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With the rising demand for medical implants and the dominance of implant-associated failures including infections, extensive research has been prompted into the development of novel biomaterials that can offer desirable characteristics. This study develops and evaluates new titanium-based alloys containing gallium additions with the aim of offering beneficial antibacterial properties while having a reduced stiffness level to minimise the effect of stress shielding when in contact with bone. The focus is on the microstructure, mechanical properties, antimicrobial activity, and cytocompatibility to inform the suitability of the designed alloys as biometals. Novel Ti-33Nb-xGa alloys (x = 3, 5 wt%) were produced via casting followed by homogenisation treatment, where all results were compared to the currently employed alloy Ti-6Al-4V. Optical microscopy, scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) results depicted a single beta (ß) phase microstructure in both Ga-containing alloys, where Ti-33Nb-5Ga was also dominated by dendritic alpha (α) phase grains in a ß-phase matrix. EDS analysis indicated that the α-phase dendrites in Ti-33Nb-5Ga were enriched with titanium, while the ß-phase was richer in niobium and gallium elements. Mechanical properties were measured using nanoindentation and microhardness methods, where the Young's modulus for Ti-33Nb-3Ga and Ti-33Nb-5Ga was found to be 75.4 ± 2.4 and 67.2 ± 1.6 GPa, respectively, a significant reduction of 37% and 44% with respect to Ti-6Al-4V. This reduction helps address the disproportionate Young's modulus between titanium implant components and cortical bone. Importantly, both alloys successfully achieved superior antimicrobial properties against Gram-negative P. aeruginosa and Gram-positive S. aureus bacteria. Antibacterial efficacy was noted at up to 90 ± 5% for the 3 wt% alloy and 95 ± 3% for the 5 wt% alloy. These findings signify a substantial enhancement of the antimicrobial performance when compared to Ti-6Al-4V which exhibited very small rates (up to 6.3 ± 1.5%). No cytotoxicity was observed in hGF cell lines over 24 h. Cell morphology and cytoskeleton distribution appeared to depict typical morphology with a prominent nucleus, elongated fibroblastic spindle-shaped morphology, and F-actin filamentous stress fibres in a well-defined structure of parallel bundles along the cellular axis. The developed alloys in this work have shown very promising results and are suggested to be further examined towards the use of orthopaedic implant components.
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The urgency to address skeletal abnormalities and diseases through innovative approaches has led to a significant interdisciplinary convergence of engineering, 3D printing, and design in developing individualised bioceramic bioscaffolds. This review explores into the recent advancements and future trajectory of non-antibiotic antibacterial bioceramics in bone tissue engineering, an importance given the escalating challenges of orthopaedic infections, antibiotic resistance, and emergent pathogens. Initially, the review provides an in-depth exploration of the complex interactions among bacteria, immune cells, and bioceramics in clinical contexts, highlighting the multifaceted nature of infection dynamics, including protein adsorption, immunological responses, bacterial adherence, and endotoxin release. Then, focus on the next-generation bioceramics designed to offer multifunctionality, especially in delivering antibacterial properties independent of traditional antibiotics. A key highlight of this study is the exploration of smart antibacterial bioceramics, marking a revolutionary stride in medical implant technology. The review also aims to guide the ongoing development and clinical adoption of bioceramic materials, focusing on their dual capabilities in promoting bone regeneration and exhibiting antibacterial properties. These next-generation bioceramics represent a paradigm shift in medical implant technology, offering multifunctional benefits that transcend traditional approaches.
