Chronic wounds represent a challenge to wound care professionals consuming a great deal of healthcare resources and, at the same time, reducing patient life quality with increased hospitalization times, heavy pain and eventually sepsis and death. Heavy bacterial colonisation is the main reason for non-healing chronic wounds, consequently wounds are often treated with antibiotics prophylactically, thus leading to unnecessary selection for bacterial resistance. Hence, there is a need for point of care testing (PoCT) devices for the evaluation of infection biomarkers allowing an early and appropriate treatment to reduce the severity of the disease and avoid the chronicity. In the last decade, paper based PoCT devices has showed great potential with the development of cheap and versatile microfluidic and lateral flow devices. These devices incorporate sensing molecules (e.g. enzyme substrates) immobilized in specific spots within the paper platform where they will react with determined biomarkers when the liquid sample flows through the device. Myeloperoxidase (MPO) an enzyme secreted by neutrophils and detected in fluids of infected wounds has been postulated as a suitable biomarker for wound diagnostics. MPO catalyzes the oxidation of chloride ions to hypochlorous acid (HClO), a powerful bactericidal oxidant, using hydrogen peroxide as co-substrate. At the same time, MPO can oxidize a variety of molecules including phenols, quinones, hydrazines and also proteins. Taking advantage of MPO substrate promiscuity, here we present an unexplored system for MPO detection based on enzyme-catalysed oxidative dye polymerization which can be incorporated into paper-based PoCT devices. Visual MPO detection has been achieved through the use of phenylenediamines, a common dye component, which its oxidation byMPO yielded bright coloured products distinguishable from the colour of the wound environment. Using paper strips as model of paper-based lateral flow device, immobilisation of the dye substrate was achieved through in situ interaction of the oxidised coloured product with a polycationic polymer. The colour reaction of the immobilised substrates, detectable by naked eye, responds to the MPO levels present in infected wound fluids. Thus revealing an easy system for incorporation of MPO detection in paper based diagnostic devices.
The emergence of drug-resistance microbial pathogens is creating a worldwide healthcare problem. Nanoparticles have been increasingly used as alternative to the antibiotics. Antimicrobial nanoparticles offers a platform against bacteria, viruses, fungus and protozoa and perform this activity by destroying cell membranes, blocking enzyme pathways, altering microbial cell wall, metabolic pathways and protein, DNA expression and acting on components from the extracellular matrix of biofilms. The advantages of the antimicrobial nanoparticles reside in their different mechanisms of action against pathogens, e.g. oxidative stress, metal ion release, or non-oxidative mechanism, which can occur simultaneously. These mechanisms are less likely to cause the appearance of microbial resistance.
Bacterial biofilms are structured, coordinated communities with distinct architectures and properties. They are ubiquitous in nature and possess the sophisticated ability to rapidly adapt and propagate in a wide variety of habitats. Microbial biofilms are at the root of many chronic and recurrent infections and their formation have been estimated to account for 80 % of all microbial infections currently treated in hospitals. Biofilm can grow on any foreign object inserted into the human body but also in different surfaces of the hospital premises.
In this study, we synthesized hybrid enzyme-metal nanoparticles combining the synergistic activities of different antimicrobial agents. The enzyme in the hybrid nano-entities acts on the extracellular components secreted by the bacterial populations to eliminate and to inhibit the formation of biofilm. On the other hand, the biocidal properties of the nanoparticle are provided by the metal counterpart in the naoparticulate composite. This antimicrobial approach could be applied in the form of coatings on surfaces such as hospital textiles, water treatment membranes and implantable medical devices, ensuring a safer environment for both patients and healthy population.
Drug resistance occurrence is a global healthcare concern responsible for the increased morbidity and mortality in hospitals, time of hospitalisation and huge financial loss. The failure of the most antibiotics to kill Bsuperbugs^ poses the urgent need to develop innovative strategies aimed at not only controlling bacterial infection but also the spread of resistance. The prevention of pathogen host invasion by inhibiting bacterial virulence and biofilm formation, and the utilisation of bactericidal agents with different mode of action than classic antibiotics are the two most promising new alternative strategies to overcome antibiotic resistance. Based on these novel approaches, researchers are developing different advanced materials (nanoparticles, hydrogels and surface coatings) with novel antimicrobial properties. In this review, we summarise the recent advances in terms of engineered materials to prevent bacteria-resistant infections according to the antimicrobial strategies underlying their design.