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      Recent Advances in Surface Nanoengineering for Biofilm Prevention and Control. Part II: Active, Combined Active and Passive, and Smart Bacteria-Responsive Antibiofilm Nanocoatings

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          Abstract

          The second part of our review describing new achievements in the field of biofilm prevention and control, begins with a discussion of the active antibiofilm nanocoatings. We present the antibiofilm strategies based on antimicrobial agents that kill pathogens, inhibit their growth, or disrupt the molecular mechanisms of biofilm-associated increase in resistance and tolerance. These agents of various chemical structures act through a plethora of mechanisms targeting vital bacterial metabolic pathways or cellular structures like cell walls and cell membranes or interfering with the processes that underlie different stages of the biofilm life cycle. We illustrate the latter action mechanisms through inhibitors of the quorum sensing signaling pathway, inhibitors of cyclic-di-GMP signaling system, inhibitors of (p)ppGpp regulated stringent response, and disruptors of the biofilm extracellular polymeric substances matrix (EPS). Both main types of active antibiofilm surfaces, namely non-leaching or contact killing systems, which rely on the covalent immobilization of the antimicrobial agent on the surface of the coatings and drug-releasing systems in which the antimicrobial agent is physically entrapped in the bulk of the coatings, are presented, highlighting the advantages of each coating type in terms of antibacterial efficacy, biocompatibility, selective toxicity, as well as drawbacks and limitations. Developments regarding combined strategies that join in a unique platform, both passive and active elements are not omitted. In such platforms with dual functionality, passive and active strategies can be applied either simultaneously or sequentially. We especially emphasize those systems that can be reversely and repeatedly switched between the non-fouling status and the bacterial killing status, thereby allowing several bacteria-killing/surface regeneration cycles to be performed without significant loss of the initial bactericidal activity. Eventually, smart antibiofilm coatings that release their antimicrobial payload on demand, being activated by various triggers such as changes in local pH, temperature, or enzymatic triggers, are presented. Special emphasis is given to the most recent trend in the field of anti-infective surfaces, specifically smart self-defensive surfaces for which activation and switch to the bactericidal status are triggered by the pathogens themselves.

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          Most cited references129

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          Negligible particle-specific antibacterial activity of silver nanoparticles.

          For nearly a decade, researchers have debated the mechanisms by which AgNPs exert toxicity to bacteria and other organisms. The most elusive question has been whether the AgNPs exert direct "particle-specific" effects beyond the known antimicrobial activity of released silver ions (Ag(+)). Here, we infer that Ag(+) is the definitive molecular toxicant. We rule out direct particle-specific biological effects by showing the lack of toxicity of AgNPs when synthesized and tested under strictly anaerobic conditions that preclude Ag(0) oxidation and Ag(+) release. Furthermore, we demonstrate that the toxicity of various AgNPs (PEG- or PVP- coated, of three different sizes each) accurately follows the dose-response pattern of E. coli exposed to Ag(+) (added as AgNO(3)). Surprisingly, E. coli survival was stimulated by relatively low (sublethal) concentration of all tested AgNPs and AgNO(3) (at 3-8 μg/L Ag(+), or 12-31% of the minimum lethal concentration (MLC)), suggesting a hormetic response that would be counterproductive to antimicrobial applications. Overall, this work suggests that AgNP morphological properties known to affect antimicrobial activity are indirect effectors that primarily influence Ag(+) release. Accordingly, antibacterial activity could be controlled (and environmental impacts could be mitigated) by modulating Ag(+) release, possibly through manipulation of oxygen availability, particle size, shape, and/or type of coating.
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            Mechanisms of nanotoxicity: Generation of reactive oxygen species⋆

            Nanotechnology is a rapidly developing field in the 21 st century, and the commercial use of nanomaterials for novel applications is increasing exponentially. To date, the scientific basis for the cytotoxicity and genotoxicity of most manufactured nanomaterials are not understood. The mechanisms underlying the toxicity of nanomaterials have recently been studied intensively. An important mechanism of nanotoxicity is the generation of reactive oxygen species (ROS). Overproduction of ROS can induce oxidative stress, resulting in cells failing to maintain normal physiological redox-regulated functions. This in turn leads to DNA damage, unregulated cell signaling, change in cell motility, cytotoxicity, apoptosis, and cancer initiation. There are critical determinants that can affect the generation of ROS. These critical determinants, discussed briefly here, include: size, shape, particle surface, surface positive charges, surface-containing groups, particle dissolution, metal ion release from nanometals and nanometal oxides, UV light activation, aggregation, mode of interaction with cells, inflammation, and pH of the medium.
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              Facile Conjugation of Biomolecules onto Surfaces via Mussel Adhesive Protein Inspired Coatings.

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                Author and article information

                Journal
                Nanomaterials (Basel)
                Nanomaterials (Basel)
                nanomaterials
                Nanomaterials
                MDPI
                2079-4991
                04 August 2020
                August 2020
                : 10
                : 8
                : 1527
                Affiliations
                [1 ]“Costin Nenitzescu” Department of Organic Chemistry, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, G. Polizu Street 1–7, 011061 Bucharest, Romania; paul.balaure@ 123456upb.ro
                [2 ]Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, G. Polizu Street 1–7, 011061 Bucharest, Romania
                Author notes
                [* ]Correspondence: agrumezescu@ 123456upb.ro ; Tel.: +40-21-402-39-97
                [†]

                These authors contributed equally to this work.

                Article
                nanomaterials-10-01527
                10.3390/nano10081527
                7466637
                32759748
                5e77dd5e-fb6d-45c6-9872-994189d7f8af
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 June 2020
                : 28 July 2020
                Categories
                Review

                biofilm-related pathogenic infections,contact-killing nanocoatings,drug-eluting nanocoatings,bacteria-triggered antimicrobial-releasing systems,inhibitors of bacterial signaling processes,dispersion of the biofilm matrix,combined active and passive strategies,antibiofilm platforms with reversibly switchable functionality between the non-fouling status and the bactericidal status,smart antibiofilm coatings,self-defensive coatings

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