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Developing novel antibacterial strategies has become an urgent requisite to overcome the increasing pervasiveness of antimicrobial-resistant bacteria and the advent of biofilms. Aggregation-induced emission-based photosensitizers (AIE PSs) are promising candidates due to their unique photodynamic and photothermal properties. Bioengineering structure-inherent AIE PSs for developing thin film coatings is still an unexplored area in the field of nanoscience. We have adopted a synergistic approach combining plasma technology and AIE PS-based photodynamic therapy to develop coatings that can eradicate bacterial infections. Here, we loaded AIE PSs within biomimetic bacterium-like particles derived from a probiotic strain, Lactobacillus fermentum. These hybrid conjugates are then immobilized on polyoxazoline-coated substrates to develop a bioinspired coating to fight against implant-associated infections. These coatings could selectively kill Gram-positive and Gram-negative bacteria, but not damage mammalian cells. The mechanistic studies revealed that the coatings can generate reactive oxygen species that can rupture the bacterial cell membranes. The mRNA gene expression of proinflammatory cytokines confirmed that they can modulate infection-related immune responses. Thus, this nature-inspired design has opened a new avenue for the fabrication of a next-generation antibacterial coating to reduce infections and associated burdens.
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Fotoquimioterapia , Fármacos Fotossensibilizantes , Animais , Fármacos Fotossensibilizantes/química , Antibacterianos/química , Biomimética , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Bactérias , Complicações Pós-Operatórias , MamíferosRESUMO
In the quest to curtail the spread of healthcare-associated infections, this work showcases the fabrication of a cutting-edge antibacterial textile coating armoured with aggregation-induced emission photosensitisers (AIE PS) to prevent bacterial colonisation on textiles. The adopted methodology includes a multi-step process using plasma polymerisation and subsequent integration of AIE PS on their surface. The antibacterial effectiveness of the coating was tested against Pseudomonas aeruginosa and Staphylococcus aureus after light irradiation for 1 h. Furthermore, antibacterial mechanistic studies revealed their ability to generate reactive oxygen species that can damage bacterial cell membrane integrity. The results of this investigation can be used to develop ground-breaking explanations for infection deterrence, principally in situations where hospital fabrics play a critical part in the transmission of diseases. The antibacterial coating for textiles developed in this study holds great promise as an efficient strategy to promote public health and reduce the danger of bacterial diseases through regular contact with fabrics.
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Infecção Hospitalar , Infecções Estafilocócicas , Humanos , Antibacterianos/farmacologia , Staphylococcus aureus , Têxteis , Atenção à SaúdeRESUMO
Nanomaterials in the food industry are used as food additives, and the main function of these food additives is to improve food qualities including texture, flavor, color, consistency, preservation, and nutrient bioavailability. This review aims to provide an overview of the distribution, fate, and environmental and health impacts of food additive nanomaterials in soil and aquatic ecosystems. Some of the major nanomaterials in food additives include titanium dioxide, silver, gold, silicon dioxide, iron oxide, and zinc oxide. Ingestion of food products containing food additive nanomaterials via dietary intake is considered to be one of the major pathways of human exposure to nanomaterials. Food additive nanomaterials reach the terrestrial and aquatic environments directly through the disposal of food wastes in landfills and the application of food waste-derived soil amendments. A significant amount of ingested food additive nanomaterials (> 90 %) is excreted, and these nanomaterials are not efficiently removed in the wastewater system, thereby reaching the environment indirectly through the disposal of recycled water and sewage sludge in agricultural land. Food additive nanomaterials undergo various transformation and reaction processes, such as adsorption, aggregation-sedimentation, desorption, degradation, dissolution, and bio-mediated reactions in the environment. These processes significantly impact the transport and bioavailability of nanomaterials as well as their behaviour and fate in the environment. These nanomaterials are toxic to soil and aquatic organisms, and reach the food chain through plant uptake and animal transfer. The environmental and health risks of food additive nanomaterials can be overcome by eliminating their emission through recycled water and sewage sludge.
