Nisin and LL-37 dual-coated dermal matrix eradicates polymicrobial biofilms and modulates inflammation in wound models

Effective management of infected chronic wounds remains a significant clinical challenge, largely due to the overwhelming rise of antimicrobial resistance (AMR). Conventional antibiotics are increasingly compromised, necessitating novel therapeutic strategies. Antimicrobial peptides (AMPs), such as Nisin and cathelicidin LL-37, offer promising alternatives due to their broad-spectrum activity and diverse mechanisms. However, their clinical translation is often hindered by poor stability and delivery challenges, creating a critical gap for stable, effective AMP delivery systems in wound care.

Researchers developed a next-generation antimicrobial dermal substitute by dual-coating two AMPs, Nisin and cathelicidin LL-37, onto a commercially available dermal substitute, NovoSorb Biodegradable Temporising Matrix (BTM), creating BTM-AMPs. The antimicrobial activity of BTM-AMPs was assessed in vitro against mature polymicrobial biofilms comprising common Gram-positive and Gram-negative pathogens. Efficacy was compared to the commercially available antimicrobial matrix, Endoform, in a direct contact kill assay. An ex vivo bioluminescent biofilm model was used to quantify metabolically active bacteria, and in vitro assays measured pro-inflammatory TNF-α cytokine levels and macrophage phagocytotic activity.

The BTM-AMPs demonstrated strong antimicrobial activity, effectively eradicating mature polymicrobial biofilms composed of both Gram-positive and Gram-negative pathogens in vitro. In direct contact kill assays, the BTM-AMPs showed comparable efficacy to the commercially available antimicrobial matrix, Endoform. Using an ex vivo bioluminescent biofilm model, the BTM-AMPs significantly reduced the burden of metabolically active bacteria by >50% after just 6 h of treatment. Beyond antimicrobial effects, the BTM-AMPs also exhibited robust anti-inflammatory properties. > They significantly reduced the level of the pro-inflammatory TNF-α cytokine and notably increased the phagocytotic activity of macrophages in vitro. These dual actions highlight the potential for comprehensive wound management.