Evaluation of mechano-protective effects of Hyaluronic Acid-based biomaterials on Mesenchymal Stromal Cells under imposed shear stress.

Due to their immunomodulatory capacity and regenerative potential, umbilical cord-derived mesenchymal stromal cells (UC-MSCs) are emerging as an advanced therapy medicinal product (ATMP) to treat inflammation and immunodeficiency or to regenerate damaged tissue, as for Crohn’s disease or osteoarthritis. This ATMP could be delivered via systemic infusion or local injection. The scientific community is now investigating the issue of UC-MSC homing and engraftment, namely the difficulty of attaching to the target tissue and remaining in the injection site. In this work, it is proposed to use two different hyaluronic acid-based biomaterials as cell vehicles: the first is characterized by low molecular weight and low viscosity, the second is characterized by the combined use of high and low molecular weight hyaluronic acids. This thesis aims to investigate the mechano-protective effect of these two biomaterials used as carriers for UC-MSCs’ delivery. First, the mechanical stress will be evaluated during the syringe extrusion of biomaterials loaded with cells using Computational Fluid Dynamic (CFD) analysis to determine how cell viability is influenced by shear stress. After that, the in situ protection of the two biomaterials will be evaluated developing two different perfusion bioreactors: the first one will evaluate the protection in two dimensions using a Petri dish with a custom-made PDMS channel to impose a uniform and controlled shear stress; the second one investigate the protection of the two biomaterials in a tridimensional environment using a commercially available porous collagen scaffold continuously perfused with culture medium to mimic the in vivo environment. The results show different protection levels performed by biomaterials, highlighting the importance of mechanically protecting cells to enhance their therapeutic effect.