A Bioactive PLGA-modified SIS scaffold loaded with astragaloside IV-preconditioned BMSCs promotes infected wound healing.

Infected wounds present a significant clinical challenge due to persistent inflammation, bacterial infection, and hindered tissue regeneration. In this study, we developed a composite bioactive scaffold by combining PLGA-modified small intestinal submucosa (SIS) with astragaloside IV (AS-IV)-preconditioned bone marrow mesenchymal stem cells (BMSCs). We evaluated its physicochemical characteristics and therapeutic effectiveness both in vitro and in a infected wound model. The composite scaffold exhibited enhanced mechanical strength and facilitated the adhesion and proliferation of the BMSCs. Pretreatment with AS-IV significantly enhanced BMSC survival and boosted the secretion of pro-regenerative factors such as VEGF and TGF-β, potentially contributing to the observed enhanced regenerative effects in this study. In vivo, the PABS group exhibited markedly accelerated wound closure compared to the control groups, along with reduced infiltration of inflammatory cells and increased collagen deposition (~ 50%) and epidermal thickness (~ 154 μm). Furthermore, enhanced angiogenesis and controlled expression of inflammatory cytokines (reduced TNF-α, IL-1β, and IL-6; increased IL-10) were observed, suggesting a potentially improved modulation of the wound microenvironment. This multifunctional scaffold facilitated wound healing by combining antibacterial, anti-inflammatory, and pro-regenerative effects, offering a promising approach for managing chronic and infected wounds.