Sustained TNFα Suppression and Enhanced Cutaneous Healing via Topical IgY Hydrogel Therapy in Inflammatory Skin Disorders

With the progression of biomedical therapies, antibodies have emerged as promising agents for treating inflammatory skin disorders due to their specificity and antigen-targeting capabilities. Antibodies play a crucial role in epidermal injury repair by precisely regulating inflammatory pathways and neutralizing key inflammatory factors. Notably, conventional IgG antibodies face limitations including poor stability, immunogenicity, and reduced efficacy in epidermal environments. Therefore, developing an alternative antibody delivery system capable of overcoming these limitations has become a critical issue to address. Egg yolk antibody (IgY), with its unique Fc structure, exhibits excellent thermal stability and biosafety, making it ideal for treating skin and mucosal diseases. Here, this study proposes an innovative topical IgY hydrogel sustained-release system (IgY-Gel) to deliver TNFα-specific IgY (anti-TNFα IgY), which is demonstrated to effectively reduce the levels of inflammatory factors like IL-6 in LPS-stimulated RAW264.7 cells. The system synergizes with thermosensitive chitosan/β-glycerophosphate (CS/β-GP) hydrogels exhibiting controlled-release properties to enhance the proliferation and migration of human umbilical vein endothelial cells (HUVECs) under pro-inflammatory conditions. In addition, this system demonstrates accelerated wound healing in a mouse wound model, with a significantly higher healing rate of 95.7% in the anti-TNFα IgY-Gel group after 14 days, compared to the respective rates of 73.7%, 77.6%, and 81.7% in control, blank-Gel, and ns IgY-Gel groups, respectively. In conclusion, our IgY-Gel system highlights the anti-inflammatory and wound-healing potential of topical IgY therapy. This innovative system promotes the translational application of antibody therapies toward engineered biologics with enhanced efficacy and safety profiles in tissue repair processes.