(LR-053) Novel antibiotic-free Synthetic Wound Matrix with potent broad-spectrum antimicrobial, antibiofilm efficacy and superior healing outcomes

Bishnu Joshi, PhD – Senior Scientist, Biomaterials, Gel4Med, Inc.; Manav Mehta, PhD – CEO, Gel4Med, Inc.; Crystal Hardy, B.S. – Senior Scientist, Microbiology, Gel4Med, Inc.; Eliza Hoobler, Bachelor's Degree – Research Associate, Gel4Med, Inc.; Priyanka Thakor, M.S. – Manager of Quality and CMC, Gel4Med, Inc.

Introduction: Pathogenic colonization is a major risk factor for acute and chronic wound complications. The rise of multidrug-resistant organisms (MDROs) and biofilms further complicates treatment and increases the burden of infected wounds. To address this growing problem, we have developed a first-in-class Biosynthetic Wound Matrix (SWM) to promote infection-free wound closure. SWM provides unique broad-spectrum antimicrobial mechanism of action that evades microbial resistance, stably-degrading scaffolding matrix for tissue regrowth, and wound-conforming properties for easy administration and complete cavity filling.

Methods: Standard suspension time-kill assay was used to test antimicrobial effectiveness 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). Efficacy against 72h-aged biofilms (PaO1 ± MRSA) was evaluated in vitro and ex vivo(pig skin). In mice, MRSA-inoculated wounds were treated with SWM or silver gel, then assessed by bioluminescence imaging and microbiology. In a swine model of full-thickness wounds, SWM wound healing efficacy was evaluated vs. silver and collagen-based gels.

Results: In vitro, SWM rapidly eliminated ≥6 log₁₀ CFU of Gram-positive and Gram-negative bacteria, sporulating and non-sporulating fungal pathogens, and mature PaO1 and MRSA biofilms. Mature PaO1 biofilms in pig skin explants were eradicated by single application. SWM reduced bioburden in inoculated murine full-thickness wounds by 6h, outperforming silver and sustaining efficacy for 72h against high doses of bacteria (10⁶ CFU/wound). At day 14, swine full-thickness wounds treated with SWM showed the greatest closure (96%, n≥4). SWM singularly achieved complete re-epithelialization and healthy granulation tissue repletion.

Discussion: Current wound products have serious limitations: antimicrobials are ineffective against MDROs and biofilms, and inhibit tissue regrowth; skin substitutes are prone to colonization and contraindicated in infected wounds; sheet forms are not amenable for cavity wounds. Easy-to-use and cost effective, SWM has the potential to overcome these challenges by uniquely combining key properties: flowable to completely fill complex and cavity wound voids, scaffolding matrix with cell attachment sites to encourage tissue regeneration, controlled biodegradation in hostile proteolytic environments, and broad-spectrum antimicrobial activity (including against MDROs). SWM is anticipated to become clinically available in Q2 2023.