Efficient, simple antibacterial materials to combat implant-associated infections are much in demand. Herein, the development of polyurethanes, both cross-linked thermoset and flexible and versatile thermoplastic, suitable for “click on demand” attachment of antibacterial compounds enabled via incorporation of an alkyne-containing diol monomer in the polymer backbone, is described. By employing different polyolic polytetrahydrofurans, isocyanates, and chain extenders, a robust and flexible material comparable to commercial thermoplastic polyurethane is prepared. A series of short synthetic antimicrobial peptides are designed, synthesized, and covalently attached in a single coupling step to generate a homogenous coating. The lead material is shown to be biocompatible and does not display any toxicity against either mouse fibroblasts or reconstructed human epidermis according to ISO and OECD guidelines. The repelling performance of the peptide-coated materials is illustrated against colonization and biofilm formation by Staphylococcus aureus and Staphylococcus epidermidis on coated plastic films and finally, on coated commercial central venous catheters employing LIVE/DEAD staining, confocal laser scanning microscopy, and bacterial counts. This study presents the successful development of a versatile and scalable polyurethane with the potential for use in the medical field to reduce the impact of bacterial biofilms. 

Background: Airborne bacteria present in the operating room may be a cause of surgical site infection, either contaminating the surgical wound directly, or indirectly via e.g. surgical instruments. The aim of this study was to evaluate if instrument and assistant tables equipped with local unidirectional airflow reduce bacterial contamination of the instrument area to ultra clean levels, during orthopedic implant surgery in an operating room with displacement ventilation. Methods: Local airflow units of instrument and assistant tables were either active or inactive. Colony forming units were sampled intraoperatively from the air above the instruments and from instrument dummies. A minimum of three air samples and two-three samples from instrument dummies were taken during each surgery. Samples were incubated on agar for total aerobic bacterial count. The mean air and instrument contamination during each surgery was calculated and used to analyze the difference in contamination depending on use of local airflow or not. All procedures were performed in the same OR. Results: 188 air and 124 instrument samples were collected during 48 orthopedic implant procedures. Analysis showed that local unidirectional airflow above the surgical instruments significantly reduced the bacterial count in the air above assistant table (P<0.001) and instrument table (P=0.002), as well as on the instrument dummies from the assistant table (P=0.001). Conclusions: Instrumentation tables equipped with local unidirectional airflow protect the surgical instruments from bacterial contamination during orthopedic implant surgery and may therefore reduce the risk of indirect wound contamination. © 2022 The Authors

A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged β-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G' = 0.5-8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.

Dispersions of cubic liquid crystalline phases, also known as cubosomes, have shown great promise as delivery vehicles for a wide range of medicines. Due to their ordered structure, comprising alternating hydrophilic and hydrophobic domains, cubosomes possess unique delivery properties and compatibility with both water-soluble and -insoluble drugs. However, the drug delivery mechanism and cubosome interaction with human cells and bacteria are still poorly understood. Herein, we reveal how cubosomes loaded with the human cathelicidin antimicrobial peptide LL-37, a system with high bacteria-killing effect, interact with the bacterial membrane and provide new insights into the eradication mechanism. Combining the advanced experimental techniques neutron reflectivity and quartz crystal microbalance with dissipation monitoring, a mechanistic drug delivery model for LL-37-loaded cubosomes on bacterial mimicking bilayers was constructed. Moreover, the cubosome interaction with Escherichia coli was directly visualized using super-resolution laser scanning microscopy and cryogenic electron tomography. We could conclude that cubosomes loaded with LL-37 adsorbed and distorted bacterial membranes, providing evidence that the peptide-loaded cubosomes function as an antimicrobial unit.

Both pathogenic bacteria and fungi are developing resistance to common antimicrobial treatment at an alarming rate. To counteract this development, it is of essence to develop new classes of antimicrobial agents. One such class is antimicrobial peptides, most of which are derived from the innate immune system. In this study, a series of novel 2,5-diketopiperazines were designed, synthesized, and evaluated for their antimicrobial abilities. The compounds were designed to probe the pharmacophore dictated for short linear mimics of antimicrobial cationic peptides, and as such, the compounds contain a range of cationic and hydrophobic functionalities. Several of the prepared compounds displayed high antimicrobial activities toward bacteria and also against human pathogenic fungi. Of particular interest was the high activity toward fungal strains with an inherent increased resistance toward conventional antifungal agents. The most effective compounds displayed inhibition of Candida glabrata and Candida krusei growth at concentrations between 4 and 8 μg/mL, which is comparable to commercial antifungal agents in use. Structure activity relationship studies revealed a similar dependence on cationic charge and the volume of the hydrophobic bulk as for linear cationic antimicrobial peptides. Finally, the hemolytic activity of selected compounds was evaluated, which revealed a potential to produce active compounds with attenuation of unwanted hemolysis. The findings highlight the potential of cyclic cationic amphiphilic peptidomimetics as a class of promising compounds for the treatment of infections caused by microorganisms with an increased resistance to conventional antimicrobial agents. © 2018 European Peptide Society and John Wiley & Sons, Ltd.

Background: With the rising demand for osseointegrated titanium implants for replacing missing teeth, often in patients with a history of periodontitis, implant-related infections have become an issue of growing concern. Novel methods for treating and preventing implant-associated infections are urgently needed. The aim of this study was to investigate if different pH, atmosphere and surface properties could restrict bacterial adhesion to titanium surfaces used in dental implants. Methods: Titanium discs with machined or anodized (TiUnite™) surface were incubated with a co-culture of Streptococcus mitis and Actinomyces oris (early colonizers of oral surfaces) at pH 5.0, 7.0 and 9.0 at aerobic or anaerobic atmosphere. The adhesion was analysed by counting colony forming (CFU) units on agar and by confocal laser scanning microscopy (CLSM).Results: The CFU analysis showed that a pH of 5.0 was found to significantly decrease the adhesion of S. mitis, and an aerobic atmosphere, the adhesion of A. oris. S. mitis was found in significantly less amounts on the anodized surface than the machined surface, while A. oris was found in equal amounts on both surfaces. The CLSM analysis confirmed the results from the CFU count and provided additional information on how the two oral commensal species adhered to the surfaces: mainly in dispersed clusters oriented with the groves of the machined surface and the pores of the anodized surface. Conclusions: Bacterial adhesion by S. mitis and A. oris can be restricted by acidic pH and aerobic atmosphere. The anodized surface reduced the adhesion of S. mitis compared to the machined surface; while A. oris adhered equally well to the pores of the anodized surface and to the grooves of the machined surface. It is difficult to transfer these results directly into a clinical situation. However, it is worth further investigating these findings from an in vitro perspective, as well as clinically, to gain more knowledge of the effects acid pH and aerobic atmosphere have on initial bacterial adhesion.