Voxelated bioprinting of modular double-network bio-ink droplets

Nat Commun. 2024 Jul 13;15(1):5902. doi: 10.1038/s41467-024-49705-z.

Abstract

Analogous of pixels to two-dimensional pictures, voxels-in the form of either small cubes or spheres-are the basic building blocks of three-dimensional objects. However, precise manipulation of viscoelastic bio-ink voxels in three-dimensional space represents a grand challenge in both soft matter science and biomanufacturing. Here, we present a voxelated bioprinting technology that enables the digital assembly of interpenetrating double-network hydrogel droplets made of polyacrylamide/alginate-based or hyaluronic acid/alginate-based polymers. The hydrogels are crosslinked via additive-free and biofriendly click reaction between a pair of stoichiometrically matched polymers carrying norbornene and tetrazine groups, respectively. We develop theoretical frameworks to describe the crosslinking kinetics and stiffness of the hydrogels, and construct a diagram-of-state to delineate their mechanical properties. Multi-channel print nozzles are developed to allow on-demand mixing of highly viscoelastic bio-inks without significantly impairing cell viability. Further, we showcase the distinctive capability of voxelated bioprinting by creating highly complex three-dimensional structures such as a hollow sphere composed of interconnected yet distinguishable hydrogel particles. Finally, we validate the cytocompatibility and in vivo stability of the printed double-network scaffolds through cell encapsulation and animal transplantation.

MeSH terms

  • Acrylic Resins* / chemistry
  • Alginates* / chemistry
  • Animals
  • Biocompatible Materials / chemistry
  • Bioprinting* / methods
  • Cell Survival
  • Humans
  • Hyaluronic Acid* / chemistry
  • Hydrogels* / chemistry
  • Ink
  • Mice
  • Printing, Three-Dimensional
  • Tissue Engineering / methods

Substances

  • Hydrogels
  • Alginates
  • Hyaluronic Acid
  • Acrylic Resins
  • polyacrylamide
  • Biocompatible Materials