A new microfluidic method enabling the generation of multi-layered tissues-on-chips using skin cells as a proof of concept

Sci Rep. 2021 Jun 23;11(1):13160. doi: 10.1038/s41598-021-91875-z.

Abstract

Microfluidic-based tissues-on-chips (TOCs) have thus far been restricted to modelling simple epithelia as a single cell layer, but likely due to technical difficulties, no TOCs have been reported to include both an epithelial and a stromal component despite the biological importance of the stroma for the structure and function of human tissues. We present, for the first time, a novel approach to generate 3D multilayer tissue models in microfluidic platforms. As a proof of concept, we modelled skin, including a dermal and an epidermal compartment. To accomplish this, we developed a parallel flow method enabling the deposition of bilayer tissue in the upper chamber, which was subsequently maintained under dynamic nutrient flow conditions through the lower chamber, mimicking the function of a blood vessel. We also designed and built an inexpensive, easy-to-implement, versatile, and robust vinyl-based device that overcomes some of the drawbacks present in PDMS-based chips. Preliminary tests indicate that this biochip will allow the development and maintenance of multilayer tissues, which opens the possibility of better modelling of the complex cell-cell and cell-matrix interactions that exist in and between the epithelium and mesenchyme, allowing for better-grounded tissue modelling and drug screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Culture Media
  • Equipment Design
  • Fibrin
  • Fibroblasts / cytology*
  • Humans
  • Hydrogels
  • Keratinocytes / cytology*
  • Lab-On-A-Chip Devices*
  • Microfluidic Analytical Techniques / instrumentation*
  • Microfluidics / instrumentation
  • Microfluidics / methods*
  • Microscopy, Fluorescence
  • Proof of Concept Study
  • Rheology
  • Skin / cytology*
  • Time-Lapse Imaging

Substances

  • Culture Media
  • Hydrogels
  • Fibrin