antimicrobial effect on the peri-implant microbiota displayed by the coating.

Broad virus inactivation using inorganic micro/nano-particulate materials.

Inorganic materials can provide a set of tools to decontaminate solid, liquid or air containing viral particles. The use of disinfectants can be limited or not practical in scenarios where continuous cleaning is not feasible. Physicochemical differences between viruses raise the need for effective formulations for all kind of viruses. In the present work we describe two types of antimicrobial inorganic materials: i) a novel soda-lime glass (G3), and ii) kaolin containing metals nanoparticles (Ag or CuO), as materials to disable virus infectivity. Strong antiviral properties can be observed in G3 glass, and kaolin-containing nanoparticle materials showing a reduction of viral infectivity close to 99%. in the first 10 â€‹min of contact of vesicular stomatitis virus (VSV). A potent virucidal activity is also present in G3 and kaolin containing Ag or CuO nanoparticles against all kinds of viruses tested, reducing more than 99% the amount of HSV-1, Adenovirus, VSV, Influenza virus and SARS-CoV-2 exposed to them. Virucidal properties could be explained by a direct interaction of materials with viruses as well as inactivation by the presence of virucidal elements in the material lixiviates. Kaolin-based materials guarantee a controlled release of active nanoparticles with antiviral activity. Current coronavirus crisis highlights the need for new strategies to remove viruses from contaminated areas. We propose these low-cost inorganic materials as useful disinfecting antivirals in the actual or future pandemic threats.

Adding Two Antimicrobial Glasses to an Endodontic Sealer to Prevent Bacterial Root Canal Reinfection: An In Vivo Pilot Study in Dogs.

Current endodontic procedures continue to be unsuccessful for completely removing pathogens present inside the root canal system, which can lead to recurrent infections. In this study, we aimed to assess the antimicrobial capacity and tissue response of two inorganic bactericidal additives incorporated into a paste root canal sealer on contaminated root dentin in vivo. An experimental study was performed in 30 teeth of five Beagle dogs. After inducing microbiological contamination, root canal systems were treated by randomly incorporating one of two antimicrobial additives into a commercial epoxy-amine resin sealer (AH Plus), i.e., G3T glass-ceramic (n = 10) and ZnO-enriched glass (n = 10); 10 samples were randomized as a control group. After having sacrificed the animals, microbiological, radiological, and histological analyses were performed, which were complemented with an in vitro bactericidal test and characterization by field emission scanning electron microscopy. The tested groups demonstrated a non-significant microbiological reduction in the postmortem periapical index values between the control group and the bactericidal glass-ceramic group (p = 0.885), and between the control group and the ZnO-enriched glass group (p = 0.169). The histological results showed low values of inflammatory infiltrate, and a healing pattern characterized by fibrosis in 44.4% of the G3T glass-ceramic and 60.0% of ZnO-enriched glass. Bactericidal glassy additives incorporated in this root canal sealer are safe and effective in bacterial reduction.

No genome-wide DNA methylation changes found associated with medium-term reduced graphene oxide exposure in human lung epithelial cells.

The presence of nanomaterials in our everyday life is ever increasing, and so too are concerns about the possible health consequences of exposure to them. While evidence of their biological activity is growing, there is still scant knowledge of the epigenetic mechanisms that could be at play in these processes. Moreover, the great variability in the chemical and physical structures of these compounds handicaps the study of their possible health risks. Here we have synthesized reduced graphene oxide (rGO) through the thermal exfoliation/reduction of graphite oxide, and characterized the resulting material. We have then made use of Illumina's MethylationEPIC arrays and bisulphite pyrosequencing to analyse the genome-wide and global DNA methylation dynamics associated with the medium-term exposure of human lung epithelial cells to rGO at concentrations of 1 and 10 µg/mL. The results show no genome-wide or global DNA methylation changes associated with either condition. Our observations thus suggest that medium-term rGO exposure does not have significant effects on the DNA methylation patterns of human lung epithelial cells.

