Mathematical and numerical modeling of an airlift perfusion bioreactor for tissue engineering applications

• Published in: Biochemical engineering journal 2022-01, Vol.178, p.108298, Article 108298
• Main Authors: Capuana, Elisa, Carfì Pavia, Francesco, Lombardo, Maria Elena, Rigogliuso, Salvatrice, Ghersi, Giulio, La Carrubba, Vincenzo, Brucato, Valerio
• Format: Article
• Language: English
• Subjects: Computational fluid dynamics simulation; Dynamic cell culture; Flow rate and mass transport mathematical model; Tissue engineering
• ISSN: 1369-703X; 1873-295X
• DOI: 10.1016/j.bej.2021.108298

The Tissue Engineering (TE) strategy is widely focused on the development of perfusion bioreactors to promote the production of three-dimensional (3D) functional tissues. To optimize tissue production, it is worth investigating the engineering parameters of a bioreactor system for identifying a beneficial range of operation variables. Mathematical and numerical modeling of a perfusion bioreactor is capable to provide relevant insights into the fluid flow and nutrients transport while predicting experimental data and exploring the impact of changing operating parameters, such as fluid velocities. In this work, the hydrodynamic parameters and oxygen transport were investigated using mathematical equations and Computational Fluid Dynamics (CFD) analysis modeling on a novel perfusion bioreactor working as an airlift external loop. Mathematical models and numerical simulation were associated with experimental results at different configurations to evaluate the effect of the reactor parameters on its hydrodynamics. All predictions of gas holdup and liquid circulation velocity from the modeling were in good agreement with the experimental data. A Poly-L-lactic acid (PLLA) scaffold was produced by Thermally Induced Phase Separation (TIPS) and used as 3D support for biological tests in static and dynamic conditions to assess cell viability and proliferation inside the bioreactor. The whole set of fluid-dynamic and biological results showed that our bioreactor environment offers the benefits of an in vitro potential system to produce functional engineered tissues. [Display omitted] •An airlift bioreactor for Tissue Engineering applications was developed and validated.•A simple mathematical model under bubbly flow regime was used for airlift bioreactor analysis.•CFD simulation was useful for the optimization of bioreactor design and hydrodynamic performance.•A liquid distributor introduced in the optimized design supports a uniform profile of liquid velocity.•The designed airlift perfusion bioreactor improves 3D cell growth compared to static culture.