On-demand degradation: A design principle for next-generation tissue adhesives

Tissue adhesives are a class of biomedical materials that can replace or assist traditional suturing techniques, finding widespread use in wound closure, tissue repair, and drug delivery. Traditional adhesives are primarily limited by their uncontrollable degradation behavior, which fails to synchronize with the dynamic process of tissue regeneration. In recent years, smart tissue adhesives with "on-demand degradation" capabilities have become a research focus, as their degradation behavior can be precisely controlled by internal or external stimuli to better match the tissue regeneration process. This review systematically summarizes the material types, degradation mechanisms, and biomedical applications of tissue adhesives with on-demand degradation. The adhesives are first classified by source into natural, synthetic, inorganic, and composite types, detailing the characteristics of each category in terms of adhesion, mechanical properties, and degradation behavior. The core mechanisms enabling on-demand degradation are then summarized, including control via responsive chemical bonds, regulation through functional group modification, and manipulation of physical network structure. Finally, the biomedical applications in wound healing and hemostasis, tissue reconstruction, and drug delivery are reviewed, and the challenges and future prospects facing the development of new adhesive systems for regenerative medicine are discussed, aiming to advance the development and clinical translation of tissue adhesives. STATEMENT OF SIGNIFICANCE: This review systematically elaborates on the paradigm shift from passive tissue adhesives to intelligent on-demand degradation systems. Current research predominantly focuses on enhancing adhesive strength while neglecting the precise matching of degradation behavior with the timeline of tissue regeneration-a fundamental limitation hindering their clinical translation. By establishing "on-demand degradation" as a core design principle for the new generation of regenerative medicine materials, this review highlights the critical importance of moving beyond the mere pursuit of strong adhesion towards developing intelligent, degradable systems for preventing long-term complications and achieving seamless integration with the dynamic biological environment. By clarifying the path for this research paradigm transition, our work aims to redefine the core objectives of adhesive design and accelerate the development of solutions with true bio-integrative functions.