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1.
ACS Appl Mater Interfaces ; 16(15): 18449-18458, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38578282

ABSTRACT

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.


Subject(s)
Photochemotherapy , Photosensitizing Agents , Animals , Photosensitizing Agents/chemistry , Anti-Bacterial Agents/chemistry , Biomimetics , Gram-Negative Bacteria , Gram-Positive Bacteria , Bacteria , Postoperative Complications , Mammals
2.
Molecules ; 29(6)2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38542846

ABSTRACT

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.


Subject(s)
Cross Infection , Staphylococcal Infections , Humans , Anti-Bacterial Agents/pharmacology , Staphylococcus aureus , Textiles , Delivery of Health Care
3.
Sci Total Environ ; 916: 170013, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38242452

ABSTRACT

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.


Subject(s)
Nanostructures , Refuse Disposal , Soil Pollutants , Animals , Humans , Soil , Sewage , Ecosystem , Food , Soil Pollutants/analysis , Environment , Food Additives , Water
4.
J Orthop Res ; 42(3): 512-517, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38146070

ABSTRACT

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.


Subject(s)
Biofilms , Consensus
5.
Acta Biomater ; 175: 369-381, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38141932

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents , Staphylococcal Infections , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Staphylococcus aureus/physiology , Vancomycin/pharmacology , Cefazolin/metabolism , Titanium/pharmacology , Staphylococcal Infections/prevention & control , Biofilms , Microbial Sensitivity Tests
6.
ACS Appl Bio Mater ; 7(1): 344-361, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38100088

ABSTRACT

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.


Subject(s)
Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Nanostructures , Cell Adhesion , Titanium/pharmacology , Titanium/chemistry , Bacterial Adhesion , Nanostructures/chemistry , Anti-Infective Agents/pharmacology , Elasticity
7.
Biomimetics (Basel) ; 8(8)2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38132512

ABSTRACT

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.

8.
NPJ Biofilms Microbiomes ; 9(1): 90, 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38030708

ABSTRACT

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.


Subject(s)
Staphylococcal Infections , Vancomycin , Humans , Vancomycin/pharmacology , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Prostheses and Implants
9.
Small ; : e2305469, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37715087

ABSTRACT

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.

10.
ACS Appl Bio Mater ; 6(8): 2925-2943, 2023 08 21.
Article in English | MEDLINE | ID: mdl-37565698

ABSTRACT

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.


Subject(s)
Nanotechnology , Tissue Engineering , Tissue Engineering/methods , Bone and Bones/surgery , Drug Delivery Systems , Wound Healing
11.
ACS Nano ; 17(15): 14406-14423, 2023 08 08.
Article in English | MEDLINE | ID: mdl-37506260

ABSTRACT

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.


Subject(s)
Anti-Infective Agents , Gallium , Metal Nanoparticles , Humans , Gallium/pharmacology , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology
12.
Mar Drugs ; 21(6)2023 Jun 11.
Article in English | MEDLINE | ID: mdl-37367683

ABSTRACT

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.


Subject(s)
Calcium , Nephropidae , Animals , Cattle , Calcium/metabolism , Nephropidae/metabolism , Caseins/metabolism , Biological Availability , Solubility , Minerals , Chitin/metabolism
13.
ACS Appl Mater Interfaces ; 15(26): 31114-31123, 2023 Jul 05.
Article in English | MEDLINE | ID: mdl-37339239

ABSTRACT

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.

14.
iScience ; 26(4): 106493, 2023 Apr 21.
Article in English | MEDLINE | ID: mdl-37091232

ABSTRACT

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.

15.
Polymers (Basel) ; 14(24)2022 Dec 09.
Article in English | MEDLINE | ID: mdl-36559762

ABSTRACT

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.

