Double Flow Bioreactor for In Vitro Test of Drug Delivery

Abstract

In this work, double-structured polymeric scaffolds were produced, and a double flow bioreactor was designed and set up in order to create a novel system to carry out advanced in vitro drug delivery tests. The scaffolds, consisting of a cylindrical porous matrix, are able to host cells, thus mimicking a three-dimensional tumor mass: moreover, a "pseudo-vascular" structure was embedded into the matrix, with the aim of allowing a flow circulation. The structure that emulates a blood vessel is a porous tubular-shaped scaffold prepared by Diffusion Induced Phase Separation (DIPS), with an internal lumen of 2 mm and a wall thickness of 200 micrometers. The as-prepared vessel was incorporated into a three-dimensional matrix, prepared by Thermally Induced Phase Separation (TIPS), characterized by a high porosity (about 95%) and pore size adequate to accommodate tumor cells and/or mesenchymal cells. The morphology of the multifunctional scaffolds is easy-tunable in terms of pore size, porosity and thickness and therefore adaptable to various cell or tissue types. At the same time, a double flow bioreactor was designed and built up, in order to be able to carry out biological tests on the scaffold under dynamic conditions. The device allows a separate control of the two flows (one for the tubular scaffold, one for the porous matrix) through the scaffolds. Preliminary characterizations and tests carried out suggest the presented system as a candidate to suitably "in vitro" assess the effects of different drugs on various cell populations.

Keywords: Bioreactor; Poly-L-Lactic acid; fluid dynamic; phase separation; shear stress; vascular tissue engineering.