Computational modeling of media flow through perfusion-based bioreactors for bone tissue engineering

Abstract

Bioreactor system has been used in bone tissue engineering in order to simulate dynamic nature of bone tissue environments. Perfusion bioreactors have been reported as the most efficient types of shear-loading bioreactor. Also, combination of forces, such as rotation plus perfusion, has been reported to enhance cell growth and osteogenic differentiation. Mathematical modeling using sophisticated infrastructure processes could be helpful and streamline the development of functional grafts by estimating and defining an effective range of bioreactor settings for better augmentation of tissue engineering. This study is aimed to conduct computational modeling for newly designed bioreactors in order to alleviate the time and material consuming for evaluating bioreactor parameters and effect of fluid flow hydrodynamics (various amounts of shear stress) on osteogenesis. Also, biological assessments were performed in order to validate similar parameters under implementing the perfusion or rotating and perfusion fluid motions in bioreactors’ prototype. Finite element method was used to investigate the effect of hydrodynamic of fluid flow inside the bioreactors. The equations used in the simulation to calculate the velocity values and consequently the shear stress values include Navier–Stokes and Brinkman equations. It has been shown that rotational fluid motion in rotating and perfusion bioreactor produces more velocity and shear stress compared with perfusion bioreactor. Moreover, implementing the perfusion together with rotational force in rotating and perfusion bioreactors has been shown to have more cell proliferation and higher activity of alkaline phosphatase enzyme as well as formation of extra cellular matrix sheet, as an indicator of bone-like tissue formation.

Optimization and Validation of a Custom-Designed Perfusion Bioreactor for Bone Tissue Engineering: Flow Assessment and Optimal Culture Environmental Conditions

“…The tool has been applied in some tissue engineering studies, to examine microfluidics in bioreactor systems (Geris et al, 2016). In most cases, in silico modeling was performed using a simplified geometry (e.g., a cylinder), idealized by parameterization to reduce the computational burden (Zhao et al, 2019;Ramani-Mohan et al, 2018;Egger et al, 2017;Nokhbatolfoghahaei et al, 2020;Pereira et al, 2021;Melke et al, 2020). Parameterization with porosity and permeability allows the geometry to be considered as a porous domain to which Darcy flow model may be applied.…”

Perfused Platforms to Mimic Bone Microenvironment at the Macro/Milli/Microscale: Pros and Cons

“…Rotating bioreactors offer major advantages over spinner flasks since they also control the supply of oxygen and exert low fluid shear stress and turbulence ( Kimelman-Bleich et al, 2011 ; Weszl et al, 2012 ; Song et al, 2013 ; Shekaran et al, 2015 ; Song et al, 2016a ; Demir et al, 2018 ; Westman et al, 2019 ; Daulbayev et al, 2020 ; Nokhbatolfoghahaei et al, 2020a ; Nokhbatolfoghahaei et al, 2020b ; Nokhbatolfoghahaei et al, 2020c ). The most common rotating wall bioreactor is formed by two concentric cylinders: 1) the outer one is a culture chamber and accommodates the cellularized scaffold, submerged in culture medium, while 2) the inner cylinder is static and permits gas exchange ( Figure 1B ).…”

“…Among these, 3D in vitro fluidic macroscale (i.e., spinner flasks, rotating wall vessels), milliscale (customized perfusion bioreactors), and microscale systems (i.e., microfluidic devices) appear very promising to overcome the limitations of 2D cultures. These devices allow a fine tuning of dynamic interstitial perfusion ( Wittkowske et al, 2016 ; Yuste et al, 2021 ), a full understanding of cell-cell and cells-ECM interactions and, overall, a better comprehension of in vivo biological mechanisms ( Kim et al, 2007 ; Esch et al, 2015 ; Arrigoni et al, 2017 ; Carvalho et al, 2018 ; Wang et al, 2018 ; Nokhbatolfoghahaei et al, 2020a ). So far, good outcomes have been achieved in reproducing structural, functional, and mechanical properties of tissues using perfused platforms, including lung alveoli and bronchioles ( Huh et al, 2010 ; Ott et al, 2010 ; Price et al, 2010 ; Stucki et al, 2015 ), renal tubules and glomeruli ( Humes et al, 1999 ; Humes et al, 2004 ; Jang and Suh, 2010 ; Wilmer et al, 2016 ), small intestine ( Kimura et al, 2008 ; Imura et al, 2009 ; Pusch et al, 2011 ; Schweinlin et al, 2016 ), liver ( Kane et al, 2006 ; Tsang et al, 2007 ; Yamada et al, 2007 ; Domansky et al, 2010 ; Elbakary and Badhan, 2020 ) and the blood-brain barrier ( Booth and Kim, 2012 ; Griep et al, 2013 ).…”

Construction of spider silk protein small‐caliber tissue engineering vascular grafts based on dynamic culture and its performance evaluation

“…In an incubator, the combined blood vessel bioreactor can provide a relatively closed, non-toxic, sterile environment with adequate oxygen supply and stable temperature for vascular construction. 22,23 first reported the successful construction of tissue-engineered small vessels using a blood vessel bioreactor in 1999. The findings revealed that the vessels' morphology and histology were comparable to that of native blood vessels.…”

“…As a result, the researchers designed blood vessel bioreactor, which could simulate the throbbing of blood vessels circulating in the body, and successfully used it to construct TEVG. In an incubator, the combined blood vessel bioreactor can provide a relatively closed, non‐toxic, sterile environment with adequate oxygen supply and stable temperature for vascular construction 22,23 . Niklason et al first reported the successful construction of tissue‐engineered small vessels using a blood vessel bioreactor in 1999.…”