Metals and alloys, including stainless steel, titanium and its alloys, cobalt alloys, and other metals and alloys have been widely used clinically as implant materials, but implant-related infection or inflammation is still one of the main causes of implantation failure. The bacterial infection or inflammation that seriously threatens human health has already become a worldwide complaint. Antibacterial metals and alloys recently have attracted wide attention for their long-term stable antibacterial ability, good mechanical properties and good biocompatibility and. In this review, common antibacterial alloying elements, antibacterial standards and testing methods were introduced. Recent developments in the design and manufacturing of antibacterial metal alloys containing various antibacterial agents were described in detail, including antibacterial stainless steel, antibacterial titanium alloy, antibacterial zinc and alloy, antibacterial magnesium and alloy, antibacterial cobalt alloy, and other antibacterial metals and alloys. Researches on the antibacterial properties, mechanical properties, corrosion resistance and biocompatibility of antibacterial metals and alloys have been summarized in detail for the first time. It is hoped that this review could help researchers understand the development of antibacterial alloys in a timely manner, thereby could promote the development of antibacterial metal alloys and the clinical application.© 2021 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

Direct observations have clearly shown that biofilm bacteria predominate, numerically and metabolically, in virtually all nutrient-sufficient ecosystems. Therefore, these sessile organisms predominate in most of the environmental, industrial, and medical problems and processes of interest to microbiologists. If biofilm bacteria were simply planktonic cells that had adhered to a surface, this revelation would be unimportant, but they are demonstrably and profoundly different. We first noted that biofilm cells are at least 500 times more resistant to antibacterial agents. Now we have discovered that adhesion triggers the expression of a sigma factor that derepresses a large number of genes so that biofilm cells are clearly phenotypically distinct from their planktonic counterparts. Each biofilm bacterium lives in a customized microniche in a complex microbial community that has primitive homeostasis, a primitive circulatory system, and metabolic cooperativity, and each of these sessile cells reacts to its special environment so that it differs fundamentally from a planktonic cell of the same species.

The biofilm matrix is a dynamic environment in which the component microbial cells appear to reach homeostasis and are optimally organized to make use of all available nutrients. The major matrix components are microbial cells, polysaccharides and water, together with excreted cellular products. The matrix therefore shows great microheterogeneity, within which numerous microenvironments can exist. Although exopolysaccharides provide the matrix framework, a wide range of enzyme activities can be found within the biofilm, some of which will greatly affect structural integrity and stability.

Biofilms--matrix-enclosed microbial accretions that adhere to biological or non-biological surfaces--represent a significant and incompletely understood mode of growth for bacteria. Biofilm formation appears early in the fossil record (approximately 3.25 billion years ago) and is common throughout a diverse range of organisms in both the Archaea and Bacteria lineages, including the 'living fossils' in the most deeply dividing branches of the phylogenetic tree. It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments. Recent advances show that biofilms are structurally complex, dynamic systems with attributes of both primordial multicellular organisms and multifaceted ecosystems. Biofilm formation represents a protected mode of growth that allows cells to survive in hostile environments and also disperse to colonize new niches. The implications of these survival and propagative mechanisms in the context of both the natural environment and infectious diseases are discussed in this review.

