Design and development of a dual-flow bioreactor mimicking intestinal peristalsis and permeability in epithelial tissue barriers for drug transport assessment

Odin Ram蚏Ez-Fern罭Dez,Joana Costa,Benjam韓 Leon-Mancilla,Ludovika Cacopardo

doi:10.32604/biocell.2019.04790

Abstract

we present a bioreactor system which combines a semi permeable membrane that simulates the osmotic nutrients interchange in the intestine circulation and rhythmic peristaltic movement. This custom-designed, pulsatile membrane bioreactor, with programmable manipulation, allows adjustment of luminal flow rate. In addition, this system is also capable of achieving the intestine-like drug distribution to the cells by the luminal perfusion of the hollow channel compartment. This dynamic platform can mimic the human intestine with increased accuracy to overcome many of the limitations with the previously described in vitro intestinal models, providing a more representative model of the human intestine.

Highlights

The major site for digestion, drug and nutrient absorption is the small intestine, the interaction with commensal microbiome, and development of mucosal immunity because is the primary site for many diseases, such as bacterial, viral and parasitic infections and inflammatory bowel disease (Turner, 2009).Bioreactor models are replicates of the structure and biomechanical function of biological tissues that allow mimicking and predicting physiological responses to a variety of stimuli (Peterson and Artis, 2014)
Animal models allow the development of novel therapies for intestinal diseases, but they are costly and often do not reflect the corresponding human disease, and many new drugs that have successfully passed animal trials fail during the human clinical trial phase (Marx, 2015; Barbara et al, 2016; Gayer and Basson, 2009)
In the frontal view, where a suction vortex can be appreciated at the bioreactor exit, there is no possibility for static zones inside the apical chamber and it assures the successful flow exchange

Summary

Introduction

The major site for digestion, drug and nutrient absorption is the small intestine, the interaction with commensal microbiome, and development of mucosal immunity because is the primary site for many diseases, such as bacterial, viral and parasitic infections and inflammatory bowel disease (Turner, 2009).Bioreactor models are replicates of the structure and biomechanical function of biological tissues that allow mimicking and predicting physiological responses to a variety of stimuli (Peterson and Artis, 2014). Traditional static models and conventional substrates for cell culture, like plastic flasks, dishes, plates, wells or cover slips, offer ease of use and have low cost, they are not fully representative of the biological responses, as they do not mimic key aspects of the biomechanical environment. Animal models allow the development of novel therapies for intestinal diseases, but they are costly and often do not reflect the corresponding human disease, and many new drugs that have successfully passed animal trials fail during the human clinical trial phase (Marx, 2015; Barbara et al, 2016; Gayer and Basson, 2009). The bioreactors offer an alternative to animal models for quantitative studies and tests of new drugs and their permeation in a verifiable, cost-efficient manner, through a biologically driven approach in vitro (Rigottier-Gois, 2013)

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