Regenerative Performance and Structural Persistence of Silk Fibroin Matrices in Human Infected and Non-Infected Ex Vivo Wounds

Biodegradable biomaterials are promising candidates for regenerative wound care, yet their performance under infection-driven conditions remains poorly understood. This study evaluated the regenerative efficacy and structural persistence of a silk fibroin membrane and electrospun nonwoven matrix using a human ex vivo full-thickness skin wound model under non-infected and bacterially infected conditions. Complementary in vitro degradation assays assessed matrix durability following exposure to Staphylococcus aureus, Pseudomonas aeruginosa, bacterial culture supernatants and clinically relevant antiseptic solutions. In non-infected wound conditions, both matrices enhanced wound regeneration, resulting in increased re-epithelialization and proliferative activity compared with untreated controls; membrane-treated wounds achieved approximately 95% re-epithelialization after 15 days compared with approximately 20% in untreated controls, indicating accelerated wound closure, whereas nonwoven matrices supported sustained cellular proliferation over time. In contrast, bacterial infection was associated with almost complete absence of re-epithelialization and proliferative activity irrespective of matrix architecture. Matrix persistence was pathogen-dependent. While S. aureus induced moderate degradation, P. aeruginosa caused pronounced structural deterioration in ex vivo and in vitro models. Exposure to P. aeruginosa culture supernatants produced similar effects. These findings demonstrate that regenerative efficacy and material persistence are distinct biomaterial properties that are strongly influenced by the wound microbiological environment and are profoundly compromised under conditions of high bacterial burden.