Nucleoside-Based Cross-Linkers for Hydrogels with Tunable Properties

Rafael Itzhakov, Dmitry Tworowski, Noy Sadot, Tali Sayas, Elazar Fallik, Maya Kleiman, Elena Poverenov

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Herein, we report bioderived cross-linkers to create biopolymer-based hydrogels with tunable properties. Nucleosides (inosine and uridine) and ribose (pentose sugar lucking the nitrogenous base) were partially oxidized to yield inosine dialdehyde (IdA), uridine dialdehyde (UdA), and ribose dialdehyde (RdA). The dialdehydes were further used as cross-linkers with polysaccharide chitosan to form hydrogels. Depending on the cross-linker type and concentration, the hydrogels showed tunable rheological, mechanical, and liquid holding properties allowing the preparation of injectable, soft, and moldable hydrogels. Computational modeling and molecular dynamics simulations shed light on hydrogel formation and revealed that, in addition to covalent bonding, noncovalent interactions (π-π stacking, cation−π, and H-bonding) also significantly contributed to the cross-linking process. To demonstrate various application possibilities, the prepared hydrogels were used as a growth platform for plant cells, as injectable inks for layer-by-layer 3D printing applications, and as moldable hydrogels for soft lithography to replicate the microstructure of the plant. These findings suggest that the obtained tunable biocompatible hydrogels have the potential to be good candidates for various biotechnological applications.

Original languageEnglish
Pages (from-to)7359-7370
Number of pages12
JournalACS applied materials & interfaces
Issue number5
StatePublished - 8 Feb 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society.


The authors thank Dr. Erez Cohen and Dr. Sai Sateesh Sagiri for scientific discussions. This research was partially supported by the Israel Science Foundation (ISF), grant agreement no. 2036/21.

FundersFunder number
Israel Science Foundation2036/21


    • biocompatibility
    • biopolymers
    • chitosan
    • cross-linkers
    • hydrogels
    • nucleosides


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