Microenvironment-on-chip for chemo-radiotherapy testing

PI - Luca Possenti

This research line aims to contribute to advancing preclinical models by developing innovative microfluidic chips for chemo and radiotherapy applications. Microfluidic chip technologies consist of interconnected channels with a micrometer-scale dimension, replicating key features of the human (tumor) microenvironment and the human vasculature in vitro. By combining biomedical engineering, biological, and computational modelling expertise, these platforms will foster the investigation of chemoradiotherapy efficacy for oncological applications. 

Particularly, we report two main applications related to radiotherapy effects on the human microvasculature and chemo-radiotherapy analyses for pancreatic cancer. 

For the first, we investigated how ionizing radiation and hadron therapy affect healthy tissue, particularly vascular damage, by using a human microvasculature on-chip model replicating a human microvascular network in vitro by three-dimensional culture of endothelial cells.  

The second model focuses on pancreatic ductal adenocarcinoma (PDAC), an aggressive cancer with a dense, fibrotic microenvironment that frequently limits the efficacy of conventional therapies. The primary aim is to build a tumor-on-chip technology to mimic the PDAC microenviroment in vitro to study the effectiveness of chemo and radiotherapy.  

The in vitro studies are complemented by computational simulations to study cellular responses to treatment, offering valuable tools to guide and optimize therapeutic strategies.  

Together, these models provide a biologically relevant platform for improving the prediction of treatment outcomes and accelerating the development of more complex preclinical models.