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.
Highlights
Microfluidic-based tissues-on-chips (TOCs) have 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
TOCs represent an important leap towards the generation of improved in vitro epithelial models, challenges such as downscaling preserving tissue function or the lack of a biologically meaningful stromal component still await s olution[23]
Since many tumours are of epithelial origin, it is of great importance to work up epithelia with a stromal component to take into consideration the well-known role of the microenvironment in tumorigenesis
Summary
Microfluidic-based tissues-on-chips (TOCs) have 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. Recent interest has focused on generating in vitro 3D tissue models, such as skin and gut, in cell culture insert (CCI) formats with dynamic perfusion These platforms enable a more physiological transport of nutrients, permitting a more reliable evaluation of drug candidates in terms of toxicity, efficacy and d elivery[15,16,17,18,19]. Given the importance of having bioengineered skin for its clinical applications, in the field of wound healing, in the testing of cosmetics and drugs, and in contributing to the long-lasting interest in achieving an effective transdermal application of drugs, these dynamic CCI cultures have been used to model complex 3D dermo-epidermal equivalents They have incorporated vascularization, cyclic stress, immune cells or more than a tissue. For a recent review, see[46]
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