Projektdaten

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Kohlenmonoxid-freisetzende Vliese als innovative antibakterielle Wundauflage

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Medical biofilms are present in over 80% of infections and show strongly increased antibiotic tolerance through a combination of extracellular biofilm matrix, metabolic inactive persister cells and changed microenvironments. Biofilms are inert against the immune system, poorly treatable and nearly impossible to eradicate. Multispecies biofilms including multi-drug resistant organisms (MDRO) are a tremendous therapeutic challenge. Such biofilms involving MDRO can be found in chronic wound infections, particularly in diabetic foot infections, which frequently require amputation. Therefore, therapeutic alternatives to eliminate such biofilms would greatly improve patient care. We focused on a novel strategy that is not affected by known mechanisms of antibiotic resistance, including phenotypic resistance (tolerance) caused by biofilm formation: carbon monoxide (CO). CO is known to have a role in numerous physiological processes, inhibiting key enzymes in the essential electron transport chain leading to cell death. CO in controlled doses has been investigated as a therapeutic agent with anti-inflammatory and cell-protective effects. Carbon monoxide-releasing molecules (CORMs) and among them, transition metal carbonyl complexes are promising novel therapeutics as they can be triggered to release CO in a controlled manner by either light. Our own investigations have shown that a CO-induced antimicrobial activity of CORMs was sufficient to reduce the biofilm-embedded bacteria of methicillin-resistant Staphylococcus aureus (MRSA). We propose to create polylactone fleeces by electrospinning, for example, poly(L-lactide-co-DL-lactide) with the noncovalently embedded CO-releasing molecule [Mn2(CO)10], which release CO by irradiation with light in the wavelength range of 405 to 650. Considering the release kinetics, a CORM wound dressing fleece of 5 cm by 5 cm (25 cm2) would release approximately 2 µmol of CO per mg fleece. However, when used as a bactericidal wound dressing, only a local and limited temporary exposure to CO will be applied. This high local CO concentration can be obtained without systemic toxicity by covering a potential CO-containing fleece wound dressing with a gas-impermeable light-transmitting material. We aim to prove the efficacy and safety of these fleeces in a clinical pilot study. Furthermore, we hypothesize that the controlled release of CO will effectively reduce the number of bacteria within mature biofilms over the course of this CO treatment, and anti-inflammatory effects may increase initiation of wound healing. However, comprehensive studies to translate the potential antimicrobial effects of CORMs into clinical available products are lacking.