Mechanically robust and highly hydrated curcumin-loaded lysine-crosslinked carboxymethyl cellulose hydrogels for steroid-free atopic dermatitis treatment

Carboxymethyl cellulose (CMC) exhibits excellent biocompatibility and water retention, yet its high hydrophilicity often leads to excessive swelling and poor mechanical stability in physiological environments, limiting its utility in topical skin therapies. In this study, we developed a robust, chemically crosslinked CMC-based hydrogel loaded with curcumin (Cur@CL) using natural lysine as a non-toxic crosslinker. This green crosslinking strategy significantly reinforced the hydrogel network, achieving a swelling ratio of 3074 ± 226% and a compressive stress of 20.06 ± 1.0 kPa. The Cur@CL hydrogel demonstrated a sustained curcumin release profile of 83.98 ± 5.68% over 144 h, ensuring prolonged local bioavailability. In vitro, Cur@CL exhibited excellent cytocompatibility with L929 fibroblasts, accelerated fibroblast-associated wound closure, and reduced intracellular reactive oxygen species (ROS) levels by 62.97%. Furthermore, in a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) mouse model, topical application of Cur@CL significantly alleviated clinical symptoms, reducing epidermal thickening by 71.5% compared with the DNCB-challenged model group, with no detectable systemic toxicity. This study presents a simple, tunable, and eco-friendly cellulose-based hydrogel platform for the effective, non-steroidal management of AD.