This review covers the most recent developments of inorganic and organic-inorganic composite coatings for orthopedic implants, providing the interface with living tissue and with potential for drug delivery to combat infections. Conventional systemic delivery of drugs is an inefficient procedure that may cause toxicity and may require a patient's hospitalization for monitoring. Local delivery of antibiotics and other bioactive molecules maximizes their effect where they are required, reduces potential systemic toxicity and increases timeliness and cost efficiency. In addition, local delivery has broad applications in combating infection-related diseases. Polymeric coatings may present some disadvantages. These disadvantages include limited chemical stability, local inflammatory reactions, uncontrolled drug-release kinetics, late thrombosis and restenosis. As a result, embedding of bioactive compounds and biomolecules within inorganic coatings (bioceramics, bioactive glasses) is attracting significant attention. Recently nanoceramics have attracted interest because surface nanostructuring allows for improved cellular adhesion, enhances osteoblast proliferation and differentiation, and increases biomineralization. Organic-inorganic composite coatings, which combine biopolymers and bioactive ceramics that mimick bone structure to induce biomineralization, with the addition of biomolecules, represent alternative systems and ideal materials for "smart" implants. In this review, emphasis is placed on materials and processing techniques developed to advance the therapeutic use of biomolecules-eluting coatings, based on nanostructured ceramics. One part of this report is dedicated to inorganic and composite coatings with antibacterial functionality.Inorganic and composite nanotechnology-based coating methods have recently been developed for orthopedic applications, with the main goal to provide bactericide and other enhanced properties, which may result in reduced need for pharmaceutical interventions and overall more cost effective orthopedic procedures. This review discusses key aspects of the above developments.Copyright © 2011 Elsevier Inc. All rights reserved.

In this paper, the possible interactions between 5-fluorouracil (5FU) as an anticancer drug and gallium nitride (GaN) nanocage (NC) in aqueous solution have been investigated using DFT/CPCM/B3LYP-D/6-31G(d,p) level of theory. Eleven different orientations were used to mimic the 5FU adsorbed on GaN (5FU@GaNNC). To investigate the interaction mechanism between the two components, the adsorption energies and thermodynamic parameters, the electronic properties such as the energies and orbitals distribution of the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), the HOMO-LUMO energy gaps (E), the density of states (DOS), partial DOS (PDOS), and the molecular electrostatic potential (MEP) have been calculated and compared. The natural bond orbitals (NBOs) and the quantum theory of atoms in molecules (QTAIM) calculations have been applied for understanding chemical interactions and chemical bonding. Additionally, some quantum molecular descriptors were calculated for the understanding of molecular reactivity. Main results revealed that (1) the key factor that leads to stabilization of the formed complex/s is the relocation of one of the H atoms that originally belonging to one of the N atoms in 5FU to one of the nearest Ga atoms in GaNNC and (2) the adsorption energies for the eleven adsorbed systems are relatively larger compared with reported similar systems indicating from a theoretical point of view, a probable chemisorption type of adsorption and the privilege of GaNNC as a carrier for 5FU drug. Graphical abstract Simulation of the most stable adsorbed system of 5-fluorouracil anticancer drug on Gallium nitride nanocage.

Chemotherapeutic metal-based compounds are effective anticancer agents; however, their cytotoxic profile and significant side effects limit their wide application. Natural products, especially flavonoids, are a prominent alternative source of anticancer agents that can be used as ligands for the generation of new bioactive complexes with metal ions of known biochemical and pharmacological activities. Herein, we present the synthesis and detailed structural and physicochemical characterizations of three novel complex assemblies of Ga(iii) with the flavonoid chrysin and the ancillary aromatic chelators 1,10-phenanthroline, 2,2'-bipyridine and imidazole. The complexes constitute the only crystallographically characterized structures having a metal core from the boron group elements and a flavonoid as the ligand. The in vitro biological evaluation of the three complexes in a series of cancer cell lines of different origin established their cytotoxicity and ROS generating potential. In particular, the Ga(iii)-chrysin-imidazole complex displayed the highest anticancer efficacy against all cancer cell lines with IC50 values in the low micromolar range (<1.18 μM), a result worth further investigation.

Gallium has a long history as a diagnostic and chemotherapeutic agent. The pharmacological properties of Ga(III) rely on chemical mimicry; when Ga(III) is exogenously supplied to living cells it can replace Fe(III) within target molecules, thereby perturbing bacterial metabolism. Ga(III)-induced metabolic distresses are dramatic in fast-growing cells, like bacterial cells. Interest in the antibacterial properties of Ga(III) has been raised by the compelling need for novel drugs to combat multidrug-resistant bacteria and by the shortage of new antibiotic candidates in the pharmaceutical pipeline. Ga(III) activity has been demonstrated, both in vitro and in animal models of infections, on several bacterial pathogens, also including intracellular and biofilm-forming bacteria. Ga(III) activity is affected by iron availability and the metabolic state of the cell, being maximal in iron-poor media and in respiring cells. Synergism between Ga(III) and antibiotics holds promise as last resort therapy for infections sustained by pandrug-resistant bacteria.