Epigenetics in cancer therapy and nanomedicine.

The emergence of nanotechnology applied to medicine has revolutionized the treatment of human cancer. As in the case of classic drugs for the treatment of cancer, epigenetic drugs have evolved in terms of their specificity and efficiency, especially because of the possibility of using more effective transport and delivery systems. The use of nanoparticles (NPs) in oncology management offers promising advantages in terms of the efficacy of cancer treatments, but it is still unclear how these NPs may be affecting the epigenome such that safe routine use is ensured. In this work, we summarize the importance of the epigenetic alterations identified in human cancer, which have led to the appearance of biomarkers or epigenetic drugs in precision medicine, and we describe the transport and release systems of the epigenetic drugs that have been developed to date.

Bactericidal ZnO glass-filled thermoplastic polyurethane and polydimethyl siloxane composites to inhibit biofilm-associated infections.

This study investigates a novel approach to controlling biofilms of the most frequent pathogens implicated in the etiology of biomaterials-associated infections. New bactericidal filler based on a non-toxic glass, belonging to B2O3-SiO2-Al2O3-Na2O-ZnO system, was used to formulate composites of the most widely used polymers in biomedical applications [i.e. thermoplastic polyurethane (TPU) and polydimethyl siloxane (PDMS)], with varying percentage by weight of the bactericidal glass (5, 15, 25, 35, 50%). Glass-filled polymer composites show dramatically restricted bacterial colonisation and biofilm formation. They exhibit time- and dose-dependent killing, with maximal action at 5 days. The highest activity was found against S.epidermidis biofilm (99% of reduction), one of the most common cause of nosocomial infections. The tensile properties of the obtained glass-filled composites are comparable with the literature data concerning polymeric biomaterials for medical implants and devices. In addition, all the materials presented in this research, revealed an excellent biocompatibility. This was disclosed by cell viability values above 70%, none alteration on erythrocyte membrane or cell functionality in contact with materials (haemolytic index 0-2%), and absence of interferences in blood coagulation (intrinsic, extrinsic and final pathways).

Current state-of-the-art and future perspectives of the three main modern implant-dentistry concerns: Aesthetic requirements, mechanical properties, and peri-implantitis prevention.

The idea of permanent tooth replacement goes back to the year 2000 BC at least, when carved bamboo pegs were used to replace missing teeth in ancient China. The phenomenon of osseointegration, however, was not verified until the mid-1960s, when Branemark discovered that titanium could integrate to bone. Since then, the osseointegration capacity of implants has been profoundly investigated and implants as such have evolved enormously in all possible aspects, from material selection and processing to specific surface engineering, among many others. This review article, in particular, focuses on dental implants and aims to introduce the main concerns involved in modern dentistry, concentrating especially on the importance of finding an effective way to prevent peri-implantitis. In this sense, strategies such as shifting from metal to ceramic implant components and applying novel antimicrobial antibiotic-free coatings seem to be taking the lead. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

DNA methylation changes in human lung epithelia cells exposed to multi-walled carbon nanotubes.

Humans are increasingly exposed to nanoparticles and, although many of their physiological effects have been described, the molecular mechanisms underlying them are still largely unknown. The present study aimed to determine the possible role of certain epigenetic mechanisms in the cellular response of human lung epithelial cells that are triggered by long-term exposure to titanium dioxide nanoparticles (TiO2NPs) and multi-walled carbon nanotubes (MWCNTs). The results showed that exposure to TiO2NPs had only minor effects on genome-wide DNA methylation. However, we identified 755 CpG sites showing consistent DNA hypomethylation in cells exposed to MWCNTs. These sites were mainly located at low density CpG regions and enhancers, and very frequently on the X chromosome. Our results thus suggest that long-term MWCNT exposure may have important effects on the epigenome.

Effect of the Medium Composition on the Zn2+ Lixiviation and the Antifouling Properties of a Glass with a High ZnO Content.

