Engineered Sulfonated Bacterial Cellulose Hydrogel with Dual Bioactive-Drug Delivery Functions for Precision Treatment of Psoriasis.

Psoriasis is a chronic, inflammatory skin disorder driven by dysregulated keratinocyte-immune interactions and oxidative stress. To address limitations of conventional therapies, we engineered a sulfated bacterial cellulose/chitosan hydrogel that integrates intrinsic bioactivity with controlled methotrexate delivery (MTX-SBC/CS Gel). Sulfonation introduced sulfonic groups, conferring potent ROS-scavenging activity while optimizing drug compatibility and release kinetics. Chitosan enabled self-healing and bioadhesion through hydrogen-bonding networks. Molecular simulations and experiments revealed how sulfonic groups modulate drug-polymer interactions. In imiquimod-induced psoriatic models, MTX-SBC/CS Gel exhibited therapeutic efficacy comparable to that of the clinical standard betamethasone, with SBC alone showing beneficial effects; both accelerated epidermal normalization, and cytokine suppression. Transcriptomics identified SBC's multimodal mechanism: downregulation of IL-23/Th17 axis components, inhibition of keratinocyte hyperproliferation, and restoration of redox homeostasis via HSP90α-mediated pathways. The synergistic integration of sulfonation-enabled ROS scavenging, and optimized MTX release kinetics establishes this engineered hydrogel as a promising platform for the management of dermatoses.