Three-dimensional extrusion bioprinting of single- and double-network hydrogels containing dynamic covalent crosslinks

J Biomed Mater Res A. 2018 Apr;106(4):865-875. doi: 10.1002/jbm.a.36323. Epub 2018 Jan 23.

Abstract

The fabrication of three-dimensional (3D) scaffolds is indispensable to tissue engineering and 3D printing is emerging as an important approach towards this. Hydrogels are often used as inks in extrusion-based 3D printing, including with encapsulated cells; however, numerous challenging requirements exist, including appropriate viscosity, the ability to stabilize after extrusion, and cytocompatibility. Here, we present a shear-thinning and self-healing hydrogel crosslinked through dynamic covalent chemistry for 3D bioprinting. Specifically, hyaluronic acid was modified with either hydrazide or aldehyde groups and mixed to form hydrogels containing a dynamic hydrazone bond. Due to their shear-thinning and self-healing properties, the hydrogels could be extruded for 3D printing of structures with high shape fidelity, stability to relaxation, and cytocompatibility with encapsulated fibroblasts (>80% viability). Forces for extrusion and filament sizes were dependent on parameters such as material concentration and needle gauge. To increase scaffold functionality, a second photocrosslinkable interpenetrating network was included that was used for orthogonal photostiffening and photopatterning through a thiol-ene reaction. Photostiffening increased the scaffold's modulus (∼300%) while significantly decreasing erosion (∼70%), whereas photopatterning allowed for spatial modification of scaffolds with dyes. Overall, this work introduces a simple approach to both fabricate and modify 3D printed scaffolds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 865-875, 2018.

Keywords: 3D printing; dynamic covalent chemistry; hydrazone; hydrogel; injectable.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bioprinting*
  • Cell Survival
  • Cross-Linking Reagents / chemistry*
  • Hyaluronic Acid / chemistry
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry
  • Injections
  • Mechanical Phenomena
  • Mice
  • NIH 3T3 Cells
  • Printing, Three-Dimensional*

Substances

  • Cross-Linking Reagents
  • Hydrogels
  • Hyaluronic Acid