Modular plug-and-play crosslinking platform for precision-engineered hydrogels

Evans, Austin D., Parvathaneni, Rohith P., Rahikainen, Rolle, Varghese, Oommen P., Hytönen, Vesa P. and Oommen, Oommen P. ORCID: https://orcid.org/0000-0003-2768-0133 2026. Modular plug-and-play crosslinking platform for precision-engineered hydrogels. Cell Reports Physical Science 7 (8) , 103457. 10.1016/j.xcrp.2026.103457

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Abstract

Hydrogels are promising for biomedical applications due to their tunable properties and extracellular matrix (ECM)-mimicking capabilities, but available chemistries limit customization potential. We present a modular bioconjugation system using polyphenol radical crosslinking, where gallic acid (GA)-modified glycosaminoglycans rapidly crosslink with diverse biomolecules under blue light and riboflavin. This method enables the creation of customizable, cell-compatible matrices. We validate conjugation chemistry using 1H NMR, size-exclusion chromatography, and gel electrophoresis. As proof-of-concept, we have created injectable hydrogels from GA-modified hyaluronic acid (HA-GA) crosslinked with various proteins. Mechanical properties are tunable via riboflavin concentration and light exposure. HCT116 colon cancer cells form spheroids in HA-GA-BSA, while other protein-containing hydrogels support dispersed growth, indicating enhanced cell adhesion. HA-GA hydrogels upregulate stemness markers compared to 2D culture, while protein incorporation reduces this effect. Matrix-activated Wnt signaling confirms functional biomolecule integration using HA-GA-Wnt3A matrices. This strategy enables tailored ECM design for tissue engineering and 3D cell culture.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Pharmacy
Publisher:	Elsevier
ISSN:	2666-3864
Date of First Compliant Deposit:	5 August 2026
Date of Acceptance:	6 July 2026
Last Modified:	05 Aug 2026 08:30
URI:	https://orca.cardiff.ac.uk/id/eprint/188735

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