The dissolution of an antimicrobial ZnO-glass in the form of powder and in the form of sintered pellets were studied in water, artificial seawater, biological complex media such as common bacterial/yeast growth media (Luria Bertani (LB), yeast extract, tryptone), and human serum. It has been established that the media containing amino acids and proteins produce a high lixiviation of Zn2+ from the glass due to the ability of zinc and zinc oxide to react with amino acids and proteins to form complex organic compounds. The process of Zn2+ lixiviation from the glass network has been studied by X-ray photoelectron spectroscopy (XPS). From these results we can state that the process of lixiviation of Zn2+ from the glass network is similar to the one observed in sodalime glasses, where Na⁺ is lixiviated to the media first and the fraction of Zn that acts as modifiers (~2/3) is lixiviated in second place. After the subsequent collapse of the outer surface glass layer (about 200-300 nm thick layer) the dissolution process starts again. Antifouling properties against different bacteria (S. epidermidis, S. aureus, P. aeruginosa, E. coli, and M. lutea) have also been established for the glass pellets.

Performance of a New Al2O3/Ce-TZP Ceramic Nanocomposite Dental Implant: A Pilot Study in Dogs.

Although titanium remains as the prevalent material in dental implant manufacturing new zirconia-based materials that overcome the major drawbacks of the standard 3Y-yttria partially-stabilized zirconia (Y-TZP) are now emerging. In this study, a new ceramic nanocomposite made of alumina and ceria-stabilized TZP (ZCe-A) has been used to produce dental implants with the mechanic and topographic characteristics of a pilot implant design to evaluate bone and soft tissue integration in a dog model (n = 5). Histological cross-section analysis of the implanted ceramic fixations (n = 15) showed not only perfect biocompatibility, but also a high rate of osseous integration (defined as the percentage of bone to implant contact) and soft tissue attachment. This clinical success, in combination with the superior mechanical properties achieved by this Al2O3/Ce-TZP nanocomposite, may place this material as an improved alternative of traditional 3Y-TZP dental implants.

Histological response of soda-lime glass-ceramic bactericidal rods implanted in the jaws of beagle dogs.

Bacterial and fungal infections remain a major clinical challenge. Implant infections very often require complicated revision procedures that are troublesome to patients and costly to the healthcare system. Innovative approaches to tackle infections are urgently needed. We investigated the histological response of novel free P2O5 glass-ceramic rods implanted in the jaws of beagle dogs. Due to the particular percolated morphology of this glass-ceramic, the dissolution of the rods in the animal body environment and the immature bone formation during the fourth months of implantation maintained the integrity of the glass-ceramic rod. No clinical signs of inflammation took place in any of the beagle dogs during the four months of implantation. This new glass-ceramic biomaterial with inherent bactericidal and fungicidal properties can be considered as an appealing candidate for bone tissue engineering.

Evaluation in a Dog Model of Three Antimicrobial Glassy Coatings: Prevention of Bone Loss around Implants and Microbial Assessments.

OBJECTIVES: The aim of the present study is to evaluate, in a ligature-induced peri-implantitis model, the efficacy of three antimicrobial glassy coatings in the prevention of biofilm formation, intrasulcular bacterial growth and the resulting peri-implant bone loss. METHODS: Mandibular premolars were bilaterally extracted from five beagle dogs. Four dental implants were inserted on each hemiarch. Eight weeks after, one control zirconia abutment and three with different bactericidal coatings (G1n-Ag, ZnO35, G3) were connected. After a plaque control period, bacterial accumulation was allowed and biofilm formation on abutments was observed by Scanning Electron Microscopy (SEM). Peri-implantitis was induced by cotton ligatures. Microbial samples and peri-implant crestal bone levels of all implant sites were obtained before, during and after the breakdown period. RESULTS: During experimental induce peri-implantitis: colony forming units counts from intrasulcular microbial samples at implants with G1n-Ag coated abutment remained close to the basal inoculum; G3 and ZnO35 coatings showed similar low counts; and anaerobic bacterias counts at control abutments exhibited a logarithmic increase by more than 2. Bone loss during passive breakdown period was no statistically significant. Additional bone loss occurred during ligature-induce breakdown: 0.71 (SD 0.48) at G3 coating, 0.57 (SD 0.36) at ZnO35 coating, 0.74 (SD 0.47) at G1n-Ag coating, and 1.29 (SD 0.45) at control abutments; and statistically significant differences (p<0.001) were found. The lowest bone loss at the end of the experiment was exhibited by implants dressing G3 coated abutments (mean 2.1; SD 0.42). SIGNIFICANCE: Antimicrobial glassy coatings could be a useful tool to ward off, diminish or delay peri-implantitis progression.

