Computational evaluation of oxygen and shear stress distributions in 3D perfusion culture systems: Macro-scale and micro-structured models

Cioffi, Margherita; Küffer, J.; Ströbel, Simon; Dubini, Gabriele; Martin, Ivan; Wendt, David

doi:10.1016/j.jbiomech.2008.07.023

Cited by 91 publications

(87 citation statements)

References 24 publications

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“…We measured an average drop of 10.5% in oxygen concentration between the inlet and outlet of the perfused construct. This value was compared with those reported by the only previous experimental study on interstitial perfusion (4). In their work they measured an oxygen drop of 55%, noticeably higher than our value.…”

Section: Discussionsupporting

confidence: 63%

Oxygen Measurement in Interstitially Perfused Cellularized Constructs Cultured in a Miniaturized Bioreactor

Raimondi

Giordano

Pietrabissa

2015

Journal of Applied Biomaterials & Functional Materials

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ORIGINAL ARTICLEered that three-dimensional (3D) scaffolds offer the possibility of culturing higher cell densities, support visualization, and resemble the biological environments more efficiently than the two-dimensional (2D) monolayer (2). In bioreactors, 3D scaffolds are positioned inside a culture chamber and are perfused with a culture medium which ensures the convective transport of solutes (O 2 , metabolites, catabolites, etc.) to and from the superficial regions of the construct.The success of bioreactor culture widely depends on oxygen gradient within the scaffold as oxygen plays an important role in various cell functions. Oxygen is required for the aerobic metabolism of carbon compounds and consequently impacts cell growth rate and protein synthesis; furthermore, it enhances the correct differentiation of stem cells. In constructs perfused only superficially, the resulting oxygen distribution is not homogeneous throughout the 3D construct volume because of the lack of interstitial flow and due to the low solubility of oxygen in the culture medium (3), which may lead to hypoxia. The presence of a better quantified local oxygenation is a condition required to avoid areas of hypoxia and to better control cell response in the cultured cellular constructs.Different methods have been employed in order to quantify oxygen consumption and concentration drop in 3D

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Section: Discussionsupporting

confidence: 63%

Oxygen Measurement in Interstitially Perfused Cellularized Constructs Cultured in a Miniaturized Bioreactor

Raimondi

Giordano

Pietrabissa

2015

Journal of Applied Biomaterials & Functional Materials

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“…4. The extension of the computational algorithms to treat a fully three-dimensional representation of the scaffold pore to allow a deeper model validation against previous existing simulation results and experimental data (see, e.g., [19,34,56]). In particular, a 3D implementation of the model could provide a very interesting in silico scheme to simulate different levels of isotropy/anisotropy that otherwise should be reproduced in vitro at the price of complex engineering strategies, as described in [34].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

A poroelastic mixture model of mechanobiological processes in biomass growth: theory and application to tissue engineering

et al. 2017

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In this article we propose a novel mathematical description of biomass growth that combines poroelastic theory of mixtures and cellular population models. The formulation, potentially applicable to general mechanobiological processes, is here used to study the engineered cultivation in bioreactors of articular chondrocytes, a process of Regenerative Medicine characterized by a complex interaction among spatial scales (from nanometers to centimeters), temporal scales (from seconds to weeks) and biophysical phenomena (fluid-controlled nutrient transport, delivery and consumption; mechanical deformation of a multiphase porous medium). The principal contribution of this research is the inclusion of the concept of cellular ''force isotropy'' as one of the main factors influencing cellular activity. In this description, the induced cytoskeletal tensional states trigger signalling transduction cascades regulating functional cell behavior. This mechanims is modeled by a parameter which estimates the influence of local force isotropy by the norm of the deviatoric part of the total stress tensor. According to the value of the estimator, isotropic mechanical conditions are assumed to be the promoting factor of extracellular matrix production whereas anisotropic conditions are assumed to promote cell proliferation. The resulting mathematical formulation is a coupled system of nonlinear partial differential equations comprising: conservation laws for mass and linear momentum of the growing biomass; advection-diffusion-reaction laws for nutrient (oxygen) transport, delivery and consumption; and kinetic laws for cellular population dynamics. To develop a reliable computational tool for the simulation of the engineered tissue growth process the nonlinear differential problem is numerically solved by: (1) temporal semidiscretization; (2) linearization via a fixed-point map; and (3) finite element spatial approximation. The biophysical accuracy of the mechanobiological model is assessed in the analysis of a simplified 1D geometrical setting. Simulation results show that: (1) isotropic/anisotropic conditions are strongly influenced by both maximum cell specific growth rate and mechanical boundary 123Meccanica (2017) 52: 3273-3297 DOI 10.1007/s11012-017-0638-9 conditions enforced at the interface between the biomass construct and the interstitial fluid; (2) experimentally measured features of cultivated articular chondrocytes, such as the early proliferation phase and the delayed extracellular matrix production, are well described by the computed spatial and temporal evolutions of cellular populations.

