# On‐Demand Chemically Degradable Hydrogels for Biological Applications

## TL;DR

This review discusses hydrogels that can be rapidly and cleanly removed using chemical triggers for various biological applications.

## Contribution

The paper provides a comprehensive overview of on-demand chemically degradable hydrogels, emphasizing their mechanisms, applications, and clinical potential.

## Key findings

- Chemically triggered hydrogels offer rapid and clean removal with therapeutic functions.
- Covalent and noncovalent degradation mechanisms are compared for biocompatibility and bioorthogonality.
- Degradation kinetics and clinical challenges are analyzed for diverse biological applications.

## Abstract

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.

This review explores the mechanisms and kinetics of chemically induced on‐demand degradation in hydrogels designed for painless dressing removal and traceless dissolution across various biological applications. Covalent bond cleavage and noncovalent disruption triggers are compared, highlighting opportunities for load‐bearing scaffolds with faster trigger response, strong biocompatibility, high bioorthogonality, minimal invasiveness, broad accessibility, and tunable degradability to meet diverse clinical needs.© 2026 WILEY‐VCH GmbH