Dual-Network Hydrogel for Atopic Dermatitis: Facile Construction from β-Lactoglobulin and Sustained Delivery of Dihydromyricetin

Atopic dermatitis (AD) is a chronic inflammatory skin disease whose treatment is limited by side effects and poor drug stability. Dihydromyricetin (DHM) shows promise in alleviating skin inflammation, yet effective localized and sustained delivery remains challenging. Herein, a β-lactoglobulin-based dual-network (BDN) hydrogel was developed by exploiting the structural plasticity of β-lactoglobulin monomers (BLGMs) to construct two distinct β-lactoglobulin-based (BLG-based) polymers, with DHM incorporated to obtain the BDN-DHM hydrogel. Photo-cross-linkable glycidyl methacrylate-modified β-lactoglobulin (BLG-GMA) polymers formed an irreversible covalent network, while β-lactoglobulin fibrils (BLGFs) established a dynamic network through Schiff-base reactions with oxidized dextran (ODEX). The resulting BDN-DHM hydrogel exhibited high mechanical strength, sustained drug release, antioxidant activity, and anti-inflammatory effects. In vivo studies further showed alleviation of AD-like symptoms and enhanced skin repair. Overall, the outcomes demonstrate the BDN-DHM hydrogel as a promising local dressing for AD and underscore the potential of BLGMs as versatile building blocks for multifunctional biomaterials.