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“…In future applications, both the design of new perfusion bioreactors and the optimization of their operating conditions will derive significant benefits from computational fluid dynamics (CFD) modeling aimed at estimating fluid velocity and shear profiles, [37][38][39] as well as biochemical-species concentrations within the pores of 3D scaffolds. [40] A more comprehensive strategy that could help to elucidate and decouple the effects of mechanical stimuli and specific chemical species should i) combine theoretical and experimental approaches, that is, validate simplified models with experimental data, [41] and ii) use sensing and process-control systems to monitor and control specific culture parameters. The key contribution of these strategies for bioreactor-based TE procedures will be discussed in Section 3.…”

Section: Maintenance Of a Controlled Culture Environmentmentioning

confidence: 99%

“…Recently, microscale CFD models have been developed, based on microcomputed tomography (mCT) reconstructions of the 3D scaffolds, to predict local velocity and shear profiles throughout the actual pore microarchitecture of perfused scaffolds. [37,[39][40][41]83] Interestingly, simulations of flow through a foam scaffold having high pore interconnectivities, which were based on either a mCT model [37] or a simplified geometry model, [82] predicted similar globally averaged shear stresses. On the other hand, simulations based on the mCT-based model could reveal a more variable local shear distribution within individual pores and among different pores throughout the foam (Fig.…”

Section: S]so 4 and [mentioning

confidence: 99%

Potential and Bottlenecks of Bioreactors in 3D Cell Culture and Tissue Manufacturing

et al. 2009

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Over the last decade, we have witnessed an increased recognition of the importance of 3D culture models to study various aspects of cell physiology and pathology, as well as to engineer implantable tissues. As compared to well-established 2D cell-culture systems, cell/tissue culture within 3D porous biomaterials has introduced new scientific and technical challenges associated with complex transport phenomena, physical forces, and cell-microenvironment interactions. While bioreactor-based 3D model systems have begun to play a crucial role in addressing fundamental scientific questions, numerous hurdles currently impede the most efficient utilization of these systems. We describe how computational modeling and innovative sensor technologies, in conjunction with well-defined and controlled bioreactor-based 3D culture systems, will be key to gain further insight into cell behavior and the complexity of tissue development. These model systems will lay a solid foundation to further develop, optimize, and effectively streamline the essential bioprocesses to safely and reproducibly produce appropriately scaled tissue grafts for clinical studies.

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Computational evaluation of oxygen and shear stress distributions in 3D perfusion culture systems: Macro-scale and micro-structured models

Cited by 91 publications

References 24 publications

Oxygen Measurement in Interstitially Perfused Cellularized Constructs Cultured in a Miniaturized Bioreactor

Oxygen Measurement in Interstitially Perfused Cellularized Constructs Cultured in a Miniaturized Bioreactor

A poroelastic mixture model of mechanobiological processes in biomass growth: theory and application to tissue engineering

Potential and Bottlenecks of Bioreactors in 3D Cell Culture and Tissue Manufacturing

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