3D Bioprinting of Functional Islets of Langerhans in an Alginate/Methylcellulose Hydrogel Blend

Adv Healthc Mater. 2019 Apr;8(7):e1801631. doi: 10.1002/adhm.201801631. Epub 2019 Mar 5.

Abstract

Transplantation of pancreatic islets is a promising strategy to alleviate the unstable blood-glucose control that some patients with diabetes type 1 exhibit and has seen many advances over the years. Protection of transplanted islets from the immune system can be accomplished by encapsulation within a hydrogel, the most investigated of which is alginate. In this study, islet encapsulation is combined with 3D extrusion bioprinting, an additive manufacturing method which enables the fabrication of 3D structures with a precise geometry to produce macroporous hydrogel constructs with embedded islets. Using a plottable hydrogel blend consisting of clinically approved ultrapure alginate and methylcellulose (Alg/MC) enables encapsulating pancreatic islets in macroporous 3D hydrogel constructs of defined geometry while retaining their viability, morphology, and functionality. Diffusion of glucose and insulin in the Alg/MC hydrogel is comparable to diffusion in plain alginate; the embedded islets continuously produce insulin and glucagon throughout the observation and still react to glucose stimulation albeit to a lesser degree than control islets.

Keywords: 3D bioprinting; alginate; diabetes; insulin; macroporous; pancreatic islet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry
  • Animals
  • Bioprinting / methods*
  • Cell Survival / drug effects
  • Female
  • Glucose / metabolism
  • Hydrogels / chemistry*
  • Hydrogels / pharmacology
  • Insulin / metabolism
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans Transplantation
  • Methylcellulose / chemistry
  • Porosity
  • Printing, Three-Dimensional*
  • Rats
  • Rats, Wistar
  • Tissue Engineering
  • Tissue Scaffolds / chemistry

Substances

  • Alginates
  • Hydrogels
  • Insulin
  • Methylcellulose
  • Glucose