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Nanoestruturas , Eliminação de Resíduos , Poluentes do Solo , Animais , Humanos , Solo , Esgotos , Ecossistema , Alimentos , Poluentes do Solo/análise , Meio Ambiente , Aditivos Alimentares , ÁguaRESUMO
Antimicrobial strategies for musculoskeletal infections are typically first developed with in vitro models. The In Vitro Section of the 2023 Orthopedic Research Society Musculoskeletal Infection international consensus meeting (ICM) probed our state of knowledge of in vitro systems with respect to bacteria and biofilm phenotype, standards, in vitro activity, and the ability to predict in vivo efficacy. A subset of ICM delegates performed systematic reviews on 15 questions and made recommendations and assessment of the level of evidence that were then voted on by 72 ICM delegates. Here, we report recommendations and rationale from the reviews and the results of the internet vote. Only two questions received a ≥90% consensus vote, emphasizing the disparate approaches and lack of established consensus for in vitro modeling and interpretation of results. Comments on knowledge gaps and the need for further research on these critical MSKI questions are included.
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Biofilmes , ConsensoRESUMO
The threat of infection during implant placement surgery remains a considerable burden for millions of patients worldwide. To combat this threat, clinicians employ a range of anti-infective strategies and practices. One of the most common interventions is the use of prophylactic antibiotic treatment during implant placement surgery. However, these practices can be detrimental by promoting the resilience of biofilm-forming bacteria and enabling them to persist throughout treatment and re-emerge later, causing a life-threatening infection. Thus, it is of the utmost importance to elucidate the events occurring during the initial stages of bacterial surface attachment and determine whether any biological processes may be targeted to improve surgical outcomes. Using gene expression analysis, we identified a cellular mechanism of S. aureus which modifies its cell surface charge following attachment to a medical grade titanium surface. We determined the upregulation of two systems involved in the d-alanylation of teichoic acids and the lysylation of phosphatidylglycerol. We supported these molecular findings by utilizing synchrotron-sourced attenuated total reflection Fourier-transform infrared microspectroscopy to analyze the biomolecular properties of the S. aureus cell surface following attachment. As a direct consequence, S. aureus quickly becomes substantially more tolerant to the positively charged vancomycin, but not the negatively charged cefazolin. The present study can assist clinicians in rationally selecting the most potent antibiotic in prophylaxis treatments. Furthermore, it highlights a cellular process that could potentially be targeted by novel technologies and strategies to improve the outcome of antibiotic prophylaxis during implant placement surgery. STATEMENT OF SIGNIFICANCE: The antibiotic tolerance of bacteria in biofilm is a well-established phenomenon. However, the physiological adaptations employed by Staphylococcus aureus to increase its antibiotic tolerance during the early stages of surface attachment are poorly understood. Using multiple techniques, including gene expression analysis and synchrotron-sourced Fourier-transform infrared microspectroscopy, we generated insights into the physiological response of S. aureus following attachment to a medical grade titanium surface. We showed that this phenotypic transition enables S. aureus to better tolerate the positively charged vancomycin, but not the negatively charged cefazolin. These findings shed light on the antibiotic tolerance mechanisms employed by S. aureus to survive prophylactically administered antibiotics and can help clinicians to protect patients from infections.
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Antibacterianos , Infecções Estafilocócicas , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus/fisiologia , Vancomicina/farmacologia , Cefazolina/metabolismo , Titânio/farmacologia , Infecções Estafilocócicas/prevenção & controle , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
Naturally occurring and synthetic nanostructured surfaces have been widely reported to resist microbial colonization. The majority of these studies have shown that both bacterial and fungal cells are killed upon contact and subsequent surface adhesion to such surfaces. This occurs because the presence of high-aspect-ratio structures can initiate a self-driven mechanical rupture of microbial cells during the surface adsorption process. While this technology has received a large amount of scientific and medical interest, one important question still remains: what factors drive microbial death on the surface? In this work, the interplay between microbial-surface adhesion, cell elasticity, cell membrane rupture forces, and cell lysis at the microbial-nanostructure biointerface during adsorptive processes was assessed using a combination of live confocal laser scanning microscopy, scanning electron microscopy, in situ amplitude atomic force microscopy, and single-cell force spectroscopy. Specifically, the adsorptive behavior and nanomechanical properties of live Gram-negative (Pseudomonas aeruginosa) and Gram-positive (methicillin-resistant Staphylococcus aureus) bacterial cells, as well as the fungal species Candida albicans and Cryptococcus neoformans, were assessed on unmodified and nanostructured titanium surfaces. Unmodified titanium and titanium surfaces with nanostructures were used as model substrates for investigation. For all microbial species, cell elasticity, rupture force, maximum cell-surface adhesion force, the work of adhesion, and the cell-surface tether behavior were compared to the relative cell death observed for each surface examined. For cells with a lower elastic modulus, lower force to rupture through the cell, and higher work of adhesion, the surfaces had a higher antimicrobial activity, supporting the proposed biocidal mode of action for nanostructured surfaces. This study provides direct quantification of the differences observed in the efficacy of nanostructured antimicrobial surface as a function of microbial species indicating that a universal, antimicrobial surface architecture may be hard to achieve.