Antibacterial and Antifungal Activity of ZnO Containing Glasses.

A new family of non-toxic biocides based on low melting point (1250°C) transparent glasses with high content of ZnO (15-40wt%) belonging to the miscibility region of the B2O3-SiO2-Na2O-ZnO system has been developed. These glasses have shown an excellent biocide activity (logarithmic reduction >3) against Gram- (E. coli), Gram+ (S. aureus) and yeast (C. krusei); they are chemically stable in different media (distilled water, sea-like water, LB and DMEN media) as well as biocompatible. The cytotoxicity was evaluated by the Neutral Red Uptake using NIH-3T3 (mouse embryonic fibroblast cells) and the cell viability was >80%. These new glasses can be considered in several and important applications in the field of inorganic non-toxic biocide agents such as medical implants, surgical equipment, protective apparels in hospitals, water purifications systems, food packaging, food storages or textiles.

Calcium and zinc containing bactericidal glass coatings for biomedical metallic substrates.

The present work presents new bactericidal coatings, based on two families of non-toxic, antimicrobial glasses belonging to B2O3-SiO2-Na2O-ZnO and SiO2-Na2O-Al2O3-CaO-B2O3 systems. Free of cracking, single layer direct coatings on different biomedical metallic substrates (titanium alloy, Nb, Ta, and stainless steel) have been developed. Thermal expansion mismatch was adjusted by changing glass composition of the glass type, as well as the firing atmosphere (air or Ar) according to the biomedical metallic substrates. Formation of bubbles in some of the glassy coatings has been rationalized considering the reactions that take place at the different metal/coating interfaces. All the obtained coatings were proven to be strongly antibacterial versus Escherichia coli (>4 log).

A new biocompatible and antibacterial phosphate free glass-ceramic for medical applications.

In the attempt to find valid alternatives to classic antibiotics and in view of current limitations in the efficacy of antimicrobial-coated or loaded biomaterials, this work is focused on the development of a new glass-ceramic with antibacterial performance together with safe biocompatibility. This bactericidal glass-ceramic composed of combeite and nepheline crystals in a residual glassy matrix has been obtained using an antimicrobial soda-lime glass as a precursor. Its inhibitory effects on bacterial growth and biofilm formation were proved against five biofilm-producing reference strains. The biocompatibility tests by using mesenchymal stem cells derived from human bone indicate an excellent biocompatibility.

Bone loss at implant with titanium abutments coated by soda lime glass containing silver nanoparticles: a histological study in the dog.

