Carolina V. Delgado-Gazzoni

Chronic wounds are frequently complicated by biofilm-associated infections that impair healing and limit treatment efficacy. Buddleja globosa (BG) exhibits antimicrobial and regenerative properties, making it a promising candidate for advanced wound care. This study aimed to optimize the concentration of a standardized BG extract incorporated into polymeric scaffolds for the treatment of wounds infected with the dual-species biofilm (DSB) of Pseudomonas aeruginosa and Staphylococcus aureus. Scaffolds containing increasing BG concentrations (BG1 to BG4) were fabricated by lyophilization and characterized in terms of physicochemical properties, antimicrobial activity, and cytocompatibility. Their therapeutic efficacy was further evaluated using an in vitro artificial wound model and a murine model of a DSB-infected wound. BG incorporation significantly influenced the scaffold properties. While BG1–BG3 maintained a comparable structure and mechanical integrity, BG4 exhibited a reduced pore size, swelling capacity, and mechanical resistance. All BG-loaded scaffolds reduced bacterial viability in vitro, with BG4 showing the strongest antimicrobial effect. In vivo, BG2 showed the most consistent overall performance, combining improved wound closure at day 6 with complete re-epithelialization at the endpoint. BG3 improved wound closure at day 6 but did not outperform it in re-epithelialization. In contrast, BG4 did not enhance healing despite its higher antimicrobial activity in vitro. These findings demonstrate that scaffold performance is governed by the interplay between extract loading and physicochemical properties, and that intermediate BG concentrations provide more favorable conditions for tissue repair than higher loadings. This work supports the potential of BG-loaded scaffolds as a therapeutic strategy for biofilm-infected chronic wounds.