Solid stress generated by spheroid growth estimated using a linear poroelasticity model☆

Roose, Tiina; Netti, Paolo A.; Munn, Lance L.; Boucher, Yves; Jain, Rakesh K.

doi:10.1016/s0026-2862(03)00057-8

Cited by 273 publications

(270 citation statements)

References 19 publications

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“…Linear and weakly nonlinear analyses have been performed to assess the stability of spherical tumors to asymmetric perturbations (e.g., Chaplain et al (2001), Byrne and Matthews (2002), Cristini et al (2003), and Li et al (2006), and discussed in the reviews by Araujo and McElwain (2004a) and Byrne et al (2006)) as a means to characterize the degree of aggression. Various interactions of the tumor with the microenvironment, such as stress-induced limitations of tumor growth, have also been studied in this context (e.g., Jones et al (2000), Mollica (2002, 2004), Roose et al (2003), McElwain (2004b, 2005), and Ambrosi and Guana (2006)). Most of the previous modeling has considered single-phase tumors.…”

Section: Introductionmentioning

confidence: 99%

Nonlinear simulation of the effect of microenvironment on tumor growth

Macklin

Lowengrub

2007

Journal of Theoretical Biology

176

190

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In this paper, we present and investigate a model for solid tumor growth that incorporates features of the tumor microenvironment. Using analysis and nonlinear numerical simulations, we explore the effects of the interaction between the genetic characteristics of the tumor and the tumor microenvironment on the resulting tumor progression and morphology. We find that the range of morphological responses can be placed in three categories that depend primarily upon the tumor microenvironment: tissue invasion via fragmentation due to a hypoxic microenvironment; fingering, invasive growth into nutrient-rich, biomechanically unresponsive tissue; and compact growth into nutrient-rich, biomechanically responsive tissue. We found that the qualitative behavior of the tumor morphologies was similar across a broad range of parameters that govern the tumor genetic characteristics. Our findings demonstrate the importance of the impact of microenvironment on tumor growth and morphology and have important implications for cancer therapy. In particular, if a treatment impairs nutrient transport in the external tissue (e.g., by anti-angiogenic therapy), increased tumor fragmentation may result, and therapy-induced changes to the biomechanical properties of the tumor or the microenvironment (e.g., antiinvasion therapy) may push the tumor in or out of the invasive fingering regime.

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Section: Introductionmentioning

confidence: 99%

Nonlinear simulation of the effect of microenvironment on tumor growth

Macklin

Lowengrub

2007

Journal of Theoretical Biology

176

190

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“…Linear and weakly nonlinear analyses have been performed to assess the stability of spherical tumors to asymmetric perturbations [49,42,59,127,16,37] in order to characterize the degree of aggression. Various interactions of a tumor with the microenvironment, such as stress-induced limitations to growth, have also been studied [108,6,7,176,17,18,5]. Most of the modeling has considered single-phase (e.g., single cell species) tumors, although multiphase mixture models have also been developed to provide a more detailed account of tumor heterogeneity [7,43,50].…”

Section: Introductionmentioning

confidence: 99%

Nonlinear Modeling and Simulation of Tumor Growth

Cristini

Frieboes

et al. 2008

Selected Topics in Cancer Modeling

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“…Important further work includes explicit modelling of the mechanical properties of the scaffold and ECM, considering, for example, a poroelastic (Roose et al, 2003) or poroviscoelastic (Byrne and Preziosi, 2003) model. Additionally, the robustness of our conclusions should be investigated by considering the addition of nutrientlimited growth to our formulation; methodologies for such investigations are given by Lewis et al (2005) and Lemon and King (2007).…”

Section: Discussionmentioning

confidence: 99%

“…Stimuli relevant to tissue engineering applications include contact inhibition, residual stress caused by tissue growth (Fung, 1991;Skalak et al, 1996;Roose et al, 2003;Chaplain et al, 2006;Holzapfel and Ogden, 2006) and the local fluid dynamics, such as the local hydrostatic pressure or fluid shear stress (You et al, 2000(You et al, , 2001Bakker et al, 2004a;Han et al, 2004;Yourek et al, 2004).…”

Section: Mechanotransduction-mediated Growthmentioning

confidence: 99%

The interplay between tissue growth and scaffold degradation in engineered tissue constructs

et al. 2012

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In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation.In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (i) differential interactions between cells and the supporting scaffold and their associated ECM, (ii) scaffold degradation, and (iii) mechanotransduction-regulated cell proliferation and ECM deposition.Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from µCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of engineered tissue constructs and their suitability for implantation in vivo.

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Solid stress generated by spheroid growth estimated using a linear poroelasticity model☆

Cited by 273 publications

References 19 publications

Nonlinear simulation of the effect of microenvironment on tumor growth

Nonlinear simulation of the effect of microenvironment on tumor growth

Nonlinear Modeling and Simulation of Tumor Growth

The interplay between tissue growth and scaffold degradation in engineered tissue constructs

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