Antimicrobial Platforms for Combating Multidrug-resistant Bacteria in Wounds

Abstract

Chronic wounds are a major issue in public health. One of the contributing factors in the development of chronic wounds is bacterial infection, which is exacerbated by the presence of multidrug-resistant (MDR) bacteria. One approach to tackle wound infection is the use of non-antibiotic antimicrobials with rapid killing effect without inducing resistance. This thesis aims to investigate the application of antimicrobial polymers and iodine in the development of antimicrobial wound dressing platforms. Firstly, contact-active antimicrobial wound dressings were explored. An inert silk sponge was prepared as the substrate and functionalized with antimicrobial polymers on the surface via layer-by-layer assembly. Electrostatic interactions in the multilayer construct confined the antimicrobial polymers and prevented leaching. The sponge was able to suck bacteria into the porous network and kill them upon contact as evidenced by up to 4 log10 reduction against Gram-negative and Gram-positive bacteria. Additionally, the antimicrobial efficacy was found to be strongly affected by the construction of multilayer assembly. As the contact-active mechanism may reach saturation point on the surface, in the second approach, an antimicrobial platform with a release-killing mechanism was developed. Employing the ability of silk to self-assemble into a thin film, antimicrobial polymers were loaded in the silk matrix. The release of antimicrobial polymers correlated to polymer concentration, silk to polymer ratio, and film configuration. The efficacy of the films was demonstrated by 5 to 7 log10 reduction of planktonic and 3 to 7 log10 reduction of biofilm cells against Pseudomonas aeruginosa and Staphylococcus aureus, including MDR strains. Furthermore, the straightforward coating method was as effective on glass or cotton substrates. The third approach investigated the immobilization of iodine onto wound dressings for a sustained release system. The immobilization was facilitated by polyamide iodophors that were synthesized on the dressing via plasma polymerization of the gaseous amide monomers. The antimicrobial activity correlated strongly to the structure of the polyamide with the short and linear polymer recorded 4 log10 reduction against P. aeruginosa and 7 log10 reduction S. aureus, including a MDR strain. Overall, the immobilization of iodophors on wound dressings demonstrated a potential new approach in reducing bacteria proliferation in wounds.