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Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Nanoestruturas , Adesão Celular , Titânio/farmacologia , Titânio/química , Aderência Bacteriana , Nanoestruturas/química , Anti-Infecciosos/farmacologia , ElasticidadeRESUMO
With the rising demand for implantable orthopaedic medical devices and the dominance of device-associated infections, extensive research into the development of novel materials has been prompted. Among these, new-generation titanium alloys with biocompatible elements and improved stiffness levels have received much attention. Furthermore, the development of titanium-based materials that can impart antibacterial function has demonstrated promising results, where gallium has exhibited superior antimicrobial action. This has been evidenced by the addition of gallium to various biomaterials including titanium alloys. Therefore, this paper aims to review the antibacterial activity of gallium when incorporated into biomedical materials, with a focus on titanium-based alloys. First, discussion into the development of new-generation Ti alloys that possess biocompatible elements and reduced Young's moduli is presented. This includes a brief review of the influence of alloying elements, processing techniques and the resulting biocompatibilities of the materials found in the literature. The antibacterial effect of gallium added to various materials, including bioglasses, liquid metals, and bioceramics, is then reviewed and discussed. Finally, a key focus is given to the incorporation of gallium into titanium systems for which the inherent mechanical, biocompatible, and antibacterial effects are reviewed and discussed in more detail, leading to suggestions and directions for further research in this area.
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Bacterial colonization of implantable biomaterials is an ever-pervasive threat that causes devastating infections, yet continues to elude resolution. In the present study, we report how a rationally designed antibacterial surface containing sharp nanospikes can enhance the susceptibility of pathogenic bacteria to antibiotics used in prophylactic procedures. We show that Staphylococcus aureus, once adhered to a titanium surface, changes its cell-surface charge to increase its tolerance to vancomycin. However, if the Ti surface is modified to bear sharp nanospikes, the activity of vancomycin is rejuvenated, leading to increased bacterial cell death through synergistic activity. Analysis of differential gene expression provided evidence of a set of genes involved with the modification of cell surface charge. Synchrotron-sourced attenuated Fourier-transform infrared microspectroscopy (ATR-FTIR), together with multivariate analysis, was utilized to further elucidate the biochemical changes of S. aureus adhered to nanospikes. By inhibiting the ability of the pathogen to reduce its net negative charge, the nanoengineered surface renders S. aureus more susceptible to positively charged antimicrobials such as vancomycin. This finding highlights the opportunity to enhance the potency of prophylactic antibiotic treatments during implant placement surgery by employing devices having surfaces modified with spike-like nanostructures.