16.
J Colloid Interface Sci ; 628(Pt B): 1049-1060, 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36049281

ABSTRACT

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 âˆ¼ 10 % on commercially pure titanium to a maximum of âˆ¼ 60 % and increased the fungicidal response from âˆ¼ 10 % to âˆ¼ 70 % in C. auris. Introducing silver nanoparticles increased the microbiocidal response to âˆ¼ 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.


Subject(s)
Anti-Infective Agents , Metal Nanoparticles , Nanostructures , Silver/pharmacology , Silver/chemistry , Titanium/pharmacology , Titanium/chemistry , Metal Nanoparticles/chemistry , Antifungal Agents/pharmacology , Sodium Hydroxide , Nanostructures/chemistry , Bacteria , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Alloys/pharmacology , Anti-Infective Agents/pharmacology , Biocompatible Materials/pharmacology
17.
Article in English | MEDLINE | ID: mdl-35850116

ABSTRACT

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.

18.
ACS Appl Mater Interfaces ; 14(16): 18974-18988, 2022 Apr 27.
Article in English | MEDLINE | ID: mdl-35416647

ABSTRACT

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.


Subject(s)
Gallium , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Durapatite/chemistry , Durapatite/pharmacology , Gallium/pharmacology , Materials Testing , Powders , Surface Properties , Titanium/chemistry
19.
Nat Mater ; 21(3): 359-365, 2022 03.
Article in English | MEDLINE | ID: mdl-35190655

ABSTRACT

Ionogels are compelling materials for technological devices due to their excellent ionic conductivity, thermal and electrochemical stability, and non-volatility. However, most existing ionogels suffer from low strength and toughness. Here, we report a simple one-step method to achieve ultra-tough and stretchable ionogels by randomly copolymerizing two common monomers with distinct solubility of the corresponding polymers in an ionic liquid. Copolymerization of acrylamide and acrylic acid in 1-ethyl-3-methylimidazolium ethyl sulfate results in a macroscopically homogeneous covalent network with in situ phase separation: a polymer-rich phase with hydrogen bonds that dissipate energy and toughen the ionogel; and an elastic solvent-rich phase that enables for large strain. These ionogels have high fracture strength (12.6 MPa), fracture energy (~24 kJ m-2) and Young's modulus (46.5 MPa), while being highly stretchable (~600% strain) and having self-healing and shape-memory properties. This concept can be applied to other monomers and ionic liquids, offering a promising way to tune ionogel microstructure and properties in situ during one-step polymerization.


Subject(s)
Ionic Liquids , Electric Conductivity , Gels/chemistry , Hydrogen Bonding , Ionic Liquids/chemistry , Polymers
20.
Small ; 18(16): e2106342, 2022 04.
Article in English | MEDLINE | ID: mdl-35088534

ABSTRACT

Ultrasmall nanoparticles are often grouped under the broad umbrella term of "nanoparticles" when reported in the literature. However, for biomedical applications, their small sizes give them intimate interactions with biological species and endow them with unique functional physiochemical properties. Carbon quantum dots (CQDs) are an emerging class of ultrasmall nanoparticles which have demonstrated considerable biocompatibility and have been employed as potent theragnostic platforms. These particles find application for increasing drug solubility and targeting, along with facilitating the passage of drugs across impermeable membranes (i.e., blood brain barrier). Further functionality can be triggered by various environmental conditions or external stimuli (i.e., pH, temperature, near Infrared (NIR) light, ultrasound), and their intrinsic fluorescence is valuable for diagnostic applications. The focus of this review is to shed light on the therapeutic potential of CQDs and identify how they travel through the body, reach their site of action, administer therapeutic effect, and are excreted. Investigation into their toxicity and compatibility with larger nanoparticle carriers is also examined. The future of CQDs for theragnostic applications is promising due to their multifunctional attributes and documented biocompatibility. As nanomaterial platforms become more commonplace in clinical treatments, the commercialization of CQD therapeutics is anticipated.


Subject(s)
Nanoparticles , Quantum Dots , Carbon/chemistry , Fluorescence , Nanoparticles/chemistry , Quantum Dots/chemistry
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