Sibilio, Sara (2021) Developing of an organ on chip device as novel in vitro platform to study organ mechanobiology: Peristalsis on a chip. [Tesi di dottorato]

Preview

Text Sibilio_Sara_33.pdf Download (23MB) | Preview

Collection description

Developing of an organ on chip device as novel in vitro platform to study organ mechanobiology: Peristalsis on a chip. Knowing the mechanical properties of the gastrointestinal (GI) tract appears to be important for understanding the molecular and cellular responses to mechanical stimuli on physiological processes such as foods, xenobiotic or drugs digestion/absorption. These processes are mediated by various intestinal cells such as epithelial cells, interstitial cells, smooth muscle cells, and neurocytes. The loss or dysfunction of specific cells or mechanical strength of cell bowel wall directly results in GI tract disease. Reversing the abnormal status of pathogenic cells has been considered crucial to treatment of gut diseases. Gut bioengineered models have been developing for the purpose to replace the damaged tissues and to provide three-dimensional platforms that mimic the in vivo environment to study drug development, absorption and toxicity. Nevertheless, the need to develop more complex models in vitro to study mechanical stress is growing. In this perspective, this project will allow us to get an automatized microfluidic gut platform to evaluate the pathophysiology of the small intestine through the study of the shear stress of the bolus on the epithelial cells layer at the lumen side of the healthy or diseased 3D intestine models. To this aim, the major goals of this project are the the design and fabrication of complex and innovative microfluidic device provided with an integrated PDMS membrane designed to mimic the crypt-villus axis in order to promote the differentiation of the intestinal epithelium and the establishment of peristaltic motion by means of an automatized and controlled elettrovalve system. The platform was used to estimate the intestinal transport properties of the bolus and the physiological condition of the shear stress under peristaltic motion. An important feature of the device, is the possibility to induce a fluid flow both at the basolateral and the lumen side of the intestinal epithelium, therefore the possibility to introduce integrated electrodes in the apical side and basoteral side in order to be enable continuous monitoring of cells behaviour and differentiation through TransEpithelial Electrical Resistance measurements. The effect of PDMS membrane morphology, peristaltic motion and shear stress on intestinal epithelial cell differentiation, mucus production and molecules adsorption process has been evaluated. The development of the Peristalsis on chip device could be reduce the poorly predictive preclinical evaluation generated by the phylogenetic distance between laboratory animals and humans, the discrepancy between current in vitro systems and the human body, and the restrictions of in silico modelling.

Downloads

Actions (login required)

View Item