Pathogenic Biofilm Prevention and Control through Smart Surface Nanoengineering

Dear Colleagues,

Antimicrobial/antibiotic resistance (AMR/AR) occurs when changes in bacteria and pathogenic organisms mitigate or bypass the effects of the drugs used to treat infections. The rapid global spread of multi- and pan-resistant bacteria, also known as “superbugs”, is of extreme concern and was declared by World Health Organization (WHO) as one of the top ten global threats to public health and food security. The Center for Disease Control and Prevention (CDC) in the USA estimates that, without taking any further action, antibiotic resistance will lead to 10 million deaths globally by 2050 and cost up to USD 100 trillion, posing a formidable challenge to developing new, innovative, high performance tools to combat environmental contamination, microbial fouling of abiotic or biotic surfaces, and body infections with antibiotic-resistant microorganisms. Among the newly emerged arsenal of anti-infective strategies, multifunctional antimicrobial nanocomposites and coatings provide cutting-edge solutions to prevent and control the colonization of indwelling medical devices, scalpels, surgical textiles and wound dressings, and hospital furniture by pathogenic bacteria. Other important application fields are the food and food packaging industries, water system piping, water purification, and wastewater treatment plants.

To make matters worse, bacteria can form biofilms even in body fluid. Biofilms are sessile communities of bacterial cells attached to a surface and embedded in a self-produced sheltering matrix of extracellular polymeric substances (EPS). In the biofilm style of life, bacteria exhibit an altered phenotype with respect to growth rate and gene transcription, which allows bacterial cells to shield themselves from antibiotics as well as to evade the host immune response, thereby rendering our antibiotic arsenal obsolete. It is extremely difficult to get rid of a biofilm once settled, as we need up to a 1000-fold increase in the antibiotic amount to kill bacteria in biofilms than their free-floating counterparts, and biofilms are also very resistant to external forces. 

According to their mode of action, nanostructured antibiofilm surfaces and coatings can be roughly classified as passive anti-biofouling nanocoatings and active contact killing and drug-releasing nanocoatings.

The passive strategy aims either to prevent adhesion of bacteria to surfaces and subsequent biofilm development (the “fouling resistance” approach) or to remove already settled bacteria (the “fouling release” approach). Various nanofabrication processes, which can be divided into the well-known “top-down” and “bottom-up” approaches, enable the synthesis and patterning of biomimetic hierarchical micro- and nanostructured superhydrophobic surfaces with low-adhesion and self-cleaning properties. The most common top-down methods used to pattern surfaces and create three-dimensional (3-D) features on substrates are (i) nanolithography; (ii) dry etching techniques, which can be purely chemical (plasma etching), purely physical (ion beam milling, IBM), or a combination of both (reactive ion etching, RIE); (iii) anodic oxidation; and (iv) laser ablation. In the bottom-up approach, structuring of the surface micro/nanotopographic features is achieved via the sequential controlled deposition of material onto a substrate. We briefly mention here a few of the currently available “bottom-up” methods: sol–gel processing, physical vapor deposition (PVD) with its laser-assisted variants pulsed laser deposition (PLD) and matrix-assisted pulsed laser evaporation (MAPLE), chemical vapor deposition (CVD), self-assembly and bio-assisted synthesis, electrochemical deposition, spraying synthesis, and supercritical fluid synthesis.

The active strategies, rather than repelling or impeding bacteria settlement to a substrate, aim to kill pathogens, inhibit their growth, or disrupt the molecular mechanisms of biofilm-associated increase in resistance and tolerance.

We will end by bringing to your attention some key challenges that must be overcome in order for antimicrobial nanocoatings to become more efficient and truly useful tools in the fight against multi-drug-resistant pathogens. The first issue refers to the control of release kinetics from drug-eluting nanocoatings with the aim to maintain the concentration of the antimicrobial agent within the therapeutic window, that is, at a level large enough to kill bacteria but sufficiently low to limit cytotoxicity towards eukaryotic cells, as long as necessary. An efficient way to control release kinetics is to use polyelectrolyte multilayers (PEMs) formed by layer by layer (LbL) deposition of nanostructured oppositely charged polymeric systems. The second key challenge is aiming to develop of multifunctional coatings with striking features, such as:

A). Smart stimuli-responsive nanocoatings, which have the ability to undergo structural changes in response to a particular endogenous trigger (e.g., small changes in microenvironmental temperature, pH, enzyme activity, or redox potential) or exogenous physical triggers that can be applied externally, such as electrical, ultrasonic, photothermal, magnetic, and mechanical triggers. Due to the structural changes, the subsequent release of the antimicrobial agent occurs. The ultimate form of these controlled release strategies is represented by bacteria-responsive coatings, which deliver their antimicrobial payload only when surrounded or in contact with bacteria, which is extremely advantageous in mitigating unwanted side effects and futile drug delivery.

B). Multi-release coatings, which can co-deliver antibacterial agents with different mechanisms of action, thereby providing a dual advantage, namely reduced induction of bacterial resistance and synergistic antibacterial action. Degradable LbL self-assembled multi-layered coatings have already been used to this end.

C). Multi-approach coatings aim to combine in a single platform both passive and active strategies, thereby circumventing the inherent disadvantages associated with each approach and hopefully providing synergic benefits. Two modes of operating for these unique integrating platforms have emerged: the passive antifouling strategy and the active contact killing, or drug release, strategy can be applied simultaneously or one at a time. In the case of sequential application, both “kill and repel” and “resist and kill” approaches are possible. It is highly desirable to design nanocoatings capable of repeatedly switching between the active contact killing and the passive non-fouling status to preserve their anti-infective properties as long as possible. This only could be achieved if the two forms of the surface can be reversibly transformed into each other.

D). Multi-property coatings are needed, especially for clinical applications, as biomedical devices must fulfill a series of additional requirements such as biocompatibility, lack of toxicity and immunogenicity, mechanical strength, resistance to corrosion and wear, anticoagulation, enhanced bone-integration, and improved overall tissue-integration.

The aim of this Special Issue is to highlight the newest and most significant achievements in developing novel engineered nanostructured antibacterial surface coatings to be applied, especially in the biomedical field, but also in the food industry and water treatment.

We kindly invite you to submit a manuscript(s) for this Special Issue. Full papers, communications, and reviews are all welcome.

Dr. Paul Balaure
Guest Editor

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• superbugs
• nosocomial infections
• passive anti-biofouling nanocoatings
• active contact killing nanocoatings
• active drug-eluting nanocoatings
• smart multifunctional and stimuli-responsive nanocoatings
• combined active and passive strategies applied simultaneously
• combined active and passive strategies applied sequentially
• reversible and repeatedly switching between the non-fouling and bactericidal status