Adhesive Hydrogels in Orthopedic Therapy: Design Strategies, Functional Innovations, and Clinical Translation.

The musculoskeletal system, essential for mobility, structural support, and organ protection, is frequently compromised by trauma, degenerative diseases, or tumors, profoundly impacting patients' quality of life. Adhesive hydrogels have emerged as pivotal biomaterials for orthopedic therapies, offering localized treatment with enhanced biocompatibility, tunable mechanics, and sustained bioactive delivery. While systemic drug administration often suffers from off-target effects, adhesive hydrogels enable precise tissue integration and microenvironmental modulation, addressing challenges such as infection control, tissue regeneration, and mechanical reinforcement. However, achieving optimal adhesion strength, dynamic mechanical matching, and selective tissue targeting remains a critical hurdle. Innovative strategies, including dynamic covalent bonds, stimuli-responsive networks, and multifunctional hybridization, have expanded hydrogel applications in diabetic wound healing, load-bearing bone repair, and spinal cord regeneration. For instance, injectable hydrogels with wet adhesion capabilities facilitate minimally invasive delivery, while drug-eluting systems localize chemotherapeutics to tumor sites, reducing systemic toxicity. Despite these advances, scalability, long-term stability, and clinical translation require further exploration. This review systematically examines the design principles, functional mechanisms, and therapeutic applications of adhesive hydrogels in orthopedics, emphasizing their role in bridging biomechanical demands with biological regeneration. We envision that interdisciplinary innovation in smart hydrogels will unlock personalized solutions, transforming the landscape of precision orthopedic medicine.