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Infecções Estafilocócicas , Vancomicina , Humanos , Vancomicina/farmacologia , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Próteses e ImplantesRESUMO
The challenge of wound healing, particularly in patients with comorbidities such as diabetes, is intensified by wound infection and the accelerating problem of bacterial resistance to current remedies such as antibiotics and silver. One promising approach harnesses the bioactive and antibacterial compound C-phycocyanin from the microalga Spirulina maxima. However, the current processes of extracting this compound and developing coatings are unsustainable and difficult to achieve. To circumvent these obstacles, a novel, sustainable argon atmospheric plasma jet (Ar-APJ) technology that transforms S. maxima biomass into bioactive coatings is presented. This Ar-APJ can selectively disrupt the cell walls of S. maxima, converting them into bioactive ultrathin coatings, which are found to be durable under aqueous conditions. The findings demonstrate that Ar-APJ-transformed bioactive coatings show better antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, these coatings exhibit compatibility with macrophages, induce an anti-inflammatory response by reducing interleukin 6 production, and promote cell migration in keratinocytes. This study offers an innovative, single-step, sustainable technology for transforming microalgae into bioactive coatings. The approach reported here has immense potential for the generation of bioactive coatings for combating wound infections and may offer a significant advance in wound care research and application.
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Bone tissue plays a crucial role in protecting internal organs and providing structural support and locomotion of the body. Treatment of hard tissue defects and medical conditions due to physical injuries, genetic disorders, aging, metabolic syndromes, and infections is more often a complex and drawn out process. Presently, dealing with hard-tissue-based clinical problems is still mostly conducted via surgical interventions. However, advances in nanotechnology over the last decades have led to shifting trends in clinical practice toward noninvasive and microinvasive methods. In this review article, recent advances in the development of nanoscale platforms for bone tissue engineering have been reviewed and critically discussed to provide a comprehensive understanding of the advantages and disadvantages of noninvasive and microinvasive methods for treating medical conditions related to hard tissue regeneration and repair.
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Nanotecnologia , Engenharia Tecidual , Engenharia Tecidual/métodos , Osso e Ossos/cirurgia , Sistemas de Liberação de Medicamentos , CicatrizaçãoRESUMO
The proliferation of drug resistance in microbial pathogens poses a significant threat to human health. Hence, treatment measures are essential to surmount this growing problem. In this context, liquid metal nanoparticles are promising. Gallium, a post-transition metal notable for being a liquid at physiological temperature, has drawn attention for its distinctive properties, high antimicrobial efficacy, and low toxicity. Moreover, gallium nanoparticles demonstrate anti-inflammatory properties in immune cells. Gallium can alloy with other metals and be prepared in various composites to modify and tailor its characteristics and functionality. More importantly, the bactericidal mechanism of gallium liquid metal could sidestep the threat of emerging drug resistance mechanisms. Building on this rationale, gallium-based liquid metal nanoparticles can enable impactful and innovative strategic pathways in the battle against antimicrobial resistance. This review outlines the characteristics of gallium-based liquid metals at the nanoscale and their corresponding antimicrobial mechanisms to provide a comprehensive yet succinct overview of their current antimicrobial applications. In addition, challenges and opportunities that require further research efforts have been identified and discussed.