The aim of the present study was to evaluate bone loss at implants connected to abutments coated with a soda-lime glass containing silver nanoparticles, subjected to experimental peri-implantitis. Also the aging and erosion of the coating in mouth was studied. Five beagle dogs were used in the experiments. Three implants were placed in each mandible quadrant: in 2 of them, Glass/n-Ag coated abutments were connected to implant platform, 1 was covered with a Ti-mechanized abutment. Experimental peri-implantitis was induced in all implants after the submarginal placement of cotton ligatures, and three months after animals were euthanatized. Thickness and morphology of coating was studied in abutment cross-sections by SEM. Histology and histo-morphometric studies were carried on in undecalfied ground slides. After the induced peri-implantitis: 1.The abutment coating shown losing of thickness and cracking. 2. The histometry showed a significant less bone loss in the implants with glass/n-Ag coated abutments. A more symmetric cone of bone resorption was observed in the coated group. There were no significant differences in the peri-implantitis histological characteristics between both groups of implants. Within the limits of this in-vivo study, it could be affirmed that abutments coated with biocide soda-lime-glass-silver nanoparticles can reduce bone loss in experimental peri-implantitis. This achievement makes this coating a suggestive material to control peri-implantitis development and progression.

Nanocomposites of silver nanoparticles embedded in glass nanofibres obtained by laser spinning.

Nanocomposites made of non-woven glass fibres with diameters ranging from tens of nanometers up to several micrometers, containing silver nanoparticles, were successfully fabricated by the laser spinning technique. Pellets of a soda-lime silicate glass containing silver nanoparticles with varying concentrations (5 and 10 wt%) were used as a precursor. The process followed to obtain the silver nanofibres did not agglomerate significantly the metallic nanoparticles, and the average particle size is still lower than 50 nm. This is the first time that glass nanofibres containing silver nanoparticles have been obtained following a process different from electrospinning of a sol-gel, thus avoiding the limitations of this method and opening a new route to composite nanomaterials. Antibacterial efficiency of the nanosilver glass fibres, tested against one of the most common gram negative bacteria, was greater than 99.99% compared to the glass fibres free of silver. The silver nanoparticles are well-dispersed not only on the surface but are also embedded into the uniform nanofibres, which leads to a long lasting durable antimicrobial effect. All these novel characteristics will potentially open up a whole new range of applications.

Inhibitory effect on in vitro Streptococcus oralis biofilm of a soda-lime glass containing silver nanoparticles coating on titanium alloy.

This paper reports the effect of soda-lime-glass-nAg coating on the viability of an in vitro biofilm of Streptococcus oralis. Three strains (ATCC 35037 and two clinical isolates from periodontitis patients) were grown on coated with glass, glass containing silver nanoparticles, and uncoated titanium alloy disks. Two different methods were used to quantify biofilm formation abilities: crystal violet staining and determination of viable counts. The influence of the surface morphology on the cell attachment was studied. The surface morphology was characterized by scanning electron microscopy (SEM) and using a profilometer. SEM was also used to study the formation and the development of biofilm on the coated and uncoated disks. At least a >99.7% inocula reduction of biofilm respect to titanium disks and also to glass coated disks was observed in the glass-nAg coated disks for all the studied strains. A quantitative evaluation of the release of silver was conducted in vitro to test whether and to what extend the biocidal agent (silver) could leach from the coating. These findings suggest that the biofilm formation of S. oralis strains is highly inhibited by the glass-nAg and may be useful for materials which require durable antibacterial effect on their surfaces, as it is the case of dental implants.

Ceramic/metal biocidal nanocomposites for bone-related applications.

Hydroxyapatite/silver nanocomposites have been designed and synthesized as an engineering material for biomedical applications. The hydroxyapatite matrix was synthesized by a sol-gel method and, subsequently, the Ag nanoparticles were deposited by heterogeneous precipitation followed by two different reduction routes: thermal or chemical. Both sets were studied and compared and, in all cases, the metal nanoparticles appear perfectly isolated and attached to the surface of the hydroxyapatite. The average metal particle size is below 10 nm, allowing an important contact surface between silver and the microorganisms. The antimicrobial behavior against common bacteria showed a high effectiveness, well above the commercial level, as well as against yeast, in the case of the chemically reduced sample. Due to the nanocomposite microstructure, only a negligible portion of metal was released to the lixiviated liquid after the biocide tests, minimizing the risk of toxicity. These nanocomposites offer a solution to the infections on the surface of implants, one of the main problems in reaching a suitable level of osseointegration.