Dual‐chambered membrane bioreactor for coculture of stratified cell populations

Abstract

We have developed a dual-chambered bioreactor (DCB) that incorporates a membrane to study stratified 3D cell populations for skin tissue engineering. The DCB provides adjacent flow lines within a common chamber; the inclusion of the membrane regulates flow layering or mixing, which can be exploited to produce layers or gradients of cell populations in the scaffolds. Computational modeling and experimental assays were used to study the transport phenomena within the bioreactor. Molecular transport across the membrane was defined by a balance of convection and diffusion; the symmetry of the system was proven by its bulk convection stability, while the movement of molecules from one flow line to the other is governed by coupled convection-diffusion. This balance allowed the perfusion of two different fluids, with the membrane defining the mixing degree between the two.The bioreactor sustained two adjacent cell populations for 28 days, and was used to induce indirect adipogenic differentiation of mesenchymal stem cells due to molecular cross-talk between the populations. We successfully developed a platform that can study the dermis-hypodermis complex to address limitations in skin tissue engineering. Furthermore, the DCB can be used for other multilayered tissues or the study of communication pathways between cell populations.

Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration

“…DCB provides adjacent flow lines within the chamber and the included membrane regulates stratification and flow mixing. This system can be exploited to produce cell population layers or gradients in scaffolds [ 125 ].…”

Novel dual-flow perfusion bioreactor for in vitro pre-screening of nanoparticles delivery: design, characterization and testing

“…An interesting result came out from permeability tests which revealed the possibility to manage the direction of the radial flow simply by changing the height of the outlet of the IPC tube. Consequently, according to the desired application, one can precisely set the direction of the radial flow rate, without the use of specific devices [61] or the more approximating results of a computational simulation [62,63]. Recently, Tan et al presented a new calibration method for the permeability measuring set-ups by testing the outwards radial flow through two concentric annular slits [64].…”

Surface Engineering of a Bioartificial Membrane for Its Application in Bioengineering Devices

“…Dual-chambered bioreactors developed by Javier Navarro et al allowed for better transport mechanisms owing to the dual action of convection and diffusion patterns. Two different cell populations were developed on the two sides of the membrane and successfully paved the way for the development of skin tissue in vitro, which consists of multiple morphologically distinct layers of cells of a similar lineage . This approach might also be helpful in the development of interface tissue engineering.…”