Gallium (Ga) is a semi-metallic element that displays antitumor, antiresorptive, anti-inflammatory and immunosuppressive properties. Among all these properties, antitumor properties were the most extensively applied and have shown efficacy in treatment of Paget's disease, myeloma and hypercalcemia in cases of malignancy. By contrast, no clinical trials have been conducted in prevention and/or treatment of osteoporosis. In this article I focus on Ga effects on bone tissue and cells, as well as on molecular mechanisms governing Ga internalization into cells. Eventually, the potential of Ga as an antiosteoporotic agent is discussed.Copyright © 2012 Elsevier Ltd. All rights reserved.

Mycobacterium tuberculosis and M. avium complex (MAC) enter and multiply within monocytes and macrophages in phagosomes. In vitro growth studies using standard culture media indicate that siderophore-mediated iron (Fe) acquisition plays a critical role in the growth and metabolism of both M. tuberculosis and MAC. However, the applicability of such studies to conditions within the macrophage phagosome is unclear, due in part to the absence of experimental means to inhibit such a process. Based on the ability of gallium (Ga(3+)) to concentrate within mononuclear phagocytes and on evidence that Ga disrupts cellular Fe-dependent metabolic pathways by substituting for Fe(3+) and failing to undergo redox cycling, we hypothesized that Ga could disrupt Fe acquisition and Fe-dependent metabolic pathways of mycobacteria. We find that Ga(NO(3))(3) and Ga-transferrin produce an Fe-reversible concentration-dependent growth inhibition of M. tuberculosis strains and MAC grown extracellularly and within human macrophages. Ga is bactericidal for M. tuberculosis growing extracellularly and within macrophages. Finally, we provide evidence that exogenously added Fe is acquired by intraphagosomal M. tuberculosis and that Ga inhibits this Fe acquisition. Thus, Ga(NO(3))(3) disruption of mycobacterial Fe metabolism may serve as an experimental means to study the mechanism of Fe acquisition by intracellular mycobacteria and the role of Fe in intracellular survival. Furthermore, given the inability of biological systems to discriminate between Ga and Fe, this approach could have broad applicability to the study of Fe metabolism of other intracellular pathogens.

Rhodococcus equi, a facultative intracellular bacterium, causes severe pneumonia in foals. Evidence suggests that most foals become infected very early in life, when they have immature or ineffective innate immune responses. This study evaluated the antimicrobial activity of gallium against R. equi, as a potential chemoprophylactic and therapeutic agent. Rhodococcus equi was grown in media with various concentrations of gallium nitrate (GN), with and without excess iron. GN significantly inhibited growth and killed R. equi, and these effects were abolished with excess iron. Antimicrobial effects of Ga appear to be related to its interference with iron metabolism. Mice were treated orally with gallium maltolate (GaM), 10 or 50 mg/kg BW, or distilled H2O prior to and after experimental infection with R. equi. Six days post-infection, organs were harvested and R. equi concentrations assessed, and serum gallium concentrations determined. GaM was absorbed in a dose-dependent manner, and R. equi tissue burdens were greater in control mice than in all GaM-treated mice. GaM may aid in the control of disease by preventing development of overwhelming R. equi tissue burdens prior to the establishment of requisite innate and adaptive immune responses.

