Targeted Antibacterial Endolysin to Treat Infected Wounds on 3D Full-Thickness Skin Model: XZ.700 Efficacy

<b>Backgrounds/Objectives:</b> Skin wound healing is a physiological process orchestrated by epithelial and mesenchymal cells able to restore tissue continuity by re-organizing themselves and the ECM. This research study aimed to develop an optimized in vitro experimental model of full-thickness skin, to address molecular and morphological modifications occurring in the re-epithelization and wound healing process. <b>Methods:</b> Wound healing starting events were investigated within an experimental window of 8 days at the molecular level by gene expression and immunofluorescence of key epidermal and dermal biomarkers. To mirror the behavior of infected wounds, the established wound healing model was then colonized with <i>S. aureus</i>, and the efficacy of a novel antibacterial agent, XZ.700, was investigated. Viable counts (CFU/tissue), IF, and ultrastructural analysis (SEM) were performed to evaluate <i>S. aureus</i> colonization inside and around the wound bed in an experimental window of 3 h of colonization and 24 h of treatment. <b>Results:</b> Endolysin showed an efficacy in counteracting bacterial growth and invasion within the wound bed, reducing the <i>S. aureus</i> load compared to its placebo, thanks to its selective antimicrobial activity interfering with biofilm formation. <b>Conclusions:</b> The preclinical in vitro infected wound model on FT-kin showed interesting applications to assess the repair efficacy of dermo-pharmaceutical and cosmetic formulations.