Hydrogel with high-order structures: from hierarchical engineering to flexible biomedical applications

Hydrogels are promising for flexible biomedical systems, yet their performance is often constrained by conventional composition-dominated networks, which are typically randomly crosslinked and structurally homogeneous, and therefore lack efficient pathways for stress transfer, transport regulation, and integrated functional responses. This challenge has motivated increasing interest in introducing structural order as a key design principle, particularly through supramolecular interactions and other assembly-driven strategies. In this review, we focus on hydrogels with high-order structures, in which deliberately engineered organization serves as a key determinant of material properties and biological functions. We first distinguish these systems from conventional strategies and propose an architectural framework to describe how organization across molecular, nanoscale, mesoscale, and network levels regulate mechanical properties, molecular transport, and electromechanical behavior. We then summarize the main structural routes for constructing these hydrogels, including phase separation, molecular self-assembly, nanocomposite integration, and crystalline ordering. Building on this framework, we further discuss how structural order governs hydrogel performance across different length scales, with emphasis on structure-function relationships in mechanical reinforcement, signal transduction, and biomedical activity. Particular attention is given to the coupling of multiple structural mechanisms, especially the integration of dynamic interactions with phase-separated, nanocomposite, or crystalline domains, as an effective strategy for achieving multifunctionality and adaptive performance. Finally, we outline current challenges in predictive structural design, dynamic stability, and scalable fabrication, and highlight future prospects for hydrogels with improved structural precision and biomedical relevance.