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Related Experiment Video

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Engineering a Hydrazone and Triazole Crosslinked Hydrogel for Extrusion-Based Printing and Cell Delivery.

Matthew W Jaeschke1,2, Alexandra N Borelli1,2, Nathaniel P Skillin1,2,3

  • 1Department of Chemical and Biological Engineering, Boulder, CO, 80303, USA.

Advanced Healthcare Materials
|May 28, 2024
PubMed
Summary

This study enhances hyaluronic acid hydrogels for bioink applications by incorporating stable triazole bonds, improving injectability and cell viability for advanced 3D bioprinting.

Keywords:
covalent adaptable networksextrusion‐based printinghydrazoneinjectable hydrogelsmesenchymal stem cell

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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Tissue Engineering

Background:

  • Alkyl-hydrazone crosslinks offer tunable viscoelasticity for hydrogels but lack stability in biological settings.
  • Hyaluronic acid (HA) hydrogels with low molecular weight or content are limited by poor injectability.
  • Existing hydrogel systems require modification for improved stability and printability in cell delivery applications.

Purpose of the Study:

  • To enhance the stability and injectability of hyaluronic acid-based hydrogels for extrusion-based bioprinting.
  • To investigate the role of triazole bonds formed via strain-promoted azide-alkyne cycloaddition (SPAAC) in hydrogel properties.
  • To optimize hydrogel formulations for improved cell viability and function in bioink applications.

Main Methods:

  • Modification of high molecular weight HA with azide groups.
  • Formation of triazole crosslinks using SPAAC reaction with bicyclononyne-functionalized PEG.
  • Incorporation of methyl-PEG4-hydrazide to modulate network evolution and extrusion properties.

Main Results:

  • Increasing SPAAC crosslinking (0-12%) significantly enhanced hydrogel stability.
  • SPAAC hydrogels exhibited transient self-healing and comparable extrusion force to non-SPAAC hydrogels.
  • Addition of methyl-PEG4-hydrazide improved printability, lowered extrusion force, and increased cell viability and function.

Conclusions:

  • High molecular weight HA-PEG hydrogels with SPAAC crosslinking demonstrate improved stability and tunable injectability.
  • The developed hydrogels are suitable for extrusion-based 3D bioprinting and cell delivery.
  • This approach offers a promising strategy for creating advanced biomaterials for regenerative medicine.