Bioadhesive Hydrogels for Tissue Repair: Design Strategies, Adhesion Mechanisms, and Emerging Applications.

Bioadhesive hydrogels combine tissue-adhesive properties with therapeutic multifunctionality, offering promising solutions for regenerative medicine. This comprehensive review examines the design strategies, fundamental adhesion mechanisms, and clinical applications of these biomaterials. We systematically discuss four primary adhesion mechanisms: physical interactions, chemical adhesion, topological mechanical interlocking, and bioinspired adhesion. Key design parameters, including wet-environment adhesion strength, self-healing capability, injectability, and controlled biodegradability, are analyzed and benchmarked against commercial products. Major material platforms, encompassing catechol-based systems, chitosan derivatives, gelatin/GelMA variants, Polyethylene glycol (PEG)-based adhesives, and multi-network hybrid systems, are evaluated for their adhesive performance and functional integration. Tissue-specific applications spanning wound healing, bone/cartilage repair, soft tissue sealing, vascular repair, and neural regeneration are critically assessed, emphasizing in vivo outcomes and clinical translation barriers. Finally, we discuss emerging frontiers, including artificial intelligence-guided material design, on-demand detachable adhesives, and regulatory pathways. Synthesizing over 140 peer-reviewed references from the past two decades, this review provides a systematic roadmap from fundamental adhesion science toward the clinical implementation of next-generation bioadhesive hydrogels.