Linking Polysaccharide Structure, Gelation Kinetics, and Function in Dynamic Acylhydrazone Hydrogels
- 1Polymer Institute of the Slovak Academy of Sciences, Dubravska cesta 9, 845 41, Bratislava, Slovakia; Advanced Biomaterials, Central European Institute of Techn
Abstract
Dynamic covalent hydrogels formed through reversible acylhydrazone crosslinking have emerged as promising injectable biomaterials. However, a fundamental gap remains in understanding how the macromolecular structure of oxidized polysaccharides (OxPs) governs gelation kinetics and how these kinetics pathways translate into material properties and cellular responses. We address this question by developing an acylhydrazone hydrogel library composed of alginate adipohydrazide crosslinked with oxidized alginate (OxA) or oxidized dextran (OxD), two reactive aldehyde-bearing polymers with comparable chemical functionality but fundamentally distinct backbone structure. By varying polysaccharide type, oxidation degree, and reaction pH, we decoupled the effects of chemical functionality from macromolecular structure and established quantitative structure-kinetics-property-function relationships. OxD-based hydrogels undergo rapid, largely pH-independent gelation, whereas OxA-based systems display pronounced pH-dependent kinetics with significantly delayed network formation under physiological pH. These differences in gelation kinetics and OxPs macromolecular structures lead to marked variations in hydrogel mechanics, including stiffness, stress relaxation, stability, injectability, and post-injection recovery. Importantly, differences in gelation kinetics modulate cell-matrix interactions in three-dimensional culture. Slowly forming OxA hydrogels maintained rounded chondrocyte shape, while rapidly gelling OxD networks induced transient cell elongation. Mesenchymal stem cells displayed similar shapes regardless of gelation kinetics, indicating cell-type-specific responses to matrix formation dynamics.
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BibTeX
@misc{kazemiaghdam2026linking,
title = {{Linking Polysaccharide Structure, Gelation Kinetics, and Function in Dynamic Acylhydrazone Hydrogels}},
author = {F. Kazemi-Aghdam and Z. Varchulova and J. Zvicer and J. Stojkovska and A. Krizov and S. Dinparvar and L. Vojtova and L. Danisovic and I. Lacik and A. Heydari},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.752777},
url = {https://www.biorxiv.org/content/10.64898/2026.09.25.752777v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Linking Polysaccharide Structure, Gelation Kinetics, and Function in Dynamic Acylhydrazone Hydrogels
AU - F. Kazemi-Aghdam
AU - Z. Varchulova
AU - J. Zvicer
AU - J. Stojkovska
AU - A. Krizov
AU - S. Dinparvar
AU - L. Vojtova
AU - L. Danisovic
AU - I. Lacik
AU - A. Heydari
PY - 2026
DA - 2026/09/25
PB - bioRxiv
DO - 10.64898/2026.09.25.752777
UR - https://www.biorxiv.org/content/10.64898/2026.09.25.752777v1
AB - Dynamic covalent hydrogels formed through reversible acylhydrazone crosslinking have emerged as promising injectable biomaterials. However, a fundamental gap remains in understanding how the macromolecular structure of oxidized polysaccharides (OxPs) governs gelation kinetics and how these kinetics pathways translate into material properties and cellular responses. We address this question by developing an acylhydrazone hydrogel library composed of alginate adipohydrazide crosslinked with oxidized alginate (OxA) or oxidized dextran (OxD), two reactive aldehyde-bearing polymers with comparable chemical functionality but fundamentally distinct backbone structure. By varying polysaccharide type, oxidation degree, and reaction pH, we decoupled the effects of chemical functionality from macromolecular structure and established quantitative structure-kinetics-property-function relationships. OxD-based hydrogels undergo rapid, largely pH-independent gelation, whereas OxA-based systems display pronounced pH-dependent kinetics with significantly delayed network formation under physiological pH. These differences in gelation kinetics and OxPs macromolecular structures lead to marked variations in hydrogel mechanics, including stiffness, stress relaxation, stability, injectability, and post-injection recovery. Importantly, differences in gelation kinetics modulate cell-matrix interactions in three-dimensional culture. Slowly forming OxA hydrogels maintained rounded chondrocyte shape, while rapidly gelling OxD networks induced transient cell elongation. Mesenchymal stem cells displayed similar shapes regardless of gelation kinetics, indicating cell-type-specific responses to matrix formation dynamics.
ER -