3D-printed biosurfactant-chitosan antibacterial coating for the prevention of silicone-based associated infections.

Infections associated with the surfaces of medical devices represent a critical problem due to biofilm formation and the growing resistance towards antibacterial drugs. This is particularly relevant in commonly used invasive devices such as silicone-based ones where a demand for alternative antibiofilm surfaces is increasing. In this work, an antimicrobial chitosan-biosurfactant hydrogel mesh was produced by 3D-printing. The 3D structure was designed to coat polydimethylsiloxane-based medical devices for infection prevention. Additionally, the porous 3D structure allows the incorporation of customized bioactive components. For this purpose, two biosurfactants (surfactin and sophorolipids) were biosynthesized and tested for their antimicrobial activity. In addition, the printing of surfactant-chitosan-based coatings was optimized, and the resulting 3D structures were characterized (i.e., wettability, FTIR-ATR, antimicrobial activity, and biocompatibility). Compared with surfactin, the results showed a better yield and higher antibacterial activity against Gram-positive bacteria for sophorolipids (SLs). Thus, SLs were used to produce chitosan-based 3D-printed coatings. Overall, the SLs-impregnated coatings showed the best antibacterial activity against Staphylococcus aureus planktonic bacteria (61 % of growth inhibition) and antibiofilm activity (2 log units reduction) when compared to control. Furthermore, concerning biocompatibility, the coatings were cytocompatible towards human dermal fibroblasts. Finally, the coating presented a mesh suitable to be filled with a model bioactive compound (i.e., hyaluronic acid), paving the way to be used for customized therapeutics.

Improving Chitosan Hydrogels Printability: A Comprehensive Study on Printing Scaffolds for Customized Drug Delivery.

Chitosan is an interesting polymer to produce hydrogels suitable for the 3D printing of customized drug delivery systems. This study aimed at the achievement of chitosan-based scaffolds suitable for the incorporation of active components in the matrix or loaded into the pores. Several scaffolds were printed using different chitosan-based hydrogels. To understand which parameters would have a greater impact on printability, an optimization study was conducted. The scaffolds with the highest printability were obtained with a chitosan hydrogel at 2.5 wt%, a flow speed of 0.15 mm/s and a layer height of 0.41 mm. To improve the chitosan hydrogel printability, starch was added, and a design of experiments with three factors and two responses was carried out to find out the optimal starch supplementation. It was possible to conclude that the addition of starch (13 wt%) to the chitosan hydrogel improved the structural characteristics of the chitosan-based scaffolds. These scaffolds showed potential to be tested in the future as drug-delivery systems.

Using plasma-mediated covalent functionalization of rhamnolipids on polydimethylsiloxane towards the antimicrobial improvement of catheter surfaces.

Controlling bacterial biofilm formation on silicone-based bloodstream catheters is of great concern to prevent related-infections. In this study, rhamnolipids (RLs), glycolipid biosurfactants, specifically a RLs mixture and the purified di-RL (RhaRhaC10:0C10:0) were covalently bonded to silicone with the intention of reaching long-lasting antibiofilm surfaces. RLs mixture and di-RL were identified by an UHPLC-MS method that also allowed the confirmation of compound isolation by automated flash chromatography. Silicone surfaces underwent air-plasma treatment, inducing reactive oxygen radicals able to promote the RLs grafting that was confirmed by contact angle, FTIR-ATR and AFM measurements. The antibiofilm activity towards different Gram positive strains was evaluated by colony forming units (CFU) count and confocal laser microscopy. In addition, protein adsorption and biocompatibility were also investigated. RLs were successfully grafted onto silicone and RLs mixture and RhaRhaC10C10:0 functionalized specimens reduced the biofilm formation over 2.3 log units against methicillin sensitive Staphylococcus aureus. Additionally, a decrease of 1 log unit was observed against methicillin resistant S. aureus and S. epidermidis. Functionalized samples showed cytocompatibility towards human dermal fibroblasts, hemocompatibility and no vascular irritation potential. The results mentioned above revealed a synergy between the antimicrobial and the anti-adhesive properties of RLs, making these compounds good candidates for the improvement of the medical devices antibiofilm properties.

A Glance at Antimicrobial Strategies to Prevent Catheter-Associated Medical Infections.

