Organ Models

Project objectives

The MIND project aims to address the current lack of a model for studying the physiological conditions associated with aging by developing, using advanced bioengineering technologies, dynamic in vitro models capable of reproducing the physiopathological conditions of aging tissue, while adhering to the 3Rs principle ("Replacement, Refinement, Reduction") of animal testing. The multidisciplinary nature of the consortium, composed primarily of bioengineers, supported by clinicians, biologists, healthcare regulatory experts, physicists, and electronic engineers, allows for the integration of knowledge to design, model, build, and characterize new systems for the in vitro study of aging and age-related degradation processes, with particular reference to four tissue types: cardiac, bone, epithelial, and neural. Specifically, biomimetic scaffolds are designed to reproduce the morphological, biochemical, and mechanical characteristics of the cardiac and bone extracellular matrix at two different levels of aging (young and aged tissue). These scaffolds are populated with cardiac and bone cells, respectively, and cultured in specially designed tissue-specific bioreactors. To create an in vitro model of brain aging, cortical neuronal networks are coupled to standard and high-density microelectrode arrays or, alternatively, organic field-effect transistors for electrophysiology and metabolic activity recording. The systems are integrated into membrane bioreactors to model the blood-brain barrier coupled with a central nervous system model. The dynamic epithelial barrier model uses semipermeable membranes actuated to simulate peristaltic movement. Intestinal epithelial cells are seeded onto membranes made of dielectric elastomeric actuators, after optimizing their biocompatibility, integrating electrodes with specific geometries, and applying specific voltage profiles to vary their compliance and induce rhythmic movements. Furthermore, bioreactors with dedicated chambers to house the membranes are designed and developed. Experiments are guided by appropriate in silico gene-metabolic cellular models, computational fluid dynamics models, and mechanical models. The model tissues developed in the project are characterized through histological and mechanical analysis, and possibly electrophysiological measurements, and appropriately validated. They allow us to assess the susceptibility of senescent tissues to oxidative damage, hypoxic conditions, the presence of pro-inflammatory cytokines, and nanoparticles.

Start and end date

February 2013 - February 2015

Project Manager

Prof. Massimo Chello – Extraordinary Professor

Coordinating institution of the project

Polytechnic University of Turin - Department of Mechanical and Aerospace Engineering

Other Institutions involved

• Università Campus Bio-Medico di Roma - INTEGRATED RESEARCH CENTER (CIR)

• University of Turin - Department of Genetics, Biology, and Biochemistry

• National Research Council Institute of Clinical Physiology

• Polytechnic University of Milan - Department of Structural Engineering

• University of Calabria - Department of Chemical and Materials Engineering

• University of Cagliari - Department of Electrical and Electronic Engineering

• University of Bologna - Department of Physics

• Polytechnic University of Marche - Department of Clinical and Molecular Sciences  

Funding source(s).

PRIN: project funded under Call No. 12/Ric/2012