Injectable Hydrogels Based on Inter-Polyelectrolyte Interactions between Hyaluronic Acid, Gelatin, and Cationic Cellulose Nanocrystals

Christine Warwar Damouny, Patrick Martin, Gleb Vasilyev, Rita Vilensky, Reema Fadul, Idan Redenski, Samer Srouji, Eyal Zussman

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


The present work dealt with the development of physically cross-linked injectable hydrogels with potential applications in tissue engineering. The hydrogels were composed of a ternary mixture of a polyanion and a polyampholyte, hyaluronic acid (HA) and gelatin, respectively, bridged by cationic cellulose nanocrystals (cCNCs). A 3D network is formed by employing attractive electrostatic interactions and hydrogen bonding between these components under physiological conditions. The hydrogels demonstrated low viscosity at high stresses, enabling easy injection, structural stability at low stresses (<15 Pa), and nearly complete structure recovery within several minutes. Increasing the cCNC content (>3%) reduced hydrogel swelling and decelerated the degradation in phosphate-buffered saline as compared to that in pure HA and HA-gelatin samples. Biological evaluation of the hydrogel elutions showed excellent cell viability. The proliferation of fibroblasts exposed to elutions of hydrogels with 5% cCNCs reached ∼200% compared to that in the positive control after 11 days. Considering these results, the prepared hydrogels hold great potential in biomedical applications, such as injectable dermal fillers, 3D bioprintable inks, or 3D scaffolds to support and promote soft tissue regeneration.

Original languageEnglish
Pages (from-to)3222-3234
Number of pages13
Issue number8
StatePublished - 8 Aug 2022

Bibliographical note

Publisher Copyright:
© 2022 American Chemical Society.


This work was supported by the Russell Berrie Nanotechnology Institute (RBNI). E.Z. acknowledges the financial support of the Winograd Chair of Fluid Mechanics and Heat Transfer at Technion.

FundersFunder number
Russell Berrie Nanotechnology Institute
Technion-Israel Institute of Technology


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