Next-generation antimicrobial dermal matrix eradicates polymicrobial biofilms and modulates inflammation in in vitro and ex vivo wound models

Recent technological advances have highlighted the potential of antimicrobial peptides (AMPs) as promising alternatives to conventional antibiotics in combating the overwhelming rise of antimicrobial resistance (AMR) in wound care. In this study, two AMPs, Nisin and cathelicidin LL-37 AMPs were for the first time coated together onto a commercially available dermal substitute, NovoSorb Biodegradable Temporising Matrix (BTM), to develop a next-generation antimicrobial dermal substitute (BTM-AMPs). In vitro results demonstrated strong antimicrobial activity of the BTM-AMPs, with an ability to eradicate mature polymicrobial biofilms consisting of common Gram-positive and Gram-negative pathogens. In a direct contact kill assay, BTM-AMPs showed a comparable efficacy to the commercially available antimicrobial matrix, Endoform. Using an ex vivo bioluminescent biofilm model, BTM-AMPs reduced the burden of metabolically active bacteria by > 50% after 6 h of treatment. Furthermore, BTM-AMPs exhibited strong anti-inflammatory properties by significantly reducing the level of pro-inflammatory TNF-α cytokine and increasing the phagocytotic activity of macrophages in vitro. Overall, dual coating of Nisin and LL-37 onto the BTM dermal substitute presents a promising approach for managing clinical infections and eradicating biofilms in chronic wounds.