On‐Demand Chemically Degradable Hydrogels for Biological Applications

Across various wound care applications, device interfaces, drug depots, and cell cultures, materials often require rapid and clean removal. On-demand chemically induced degradable hydrogels fulfill this requirement through small-molecule triggers that cleave covalent crosslinks or disrupt noncovalent interactions. Some of them readily accommodate therapeutic functions such as anti-inflammatory or antioxidant payload delivery while maintaining desired material properties, including self-healing, robust wet adhesion, cytocompatibility, and traceless dissolution. Chemical triggers provide a scalable and rapid dissolution method along with easy removal. In this review, we summarize gelation and degradation mechanisms, commonly used chemical triggers, representative biological applications, and degradation kinetics for both covalent and noncovalent disruption. The advantages and limitations in biocompatible and bioorthogonal approaches are discussed in detail, along with mechanistic development prospects and current clinical challenges for on-demand chemically degradable hydrogels.