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Anti-Infecciosos , Gálio , Nanopartículas Metálicas , Humanos , Gálio/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologiaRESUMO
Shell wastes pose environmental and financial burdens to the shellfish industry. Utilizing these undervalued shells for commercial chitin production could minimize their adverse impacts while maximizing economic value. Shell chitin conventionally produced through harsh chemical processes is environmentally unfriendly and infeasible for recovering compatible proteins and minerals for value-added products. However, we recently developed a microwave-intensified biorefinery that efficiently produced chitin, proteins/peptides, and minerals from lobster shells. Lobster minerals have a calcium-rich composition and biologically originated calcium is more biofunctional for use as a functional, dietary, or nutraceutical ingredient in many commercial products. This has suggested a further investigation of lobster minerals for commercial applications. In this study, the nutritional attributes, functional properties, nutraceutical effects, and cytotoxicity of lobster minerals were analyzed using in vitro simulated gastrointestinal digestion combined with growing bone (MG-63), skin (HaCaT), and macrophage (THP-1) cells. The calcium from the lobster minerals was found to be comparable to that of a commercial calcium supplement (CCS, 139 vs. 148 mg/g). In addition, beef incorporated with lobster minerals (2%, w/w) retained water better than that of casein and commercial calcium lactate (CCL, 21.1 vs. 15.1 and 13.3%), and the lobster mineral had a considerably higher oil binding capacity than its rivals (casein and CCL, 2.5 vs. 1.5 and 1.0 mL/g). Notably, the lobster mineral and its calcium were far more soluble than the CCS (98.4 vs. 18.6% for the products and 64.0 vs. 8.5% for their calcium) while the in vitro bioavailability of lobster calcium was 5.9-fold higher compared to that of the commercial product (11.95 vs. 1.99%). Furthermore, supplementing lobster minerals in media at ratios of 15%, 25%, and 35% (v/v) when growing cells did not induce any detectable changes in cell morphology and apoptosis. However, it had significant effects on cell growth and proliferation. The responses of cells after three days of culture supplemented with the lobster minerals, compared to the CCS supplementation, were significantly better with the bone cells (MG-63) and competitively quick with the skin cells (HaCaT). The cell growth reached 49.9-61.6% for the MG-63 and 42.9-53.4% for the HaCaT. Furthermore, the MG-63 and HaCaT cells proliferated considerably after seven days of incubation, reaching 100.3% for MG-63 and 115.9% for HaCaT with a lobster mineral supplementation of 15%. Macrophages (THP-1 cells) treated for 24 h with lobster minerals at concentrations of 1.24-2.89 mg/mL had no detectable changes in cell morphology while their viability was over 82.2%, far above the cytotoxicity threshold (<70%). All these results indicate that lobster minerals could be used as a source of functional or nutraceutical calcium for commercial products.
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Cálcio , Nephropidae , Animais , Bovinos , Cálcio/metabolismo , Nephropidae/metabolismo , Caseínas/metabolismo , Disponibilidade Biológica , Solubilidade , Minerais , Quitina/metabolismoRESUMO
Hydrogels have been widely used to entrap biomolecules for various biocatalytic reactions. However, solute diffusion in these matrices to initiate such reactions can be a very slow process. Conventional mixing remains a challenge as it can cause irreversible distortion or fragmentation of the hydrogel itself. To overcome the diffusion-limit, a shear-stress-mediated platform named the portable vortex-fluidic device (P-VFD) is developed. P-VFD is a portable platform which consists of two main components, (i) a plasma oxazoline-coated polyvinyl chloride (POx-PVC) film with polyacrylamide and alginate (PAAm/Alg-Ca2+) tough hydrogel covalently bound to its surface and (ii) a reactor tube (L × D: 90 mm × 20 mm) where the aforementioned POx-PVC film could be readily inserted for reactions. Through a spotting machine, the PAAm/Alg-Ca2+ hydrogel can be readily printed on a POx-PVC film in an array pattern and up to 25.4 J/m2 adhesion energy can be achieved. The hydrogel arrays on the film not only offer a strong matrix for entrapping biomolecules such as streptavidin-horseradish peroxidase but are also shear stress-tolerant in the reactor tube, enabling a >6-fold increase in its reaction rate after adding tetramethylbenzidine, relative to incubation. Through using the tough hydrogel and its stably bonded substrate, this portable platform effectively overcomes the diffusion-limit and achieves fast assay detection without causing appreciable hydrogel array deformation or dislocation on the substrate film.
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Metals tend to supercool-that is, they freeze at temperatures below their melting points. In general, supercooling is less favorable when liquids are in contact with nucleation sites such as rough surfaces. Interestingly, bulk gallium (Ga) can significantly supercool, even when it is in contact with heterogeneous surfaces that could provide nucleation sites. We hypothesized that the native oxide on Ga provides an atomically smooth interface that prevents Ga from directly contacting surfaces, and thereby promotes supercooling. Although many metals form surface oxides, Ga is a convenient metal for studying supercooling because its melting point of 29.8°C is near room temperature. Using differential scanning calorimetry (DSC), we show that freezing of Ga with the oxide occurs at a lower temperature (-15.6 ± 3.5°C) than without the oxide (6.9 ± 2.0°C when the oxide is removed by HCl). We also demonstrate that the oxide enhances supercooling via macroscopic observations of freezing. These findings explain why Ga supercools and have implications for emerging applications of Ga that rely on it staying in the liquid state.
