Multi-casting approach for vascular networks in cellularized hydrogels

J R Soc Interface. 2016 Dec;13(125):20160768. doi: 10.1098/rsif.2016.0768.

Abstract

Vascularization is essential for living tissue and remains a major challenge in the field of tissue engineering. A lack of a perfusable channel network within a large and densely populated tissue engineered construct leads to necrotic core formation, preventing fabrication of functional tissues and organs. We report a new method for producing a hierarchical, three-dimensional (3D) and perfusable vasculature in a large, cellularized fibrin hydrogel. Bifurcating channels, varying in size from 1 mm to 200-250 µm, are formed using a novel process in which we convert a 3D printed thermoplastic material into a gelatin network template, by way of an intermediate alginate hydrogel. This enables a CAD-based model design, which is highly customizable, reproducible, and which can yield highly complex architectures, to be made into a removable material, which can be used in cellular environments. Our approach yields constructs with a uniform and high density of cells in the bulk, made from bioactive collagen and fibrin hydrogels. Using standard cell staining and immuno-histochemistry techniques, we showed good cell seeding and the presence of tight junctions between channel endothelial cells, and high cell viability and cell spreading in the bulk hydrogel.

Keywords: hydrogel; three-dimensional printing; vascular networks; vascularization.

MeSH terms

  • Alginates / chemistry*
  • Cell Survival
  • Gelatin / chemistry*
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Hydrogels / chemistry*
  • Tissue Scaffolds / chemistry*

Substances

  • Alginates
  • Hexuronic Acids
  • Hydrogels
  • Glucuronic Acid
  • Gelatin