Silk-Fibroin-Based Adhesive Hydrogels: Mechanistic Insights and Biomedical ApplicationsA Review

Hydrogels are versatile soft materials extensively applied in biomedical fields including tissue engineering, drug delivery, and biosensing. A critical challenge in these applications is maintaining hydrogel integrity at the target site, as the loss or displacement of the hydrogel can compromise tissue regeneration, therapeutic delivery, or sensor functionality. Adhesive hydrogels, therefore, are essential to ensure stable interfacial interactions with biological tissues. Silk fibroin, a natural polymer, offers biocompatibility, low toxicity, tunable mechanical properties, and controllable biodegradability, making it a promising candidate for hydrogel scaffolds and biosensor substrates. However, its limited functional sites restrict intrinsic adhesion, necessitating strategies to enhance interfacial bonding. This Review systematically examines approaches to improve the adhesion of silk-fibroin-based hydrogels, including chemical modification, incorporation of functional polymers, and catechol-mediated interactions, alongside the mechanistic principles underlying each strategy. Representative applications in tissue engineering, drug delivery, and biosensing are highlighted to demonstrate their translational potential. By integration of design strategies with mechanistic insights, this work provides a framework for developing silk-fibroin-based adhesive hydrogels tailored for specific tissue interfaces, enabling robust, multifunctional, and clinically relevant biomaterials for advanced biomedical and diagnostic applications.