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In this study, a eutectic gallium-indium (EGaIn) alloy and graphene nanoplatelets (GnPs) were employed as reinforcements for a comonomer vinyl ester (cVE) resin at different weight fractions up to 2% via a direct polymerization process. First, the effect of EGaIn on the curing kinetics of cVE was evaluated. The thermal and mechanical properties, and the fracture toughness of two types of cVE composites consisting of EGaIn and GnPs were then studied. The results showed that sub-micron sized EGaIn (≤1 wt.%) could promote the curing reaction of cVE without changing the curing mechanism. However, with further increases in EGaIn loading between 1 and 2 wt.%, the curing reaction rate tends to decrease. Both EGaIn and GnPs showed a significant enhancement in strengthening and toughening the cVE matrix with the presence of filler loading up to 1 wt.%. EGaIn was more effective than GnPs in promoting the flexural and impact strength. An increase of up to 50% and 32% were recorded for these mechanical properties, when EGaln was used, as compared to 46%, and 18% for GnPs, respectively. In contrast, the GnPs/cVE composites exhibited a greater improvement in the fracture toughness and fracture energy by up to 50% and 56% in comparison with those of the EGaIn/cVE ones by up to 32% and 39%, respectively. Furthermore, the stiffness of both the EgaIn/cVE and GnPs/cVE composites showed a significant improvement with an increase of up to 1.76 and 1.83 times in the normalized storage modulus, respectively, while the glass transition temperature (Tg) values remained relatively constant. This work highlights the potential of EGaIn being employed as a filler in creating high-performance thermoset composites, which facilitates its widening applications in many structural and engineering fields, where both higher toughness and stiffness are required.
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HYPOTHESIS: Titanium and its alloys are commonly used implant materials. Once inserted into the body, the interface of the biomaterials is the most likely site for the development of implant-associated infections. Imparting the titanium substrate with high-aspect-ratio nanostructures, which can be uniformly achieved using hydrothermal etching, enables a mechanical contact-killing (mechanoresponsive) mechanism of bacterial and fungal cells. Interaction between cells and the surface shows cellular inactivation via a physical mechanism meaning that careful engineering of the interface is needed to optimse the technology. This mechanism of action is only effective towards surface adsorbed microbes, thus any cells not directly in contact with the substrate will survive and limit the antimicrobial efficacy of the titanium nanostructures. Therefore, we propose that a dual-action mechanoresponsive and chemical-surface approach must be utilised to improve antimicrobial activity. The addition of antimicrobial silver nanoparticles will provide a secondary, chemical mechanism to escalate the microbial response in tandem with the physical puncture of the cells. EXPERIMENTS: Hydrothermal etching is used as a facile method to impart variant nanostrucutres on the titanium substrate to increase the antimicrobial response. Increasing concentrations (0.25 M, 0.50 M, 1.0 M, 2.0 M) of sodium hydroxide etching solution were used to provide differing degrees of nanostructured morphology on the surface after 3 h of heating at 150 °C. This produced titanium nanospikes, nanoblades, and nanowires, respectively, as a function of etchant concentration. These substrates then provided an interface for the deposition of silver nanoparticles via a reduction pathway. Methicillin-resistant Staphylococcous aureus (MRSA) and Candida auris (C. auris) were used as model bacteria and fungi, respectively, to test the effectiveness of the nanostructured titanium with and without silver nanoparticles, and the bio-interactions at the interface. FINDINGS: The presence of nanostructure increased the bactericidal response of titanium against MRSA from â¼ 10 % on commercially pure titanium to a maximum of â¼ 60 % and increased the fungicidal response from â¼ 10 % to â¼ 70 % in C. auris. Introducing silver nanoparticles increased the microbiocidal response to â¼ 99 % towards both bacteria and fungi. Importantly, this study highlights that nanostructure alone is not sufficient to develop a highly antimicrobial titanium substrate. A dual-action, physical and chemical antimicrobial approach is better suited to produce highly effective antibacterial and antifungal surface technologies.
