A Synergistic Hydrogel Strategy for the Treatment of Candida Vaginitis Through Pathogen Clearance and Microecosystem Restoration

ABSTRACT Microbial infections often disrupt the delicate balance of host commensal microbiota, leading to dysbiosis and recurrent infections, yet current therapies lack the capacity to simultaneously eradicate pathogens and restore ecological homeostasis. Here, we report a synergistic therapeutic strategy for Candida vaginitis that integrates targeted pathogen clearance with vaginal microecosystem restoration. We engineer a vaginal microenvironment‐degradable hydrogel, HCS/FUC@Lab PC , which self‐assembles from highly deacetylated high molecular‐weight chitosan oligosaccharide (HCS) and fucoidan (FUC) to encapsulate Lactobacillus (Lab) coated with procyanidine (PC). Within the vaginal microenvironment, the hydrogel gradually degrades and releases HCS, which efficiently eliminates Candida albicans ( C. albicans ) by disrupting cell wall integrity and interfering MAPK related signaling. FUC and PC further contribute to microenvironmental remodeling through their intrinsic anti‐inflammatory and antioxidant activities. This remodeling facilitates stable colonization of Lab, which subsequently reinforces barrier integrity through competitive exclusion and metabolic modulation. In murine models, this approach effectively disrupts the infection–dysbiosis–recurrence vicious cycle, supporting an integrated therapeutic strategy that combines pathogen clearance, microenvironmental remodeling, and microecosystem restoration.