Bio-Inspired Adhesive Hydrogels for Localized Therapeutic Delivery: From Catechol Chemistry to Smart Biointerfaces

Localized therapeutic delivery has gained increasing attention as an effective strategy in enhancing treatment efficacy while at the same time minimizing systemic side effects. However, conventional hydrogel-based therapeutic delivery systems often suffer from poor tissue retention and insufficient control over delivery. This drawback is highly pronounced in wet and dynamic biological environments. So, catechol-based adhesive hydrogels have emerged as promising biomaterials for localized therapeutic applications and are inspired by the remarkable wet-adhesion capability of marine mussels. As a highlight, catechol chemistry enables robust tissue adhesion through multiple intermolecular interactions, including hydrogen bonding, metal coordination, and covalent coupling. At the same time, it contributes to hydrogel cohesion and structural stability. Recent advances in hydrogel engineering have expanded the functionality of these systems through integration of injectable formulations, self-healing networks, nanocomposite reinforcement, and stimuli-responsive biointerfaces. These developments have transformed adhesive hydrogels from tissue sealants into multifunctional therapeutic platforms capable of enhancing tissue retention, regulating therapeutic release, and dynamically interacting with biological microenvironments. Here, we review molecular mechanisms underlying catechol-mediated adhesion and discuss recent progress in advanced adhesive hydrogel systems. We further highlight their therapeutic applications in wound healing, musculoskeletal regeneration, exosome and gene delivery, immunomodulatory therapies, and localized cancer therapy. Finally, current translational challenges and future opportunities in developing next-generation smart biointerfaces for precision regenerative medicine are discussed.