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Anti-Infecciosos , Nanopartículas Metálicas , Nanoestruturas , Prata/farmacologia , Prata/química , Titânio/farmacologia , Titânio/química , Nanopartículas Metálicas/química , Antifúngicos/farmacologia , Hidróxido de Sódio , Nanoestruturas/química , Bactérias , Antibacterianos/farmacologia , Antibacterianos/química , Ligas/farmacologia , Anti-Infecciosos/farmacologia , Materiais Biocompatíveis/farmacologiaRESUMO
Cryptococcus neoformans is a yeast-like fungus that can cause the life-threatening disease cryptococcal meningitis. Numerous reports have shown increased resistance of this fungus against antifungal treatments, such as fluconazole (Fluc), contributing to an 80% global mortality rate. This work presents a novel approach to improve the delivery of the antifungal agent Fluc and increase the drug's targetability and availability at the infection site. Exploiting the acidic environment surrounding a C. neoformans infected site, we have developed pH-sensitive lipid nanoparticles (LNP) encapsulating Fluc to inhibit the growth of resistant C. neoformans. The LNP-Fluc delivery system consists of a neutral lipid monoolein (MO) and a novel synthetic ionizable lipid 2-morpholinoethyl oleate (O2ME). At neutral pH, because of the presence of O2ME, the nanoparticles are neutral and exhibit a liquid crystalline hexagonal nanostructure (hexosomes). At an acidic pH, they are positively charged with a cubic nanostructure (cubosomes), which facilitates the interaction with the negatively charged fungal cell wall. This interaction results in the MIC50 and MIC90 values of the LNP-Fluc being significantly lower than that of the free-Fluc control. Confocal laser scanning microscopy and scanning electron microscopy further support the MIC values, showing fungal cells exposed to LNP-Fluc at acidic pH were heavily distorted, demonstrating efflux of cytoplasmic molecules. In contrast, fungal cells exposed to Fluc alone showed cell walls mostly intact. This current study represents a significant advancement in delivering targeted antifungal therapy to combat fungal antimicrobial resistance.
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Hydroxyapatite (HAp)-coated metallic implants are known for their excellent bioactivity and osteoconductivity. However, infections associated with the microstructure of the HAp coatings may lead to implant failures as well as increased morbidity and mortality. This work addresses the concerns about infections by developing novel composite coatings of HAp and gallium liquid metal (GaLM) using atmospheric plasma spray (APS) as the coating technique. Five weight percent Ga was mixed into a commercially supplied HAp powder using an orbital shaker; then, the HAp-Ga particle feedstock was coated onto Ti6Al4V substrates using the APS technique. The X-ray diffraction results indicated that Ga did not form any Ga-related phases in either the HAp-Ga powder or the respective coating. The GaLM filled the pores of the HAp coating presented both on the top surface and within the coating, especially at voids and cracks, to prevent failures of the coating at these locations. The wettability of the surface was changed from hydrophobic for the HAp coating to hydrophilic for the HAp-Ga composite coating. Finally, the HAp-Ga coating presented excellent antibacterial efficacies against both initial attachments and established biofilms generated from methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa after 18 h and 7 days of incubation in comparison to the control HAp coating. This study shows that GaLM improves the antibacterial properties of HAp-based coatings without sacrificing the beneficial properties of conventional HAp coatings. Thus, the HAp-Ga APS coating is a viable candidate for antibacterial coatings.