Ga(3+) is a semimetal element that competes for the iron-binding sites of transporters and enzymes. We investigated the activity of gallium maltolate (GaM), an organic gallium salt with high solubility, against laboratory and clinical strains of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), and methicillin-resistant S. epidermidis (MRSE) in logarithmic or stationary phase and in biofilms. The MICs of GaM were higher for S. aureus (375 to 2000 microg/ml) than S. epidermidis (94 to 200 microg/ml). Minimal biofilm inhibitory concentrations were 3,000 to >or=6,000 microg/ml (S. aureus) and 94 to 3,000 microg/ml (S. epidermidis). In time-kill studies, GaM exhibited a slow and dose-dependent killing, with maximal action at 24 h against S. aureus of 1.9 log(10) CFU/ml (MSSA) and 3.3 log(10) CFU/ml (MRSA) at 3x MIC and 2.9 log(10) CFU/ml (MSSE) and 4.0 log(10) CFU/ml (MRSE) against S. epidermidis at 10x MIC. In calorimetric studies, growth-related heat production was inhibited by GaM at subinhibitory concentrations; and the minimal heat inhibition concentrations were 188 to 4,500 microg/ml (MSSA), 94 to 1,500 microg/ml (MRSA), and 94 to 375 microg/ml (MSSE and MRSE), which correlated well with the MICs. Thus, calorimetry was a fast, accurate, and simple method useful for investigation of antimicrobial activity at subinhibitory concentrations. In conclusion, GaM exhibited activity against staphylococci in different growth phases, including in stationary phase and biofilms, but high concentrations were required. These data support the potential topical use of GaM, including its use for the treatment of wound infections, MRSA decolonization, and coating of implants.

Gallium, a group IIIa metal, shares chemical properties with iron. Studies have shown that gallium-based compounds have potential therapeutic activity against certain cancers and infectious microorganisms. By functioning as an iron mimetic, gallium perturbs iron-dependent proliferation processes in tumor cells. Gallium's action on iron homeostasis leads to disruption of ribonucleotide reductase, mitochondrial function, and the regulation of transferrin receptor and ferritin. In addition, gallium nitrate stimulates an increase in mitochondrial reactive oxygen species in cells which triggers downstream upregulation of metallothionein and hemoxygenase-1. Gallium's anti-infective activity against bacteria and fungi results from disruption of microbial iron utilization through mechanisms which include gallium binding to siderophores and downregulation of bacterial iron uptake. Gallium compounds lack cross-resistance to conventional chemotherapeutic drugs and antibiotics thus making them attractive agents for drug development. This review will focus on the mechanisms of action of gallium with emphasis on its interaction with iron and iron proteins.Copyright © 2016 Elsevier B.V. All rights reserved.

To test the cytotoxicity of Gallium alloy, a new mercury-free dental restorative material.L-929 mouse fibroblasts were used to detect the cell relative proliferation rate of Gallium alloy and high-copper amalgam by MTT-assay.The results indecated that the relative growth rate induced by Gallium alloy was high (93.0% +/- 4.9% 2ds, 102.0% +/- 3.5% 4ds, 107.2% +/- 4.2% 7ds), and the cytotoxicity of Gallium alloy was 0 grade according to the Test Standard of Shanghai Medical Biomaterial, meaning Gallium alloy had no significant cytotoxicity and the relative growth rate of Gallium alloy was higher than that of high-copper amalgam. The high-copper amalgam showed medium cytotoxicity.Gallium alloy has no significant cytotoxicity.

Magnetostrictive alloys have attracted increasing attention in biomedical applications because of the ability to generate reversible deformation in the presence of external magnetic fields. This review focuses on the advances in magnetostrictive alloys and their biomedical applications. The theories of magnetostriction are systematically summarized. The different types of magnetostrictive alloys and their preparation methods are also reviewed in detail. The magnetostrictive strains and phase compositions of typical magnetostrictive alloys, including iron based, rare-earth based and ferrite materials, are presented. Besides, a variety of approaches to preparing rods, blocks and films of magnetostriction materials, as well as the corresponding methods and setups for magnetostriction measurement, are summarized and discussed. Moreover, the interactions between magnetostrictive alloys and cells are analyzed and emphasis is placed on the transduction and transformation process of mechanochemical signals induced by magnetostriction. The latest applications of magnetostrictive alloys in remote microactuators, magnetic field sensors, wireless implantable devices and biodegradable implants are also reviewed. Furthermore, future research directions of magnetostrictive alloys are prospected with focus on their potential applications in remote cell actuation and bone repair.© 2021 The Authors.

