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Fabricating Degradable Thermoresponsive Hydrogels on Multiple Length Scales via Reactive Extrusion, Microfluidics, Self-assembly, and Electrospinning

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On-Demand Chemically Degradable Hydrogels for Biological Applications.

Xinyi Sheng¹, Justin Kim¹

¹School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, USA.

Chembiochem : a European Journal of Chemical Biology

|March 23, 2026

Summary

Chemically degradable hydrogels offer rapid, on-demand removal for biomedical applications. These advanced materials enable controlled drug delivery and traceless dissolution, enhancing wound care and cell culture technologies.

Keywords:

biocompatible bioorthogonal chemically induced hydrogel on‐demand degradable

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Area of Science:

Biomaterials Science
Polymer Chemistry
Regenerative Medicine

Background:

Materials in biomedical applications like wound care and cell cultures often need rapid and clean removal.
Current removal methods can be challenging, impacting device interfaces and therapeutic payload delivery.

Purpose of the Study:

To review on-demand chemically induced degradable hydrogels for biomedical applications.
To summarize gelation, degradation mechanisms, chemical triggers, and biological applications.
To discuss biocompatible and bioorthogonal approaches, their prospects, and clinical challenges.

Main Methods:

Review of literature on covalent and noncovalent chemically degradable hydrogels.
Analysis of small-molecule triggers for cleaving crosslinks or disrupting interactions.
Evaluation of material properties, therapeutic functions, and degradation kinetics.

Main Results:

Chemically degradable hydrogels utilize small-molecule triggers for rapid, on-demand dissolution.
These hydrogels support therapeutic functions (e.g., drug delivery) and possess desirable properties (self-healing, adhesion, cytocompatibility).
Both covalent and noncovalent disruption strategies offer distinct advantages and limitations.

Conclusions:

On-demand chemically degradable hydrogels provide a scalable and efficient solution for material removal in biomedicine.
Further development is needed to address biocompatibility, bioorthogonality, and clinical translation challenges.
These hydrogels hold significant promise for advanced wound care, drug depots, and tissue engineering.