Programmable tissue-adhesive hydrogels with temporal and spatial selectivity

With the expanding application of hydrogels in the biomedical filed, tissue-adhesive hydrogels (TAHs) have emerged as a critical focus of research. Unlike conventional adhesives, achieving effective tissue adhesion requires a sophisticated strategy that addresses the challenges posed by the complex biological microenvironment. Critical considerations in hydrogel design include the dynamic wet environment in vivo, spatiotemporally controlled adhesion, and asymmetric interfacial interactions. These properties cannot be attained through universal solutions but require customized design frameworks integrating multi-scale engineering principles. Recent advances have systematically optimized hydrogel adhesion through integrating multi-scale design principles: microscale mechanisms of physical/chemical interactions, molecular-scale modifications such as hydrophobic chain segments and topological entanglements, and macroscale structural patterning. Driven by advancements in polymer science, materials science, and biomedical engineering, the development of TAHs has evolved from single-function adhesion enhancement to the rational design of multifunctional bioactive adhesive systems with programmable adhesion across multiple dimensions. This review provides a comprehensive overview of current advancements in TAHs, identifies key challenges in clinical translation, and proposes future directions to bridge fundamental discoveries with practical biomedical applications.