The variation of stacking fault energy (SFE) in a number of binary Cu alloys is predicted through considering the Suzuki segregation by the full potential linearly augmented plane wave (FPLAPW) method. The calculated results show that some solute atoms (Mg, Al, Si, Zn, Ga, Ge, Cd, Sn, and Pb), which prefer to form the Suzuki segregation, may decrease the value of SFE; while the others (Ti, Mn, Fe, Ni, Zr, Ag, and Au), which do not cause the Suzuki segregation may not decrease the SFE. Furthermore, it is interesting to find that the former alloying elements are located on the right of Cu group while the latter on the left of Cu group in the periodic table of elements. The intrinsic reasons for the new findings can be traced down to the valences electronic structure of solute and Cu atoms, i.e., the similarity of valence electronic structure between solute and Cu atoms increases the value of SFE, while the difference decreases the value of SFE.

The role metals play in living organisms is well established and subject to extensive research. Some of them participate in electron-exchange reactions. Such reactions cause generation of free radicals that can adversely impact biological systems, as a result of oxidative stress. The impact of 'non-biological' metals on oxidative stress is also a worthy pursuit due to the crucial role they play in modern civilization. Lanthanides (Ln) are widely used in modern technology. As a result, human exposure to them is increasing. They have a number of established medical applications and are being extensively researched for their potential antiviral, anticancer and anti-inflammatory properties. The present review focuses on lanthanum (La) and its impact on oxidative stress. Another metal, widely used in modern high-tech is gallium (Ga). In some respects, it shows certain similarities to La, therefore it is a subject of the present review as well. Both metals exhibit ionic mimicry which allows them to specifically target malignant cells, initiating apoptosis that makes their simple salts and coordination complexes promising candidates for future anticancer agents.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Titanium embedded with silver nanoparticles (Ag NPs) using a single step silver plasma immersion ion implantation (Ag-PIII) demonstrate micro-galvanic effects that give rise to both controlled antibacterial activity and excellent compatibility with osteoblasts. Scanning electron microscopy (SEM) shows that nanoparticles with average sizes of about 5 nm and 8 nm are formed homogeneously on the titanium surface after undergoing Ag-PIII for 0.5 h and 1 h, respectively. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) indicate that those nanoparticles are metallic silver produced on and underneath the titanium surface via a local nucleation process from the solid solution of α-Ti(Ag). The Ag-PIII samples inhibit the growth of both Staphylococcus aureus and Escherichia coli while enhancing proliferation of the osteoblast-like cell line MG63. Electrochemical polarization and Zeta potential measurements demonstrate that the low surface toxicity and good cytocompatibility are related to the micro-galvanic effect between the Ag NPs and titanium matrix. Our results show that the physico-chemical properties of the Ag NPs are important in the control of the cytotoxicity and this study opens a new window for the design of nanostructured surfaces on which the biological actions of the Ag NPs can be accurately tailored.Copyright © 2010 Elsevier Ltd. All rights reserved.

Although titanium embedded with silver nanoparticles (Ag-NPs@Ti) are suitable for biomedical implants because of the good cytocompatibility and antibacterial characteristics, the exact antibacterial mechanism is not well understood. In the present work, the antibacterial mechanisms of Ag-NPs@Ti prepared by plasma immersion ion implantation (PIII) are explored in details. The antibacterial effects of the Ag-NPs depend on the conductivity of the substrate revealing the importance of electron transfer in the antibacterial process. In addition, electron transfer between the Ag-NPs and titanium substrate produces bursts of reactive oxygen species (ROS) in both the bacteria cells and culture medium. ROS leads to bacteria death by inducing intracellular oxidation, membrane potential variation, and cellular contents release and the antibacterial ability of Ag-NPs@Ti is inhibited appreciably after adding ROS scavengers. Even though ROS signals are detected from osteoblasts cultured on Ag-NPs@Ti, the cell compatibility is not impaired. This electron-transfer-based antibacterial process which produces ROS provides insights into the design of biomaterials with both antibacterial properties and cytocompatibility.Copyright © 2017 Elsevier Ltd. All rights reserved.