Fermentation-integrated In Situ functionalization of bacterial cellulose with Coptis chinensis and pomegranate peel extracts for antibacterial wound healing.

Abstract

Infected wound treatment requires multifunctional biomaterials to combat infection, oxidative stress, and impaired tissue repair. Bacterial cellulose (BC) provides a hydrated nanofibrous scaffold for wound dressings; however, its functionalization often suffers from inefficient incorporation of poorly water-dispersible bioactives and harsh purification procedures. Here, we developed a fermentation-integrated strategy that combines the submerged BC-forming capability of Kosakonia oryzendophytica FY-07 with xanthan-gum-assisted dispersion of plant-derived bioactives and temperature-triggered bacterial autolysis for in situ fabrication of functional BC composites. Alkaloid-rich Coptis chinensis extract and polyphenol-rich pomegranate peel extract were incorporated during BC biosynthesis, followed by mild enzymatic purification. The resulting membranes achieved high bioactive incorporation efficiencies of 89.73% and 94.61%, respectively, and exhibited sustained release behavior. The incorporated bioactives endowed BC membranes with enhanced antioxidant and antibacterial activities, while maintaining favorable cytocompatibility and hemocompatibility. In particular, the pomegranate peel extract-incorporated membrane showed strong radical-scavenging capacity, achieving DPPH• and ABTS•+ scavenging rates of 97.64% and 95.22%, respectively. Moreover, the engineered FY-07 strain enabled temperature-triggered autolysis, resulting in an approximately 5.1-log reduction in viable cells and facilitating mild downstream purification. In a Staphylococcus aureus-infected full-thickness wound model, the composite membranes effectively promoted wound healing. This work establishes a fermentation-integrated manufacturing platform that couples microbial BC production with in situ incorporation and controlled delivery of natural bioactives, providing a sustainable approach for the fabrication of multifunctional BC-based wound biomaterials.