In situ patterned micro 3D liver constructs for parallel toxicology testing in a fluidic device

Biofabrication. 2015 Sep 10;7(3):031001. doi: 10.1088/1758-5090/7/3/031001.

Abstract

3D tissue models are increasingly being implemented for drug and toxicology testing. However, the creation of tissue-engineered constructs for this purpose often relies on complex biofabrication techniques that are time consuming, expensive, and difficult to scale up. Here, we describe a strategy for realizing multiple tissue constructs in a parallel microfluidic platform using an approach that is simple and can be easily scaled for high-throughput formats. Liver cells mixed with a UV-crosslinkable hydrogel solution are introduced into parallel channels of a sealed microfluidic device and photopatterned to produce stable tissue constructs in situ. The remaining uncrosslinked material is washed away, leaving the structures in place. By using a hydrogel that specifically mimics the properties of the natural extracellular matrix, we closely emulate native tissue, resulting in constructs that remain stable and functional in the device during a 7-day culture time course under recirculating media flow. As proof of principle for toxicology analysis, we expose the constructs to ethyl alcohol (0-500 mM) and show that the cell viability and the secretion of urea and albumin decrease with increasing alcohol exposure, while markers for cell damage increase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival
  • Equipment Design
  • Ethanol
  • Hep G2 Cells
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Liver / cytology*
  • Microfluidic Analytical Techniques / instrumentation*
  • Models, Biological*
  • Tissue Array Analysis / instrumentation*
  • Tissue Engineering / instrumentation
  • Tissue Engineering / methods*
  • Toxicity Tests / instrumentation*

Substances

  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Ethanol