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.

Solution-Based Processing for Scaffold Fabrication in Tissue Engineering Applications: A Brief Review

“…The TIPS technique is a commonly used method to fabricate TE scaffolds due to its simplicity and effectiveness in adjusting the structure and properties to the application of materials [70,74]. Carfì et al [101] combined TIPS and DIPS to produce a multifunctional scaffold with easy-tunable pore size, porosity, and thickness. In their study, a double-structured PLLA scaffold was prepared by performing TIPS around a vessel-like scaffold fabricated by DIPS, resulting in an embedded structure for mimicking a vascularized tissue.…”

Novel dual-flow perfusion bioreactor for in vitro pre-screening of nanoparticles delivery: design, characterization and testing

“…In this study, a dual-flow perfusion bioreactor, previously designed and built by our research group [42], was improved and characterized. It consists of two glass cylindrical tubes (a main column and a bubble column) connected to each other.…”

“…For this evaluation, a working range between 27 and 85 RPM was investigated. The flow rates analysis of IPC was extensively discussed in a previous work [42].…”

Engineering approaches in siRNA delivery

“…To this end, Carfì and coauthors developed a system able to mimic a vascularized biological tissue under physiological conditions (Carfì Pavia et al, 2017). The system is composed by a double flow perfusion bioreactor and a double structured scaffold ( Figure 6).…”