Urinary and intravascular catheters are two of the most used invasive medical devices; however, microbial colonization of catheter surfaces is responsible for most healthcare-associated infections (HAIs). Several antimicrobial-coated catheters are available, but recurrent antibiotic therapy can decrease their potential activity against resistant bacterial strains. The aim of this Review is to question the actual effectiveness of currently used (coated) catheters and describe the progress and promise of alternative antimicrobial coatings. Different strategies have been reviewed with the common goal of preventing biofilm formation on catheters, including release-based approaches using antibiotics, antiseptics, nitric oxide, 5-fluorouracil, and silver as well as contact-killing approaches employing quaternary ammonium compounds, chitosan, antimicrobial peptides, and enzymes. All of these strategies have given proof of antimicrobial efficacy by modifying the physiology of pathogens or disrupting their structural integrity. The aim for synergistic approaches using multitarget processes and the combination of both antifouling and bactericidal properties holds potential for the near future. Despite intensive research in biofilm preventive strategies, laboratorial studies still present some limitations since experimental conditions usually are not the same and also differ from biological conditions encountered when the catheter is inserted in the human body. Consequently, in most cases, the efficacy data obtained from in vitro studies is not properly reflected in the clinical setting. Thus, further well-designed clinical trials and additional cytotoxicity studies are needed to prove the efficacy and safety of the developed antimicrobial strategies in the prevention of biofilm formation at catheter surfaces.

A scope at antifouling strategies to prevent catheter-associated infections.

The use of invasive medical devices is becoming more common nowadays, with catheters representing one of the most used medical devices. However, there is a risk of infection associated with the use of these devices, since they are made of materials that are prone to bacterial adhesion with biofilm formation, often requiring catheter removal as the only therapeutic option. Catheter-related urinary tract infections (CAUTIs) and central line-associated bloodstream infections (CLABSIs) are among the most common causes of healthcare-associated infections (HAIs) worldwide while endotracheal intubation is responsible for ventilator-associated pneumonia (VAP). Therefore, to avoid the use of biocides due to the potential risk of bacterial resistance development, antifouling strategies aiming at the prevention of bacterial adherence and colonization of catheter surfaces represent important alternative measures. This review is focused on the main strategies that are able to modify the physical or chemical properties of biomaterials, leading to the creation of antiadhesive surfaces. The most promising approaches include coating the surfaces with hydrophilic polymers, such as poly(ethylene glycol) (PEG), poly(acrylamide) and poly(acrylates), betaine-based zwitterionic polymers and amphiphilic polymers or the use of bulk-modified poly(urethanes). Natural polysaccharides and its modifications with heparin, have also been used to improve hemocompatibility. Recently developed bioinspired techniques yielding very promising results in the prevention of bacterial adhesion and colonization of surfaces include slippery liquid-infused porous surfaces (SLIPS) based on the superhydrophilic rim of the pitcher plant and the Sharklet topography inspired by the shark skin, which are potential candidates as surface-modifying approaches for biomedical devices. Concerning the potential application of most of these strategies in catheters, more in vivo studies and clinical trials are needed to assure their efficacy and safety for possible future use.

Mind the Microgap in Iridescent Cellulose Nanocrystal Films.

A new photonic structure is produced from cellulose nanocrystal iridescent films reflecting both right and left circularly polarized light. Micrometer-scale planar gaps perpendicular to the films' cross-section between two different left-handed films' cholesteric domains are impregnated with a nematic liquid crystal. This photonic feature is reversibly tuned by the application of an electric field or a temperature variation.

Novel Antibacterial Agents: An Emergent Need to Win the Battle Against Infections.

BACKGROUND: Multiple strategies have been recommended for prevention and control of antibacterial resistance. Solutions will need to be found soon if we are not to run the serious risk of losing the ability to treat bacterial infections, especially the ones arising from multi-resistant strains. Deep knowledge of the resistance mechanisms followed by novel therapeutic drugs and vaccines are needed. A consolidated, multidisciplinary and regulated strategy is required by this challenge. OBJECTIVE: This review will be focused on new strategies to control infections. Among strategies to tackle antibiotic resistance that have been under investigation, are the use of antimicrobial peptides, phage therapy and phage enzymes, therapeutic antibodies, quorum sensing inhibitors and, finally, the antibacterial nanomedicines. Although all of the approaches seem to be effective, and at least one of them has been in use for relatively a long time (phage therapy), antibacterial nanomedicines show the most diverse range of different approaches regarding potential translation to clinics. RESULTS & CONCLUSION: Several advances have been made but a great effort is still mandatory in order to reach feasible, effective and marketable novel antimicrobial products.