Autocatalytic Hydrogels Patches Mitigating the Imbalance of Oxidative Stress of Atopic Dermatitis-Induced Inflammatory Skin

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by genetic factors and environmental allergens. Allergens or microbes which penetrate deeper into the skin generally triggers an immune response involving Langerhans cells, which present antigens to naive CD4⁺ T cells, leading to the polarization to T helper 2 (Th2) cells. Th2 cells release cytokines such as IL-4 and IL-13, stimulating B cells, mast cells, and eosinophils. B cells then differentiate into plasma cells, increasing immunoglobulin E (IgE) levels, which activates mast cells. Restimulation by antigens leads to mast cell degranulation and the release of histamine and cytokines, further exacerbating AD symptoms. For chronic symptoms, therapeutic agents like steroids, antihistamines, and antibiotics are used, but long-term use can cause side effects such as hyperglycemia, Cushing syndrome, and sleep disturbances. Thus, there is a need for alternative treatments for AD.<br/>Oxidative stress has been linked to AD development, with reactive oxygen species (ROS) such as hydrogen peroxide (H₂O₂), superoxide anions (O₂^.−), and hydroxyl radicals (OH^.) causing cell damage. ROS activate NF-κB pathways, increasing pro-inflammatory cytokines like IL-1β and TNF-α, leading to further T-cell differentiation, worsening AD symptoms. Therefore, suppressing oxidative stress through ROS scavenging could be a potential AD treatment strategy. Cerium oxide nanoparticles (CeNPs) have been studied for their ROS scavenging properties such as catalase- and SOD-mimicking activities. CeNPs possess catalytic antioxidant properties due to the redox reaction between Ce³⁺ and Ce⁴⁺ oxidation states. Even though CeNPs-embedded hydrogels have been used for therapeutic applications in treating diabetic wounds by scavenging ROS, its application to treat AD has not been explored.<br/>This study reports the development of ROS-scavenging therapeutic hydrogels composed of alginate hydrogel embedded with cerium oxide nanoparticles (CeNPs) for AD treatment. CeNP-embedded alginate hydrogels were fabricated using pH-controlled Ca-crosslinking. These hydrogels demonstrated good mechanical properties, biocompatibility, efficient ROS scavenging capacities, and cytoprotective effects under high oxidative stress. In animal experiments, CeNP-embedded hydrogels applied to AD lesions showed therapeutic efficacy, evidenced by decreased epidermal thickness, reduced DNA oxidation damage, and lowered levels of Th2 cytokines, IgE, and tissue-infiltrated mast cells. These findings suggest that ROS-scavenging hydrogels could serve as effective therapeutic patches for managing and treating AD.