Hydrogel effects rapid biofilm debridement with ex situ contact-kill to eliminate multidrug resistant bacteria in vivo

Multi-drug resistance and the refractory character of bacterial biofilms are among the most difficult challenges in infection treatment. Current antimicrobial strategies typically are much more effective for prevention of biofilm formation than for eradication of established biofilms; these strategies also leave dead bacteria and endotoxin in the infection site, which impairs healing. We report a novel hydrogel that eradicates biofilm bacteria by non-leaching-based debridement followed by ex-situ contact-killing (DESCK) away from the infection site. The debridement effect is likely due to the high water swellability and microporosity of the crosslinked network which is made from polyethylene glycol dimethacrylate tethered with a dangling polyethylenimine (PEI) star copolymer. The large pore size of the hydrogel makes the cationic pore walls highly accessible to bacteria. The hydrogel also degrades in the presence of infection cells, releasing star cationic PEI into the infection site to contact-kill bacteria remaining there. DESCK hydrogel effectively kills (>99.9% reduction) biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CR-PA) and Acinetobacter baumannii (CR-AB) in a murine excisional wound infection model. Silver-based wound dressings (controls) showed almost no killing of CR-PA and MRSA biofilms. This DESCK hydrogel greatly reduces the bioburden and inflammation, and promotes wound healing. It has great potential for diverse infection treatment applications.MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Accepted versio

Hydrogel Effects Rapid Biofilm Debridement with ex situ Contact-Kill to Eliminate Multidrug Resistant Bacteria in vivo

Multidrug resistance and the refractory character of bacterial biofilms are among the most difficult challenges in infection treatment. Current antimicrobial strategies typically are much more effective for prevention of biofilm formation than for eradication of established biofilms; these strategies also leave dead bacteria and endotoxin in the infection site, which impairs healing. We report a novel hydrogel that eradicates biofilm bacteria by non-leaching-based debridement followed by ex situ contact-killing (DESCK) away from the infection site. The debridement effect is likely due to the high water swellability and microporosity of the cross-linked network which is made from polyethylene glycol dimethacrylate tethered with a dangling polyethylenimine (PEI) star copolymer. The large pore size of the hydrogel makes the cationic pore walls highly accessible to bacteria. The hydrogel also degrades in the presence of infection cells, releasing star cationic PEI into the infection site to contact-kill bacteria remaining there. DESCK hydrogel effectively kills (>99.9% reduction) biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CR-PA) and Acinetobacter baumannii in a murine excisional wound infection model. Silver-based wound dressings (controls) showed almost no killing of CR-PA and MRSA biofilms. This DESCK hydrogel greatly reduces the bioburden and inflammation and promotes wound healing. It has great potential for diverse infection treatment applications

Antimicrobial effect of a novel chitosan derivative and its synergistic effect with antibiotics

Cationic polymers are promising antibacterial agents since they have a low propensity for bacteria to evolve resistance, but they usually have low biocompatibility due to their hydrophobic moieties. Herein, we report a new biodegradable and biocompatible chitosan-derived cationic antibacterial polymer, 2,6-Diamino Chitosan (2,6-DAC). 2,6-DAC shows excellent broad-spectrum antimicrobial activity with minimum inhibitory concentrations (MICs) of 8-32 µg/mL against clinically relevant and multi-drug resistant (MDR) bacteria including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Further, 2,6-DAC shows an excellent synergistic effect with various clinically relevant antibiotics proved by decreasing the MICs of the antibiotics against MDR A. baumannii and MRSA to 2.4 log10 reduction of A. baumannii in murine intraperitoneal and lung infection models. The novel chitosan derivative, 2,6-DAC, can be utilized as biocompatible broad-spectrum cationic antimicrobial agent alone or in synergistic combination with various antibiotics.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Ministry of Health (MOH)Nanyang Technological UniversityAccepted versionWe thank the funding support from Singapore Ministry of Education Tier 3 grants (MOE2013-T3-1-002, MOE2018-T3-1-003), a Singapore Ministry of Health Industry Alignment Fund (NMRC/ MOHIAFCAT2/003/2014) and NTU. We also thank the ASTAR Wound Care Innovation for the Tropics IAF-PP (HBMS Domain) with grant number H17/01/a0/0M9, and ASTAR RIE2020 Advanced Manufacturing and Engineering (AME) IAP-PP Specialty Chemicals Programme (Grant No. A1786a0032). We also thank the Major Project of 2025 Sci&Tech Innovation of Ningbo (2018B10052) and NSF of China, 8147179