Mendonça da Silva, J;
Erro, E;
Awan, M;
Chalmers, SA;
Fuller, B;
Selden, C;
(2020)
Small-Scale Fluidized Bed Bioreactor for Long-Term Dynamic Culture of 3D Cell Constructs and in vitro Testing.
Frontiers in Bioengineering and Biotechnology
, 8
, Article 895. 10.3389/fbioe.2020.00895.
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Abstract
With the increasing interest in three-dimensional (3D) cell constructs that better represent native tissues, comes the need to also invest in devices, i.e., bioreactors, that provide a controlled dynamic environment similar to the perfusion mechanism observed in vivo. Here a laboratory-scale fluidized bed bioreactor (sFBB) was designed for hydrogel (i.e., alginate) encapsulated cells to generate a dynamic culture system that produced a homogenous milieu and host substantial biomass for long-term evolution of tissue-like structures and “per cell” performance analysis. The bioreactor design, conceptualized through scale-down empirical similarity rules, was initially validated through computational fluid dynamics analysis for the distributor capacity of homogenously dispersing the flow with an average fluid velocity of 4.596 × 10–4 m/s. Experimental tests then demonstrated a consistent fluidization of hydrogel spheres, while maintaining shape and integrity (606.9 ± 99.3 μm diameter and 0.96 shape factor). It also induced mass transfer in and out of the hydrogel at a faster rate than static conditions. Finally, the sFBB sustained culture of alginate encapsulated hepatoblastoma cells for 12 days promoting proliferation into highly viable (>97%) cell spheroids at a high final density of 27.3 ± 0.78 million cells/mL beads. This was reproducible across multiple units set up in parallel and operating simultaneously. The sFBB prototype constitutes a simple and robust tool to generate 3D cell constructs, expandable into a multi-unit setup for simultaneous observations and for future development and biological evaluation of in vitro tissue models and their responses to different agents, increasing the complexity and speed of R&D processes.
| Type: | Article |
|---|---|
| Title: | Small-Scale Fluidized Bed Bioreactor for Long-Term Dynamic Culture of 3D Cell Constructs and in vitro Testing |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fbioe.2020.00895 |
| Publisher version: | https://doi.org/10.3389/fbioe.2020.00895 |
| Language: | English |
| Additional information: | Copyright © 2020 Mendonça da Silva, Erro, Awan, Chalmers, Fuller and Selden. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | fluidized bed bioreactor, scale down model, 3D cell culture, cell encapsulation, hydrogel, alginate |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10110089 |
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