(WHS-L3.03) NOVEL ANTIBIOTIC-FREE BIOMIMETIC WOUND MATRIX PROVIDES ANTIMICROBIAL PROTECTION AND SUPERIOR HEALING
Thursday, May 16, 2024
10:30 AM – 11:30 AM East Coast USA Time
Background: Pathogenic colonization is a major risk factor for acute and chronic wound complications. Current approaches have serious limitations, and the rise of multidrug-resistant organisms (MDROs) and biofilms further complicates treatment. To address this growing issue, we developed and tested a polypeptide biomimetic wound matrix (BWM) that prevents infection while promoting healing. This self-assembling cationic nanofiber technology was engineered to offer a mechanism of action that evades microbial resistance, a scaffolding matrix with cell attachment sites that encourage tissue regrowth, and wound-conforming properties for tissue void filling.
Methods: Antimicrobial efficacy against Gram-positive [Enterococcus faecium, Staphylococcus epidermidis, Staphylococcus haemolyticus, MRSA] and Gram-negative [Pseudomonas aeruginosa (PaO1), ESBL Escherichia coli, ESBL Klebsiella pneumoniae, Acinetobacter baumannii] bacteria, as well as fungi [Candida albicans, Aspergillus fumigatus] was tested by standard time-kill assays. Efficacy against 72 hour-aged biofilms (PaO1 ± MRSA) was assessed in vitro and ex vivo (porcine skin). MRSA-inoculated murine wounds were treated with BWM and assessed by microbiology at 24 h. BWM mechanical properties were confirmed by rheology and wound bed coverage. In a swine model of full-thickness excisional wounds, BWM healing efficacy was tested vs. silver and collagen gels using the Tissue Analytics platform and histopathology.
Results: In vitro, BWM demonstrated bactericidal efficacy against ≥6 log10 CFU of PaO1 and MRSA at 5, 10, 15, 30, 60 min, and 24 h (p < 0.0001, n=3). Within 24 h, BWM eliminated ≥6 log10 CFU of Gram-positive and Gram-negative clinical isolates, as well as sporulating and non-sporulating fungal pathogens. Notably, BWM showed superior efficacy against PaO1 and MRSA biofilms when compared to marketed antimicrobial gels (p < 0.0001, n=6), while a single application eradicated mature PaO1 biofilms in pig skin explants by 24 h (n=3). Rapid bioburden reduction was confirmed in MRSA-inoculated murine full-thickness wounds (p=0.02, n=10). In a trypsin proteolysis assay, matrix stability was demonstrated for up to 14 days. BWM-treated swine full-thickness excisional wounds showed superior closure rates (96%, n=5) vs. collagen gel and silver gel (p=0.01) and reduced inflammation. BWM singularly achieved complete re-epithelialization with healthy granulation tissue repletion by day 14.
Conclusions: BWM demonstrates potent broad-spectrum antimicrobial activity against MDROs and biofilms. With controlled biodegradation in a highly proteolytic environment, BWM shows a wound healing profile superior to commercial silver and collagen dressings, including greater closure, increased re-epithelialization, granulation tissue formation, and reduced inflammation. Together, the data supports BWM potential to overcome the current challenges in managing complex and infected wounds.