Antigen-specific IgY as an orally deliverable biomaterial for sustained immunomodulation in ulcerative colitis.

Over the past decades, antibodies have become indispensable tools due to their high specificity and versatility. Egg yolk antibody (IgY), a natural protein biomaterial noted for its biosafety, thermal stability, and cost-effective, is particularly suitable for long-term interventions in chronic diseases. Its intrinsic biocompatibility allows safe oral administration, while its structural robustness facilitates diverse delivery formats such as bioactive formulations or coatings. This makes IgY a promising candidate for managing conditions like inflammatory bowel disease (IBD), including ulcerative colitis (UC), which require prolonged, well-tolerated therapeutic strategies. However, the antigen-specific therapeutic potential of IgY in IBD remains underexplored. Here, we propose to use an engineered anti-TNFR1 IgY as an oral therapeutic agent for UC intervention as a TNFR1-selective strategy. Anti-TNFR1 IgY exhibited superior gastrointestinal stability to mammalian IgG and suppressed the production of key inflammatory mediators, such as IL-6 and MMP9, in stimulated RAW264.7 macrophages. In a DSS-induced murine colitis model, oral administration of anti-TNFR1 IgY significantly alleviated inflammation, evidenced by reduced biomarkers (calprotectin, IL-6, TNF-α) and elevated IL-10, alongside improved behavioral manifestations and attenuated histopathological staining. Moreover, it retained bioactivity following heating, freeze-drying, and hydrogel encapsulation, supporting its potential as a scalable robust bioactive building block. Our work highlights antigen-specific IgY as a biocompatible biomaterial-based strategy for long-term immunomodulation in intestinal inflammation. This platform may help connect orally administered targeted therapy with gastrointestinal health management.