Functionalized Silk Fibroin and Mucin Hybrid Material for Targeted EGF and Papain Delivery in Wound Healing

Silk fibroin (SF) and mucin are extensively recognized as promising biomaterials for wound dressings due to their outstanding biocompatibility, biodegradability, and ability to support cell growth and tissue regeneration. In this study, we developed a hybrid SF/mucin wound dressing (HYB) using tetrazine and norbornene click chemistry to enhance its structural and functional properties. The robust assembly resulted in a dual-phase material with a dense SF membrane and a porous mucin hydrogel (MH). Scanning electron microscopy confirmed the successful integration and tight adhesion between these polymers. The hybrid material exhibited a controlled release of bioactive agents, with epidermal growth factor (EGF) showing a sustained release of up to 48% over 48 h. The optimized 25 mg/mL mucin hydrogel showed efficient EGF release and performance comparable to higher concentrations. It was selected for papain loading to reduce material usage without compromising efficacy. HYB showed a higher papain release rate of 36% compared to the bare SF membrane. Additionally, the hybrid material exhibited enhanced mechanical strength, optimized water vapor permeability comparable to commercial wound dressings, and improved cell proliferation relative to its individual components. Cytotoxicity assays demonstrated that the papain-loaded hybrid material is a viable candidate for wound dressing applications. These results suggest that the click-chemistry-functionalized SF/mucin hybrid material holds significant potential as an advanced wound dressing, capable of promoting tissue regeneration while maintaining a moist environment conducive to healing.