A Bioactive PLGA-Modified SIS Scaffold Loaded with Astragaloside IV–Preconditioned BMSCs Promotes Infected Wound Healing

Background: Infected wounds remain a major clinical challenge due to persistent inflammation, bacterial colonization, and impaired tissue regeneration. In this study, we developed a novel wound dressing composed of PLGA-modified porcine small intestinal submucosa (SIS) loaded with astragaloside-pretreated bone marrow mesenchymal stem cells (BMSCs). The aim was to enhance antibacterial activity and accelerate wound healing. Methods: PLGA was applied to SIS to improve its mechanical strength and biocompatibility. BMSCs were pretreated with astragaloside to enhance their viability and paracrine function before being incorporated into the composite scaffold. The material’s physicochemical properties, cytocompatibility, and antibacterial activity were evaluated. A Staphylococcus aureus–infected full-thickness skin wound model in rats was used to assess the in vivo healing performance and underlying mechanisms. Results: The PLGA-modified SIS provided a favorable surface for BMSC adhesion and proliferation. Astragaloside pretreatment improved BMSC survival and upregulated the secretion of growth factors such as VEGF and TGF-β. In vivo, the composite dressing significantly accelerated wound closure, reduced inflammatory infiltration, enhanced angiogenesis, and improved collagen remodeling compared with the control groups. Histological and molecular analyses confirmed the modulation of inflammatory cytokines and activation of pro-healing pathways. Conclusions: The PLGA-SIS dressing loaded with astragaloside-pretreated BMSCs effectively promoted infected wound healing through combined antibacterial, anti-inflammatory, and regenerative actions. This strategy represents a promising therapeutic approach for chronic or infected wounds and provides a foundation for future clinical translation in regenerative medicine.