Image-based modeling: A novel tool for realistic simulations of artificial bone cultures

Alam, Taseen A.; Pham, Quang Long; Sikavitsas, Vassilios I.; Papavassiliou, Dimitrios V.; Shambaugh, Robert L.; Voronov, Roman S.

doi:10.1142/s233954781620003x

Cited by 16 publications

(21 citation statements)

References 19 publications

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“…Over the last 10 years, nondestructive three‐dimensional image‐based technology has made steady progress (i.e., the ability to visualize micrometric objects) . The notion of virtual histology, which involves a combination of tomography imaging and image processing to analyse 3D tissue‐engineered emerged over this period . Among these technologies, high‐resolution X‐ray micro‐tomography offers noninvasive 3D visualization of biological scaffolds .…”

Section: Discussionmentioning

confidence: 99%

“…CFD approaches have shown promising results to estimate WSS distribution in idealized geometries and numerically reconstructed scaffold geometry from X‐ray tomography . To date, this strategy has been implemented with considerable success on single scaffold with a single‐cell resolution without contrast agent . This approach enables the assessment of cell proliferation (and mineralization) within the volume of 3D scaffolds.…”

Section: Discussionmentioning

confidence: 99%

“…Many researches have attempted to use micro‐computed tomography (μCT) to determine porosity or other characteristics within the scaffold as an alternative to histology. This technique allows for visualization and quantification of dense structures, and includes the possibility of investigating the influence of scaffold features, such as the internal pore architecture with regard to the growth of cells within the scaffold . Authors have previously reported that μCT can be used to image and segment microporous scaffolds seeded with mesenchymal stem cells (MSCs) and cultured to produce soft tissue and mineralized tissue in a bioreactor with a high degree of accurancy .…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, image processing is a key factor in establishing a relevant method for separating different phases (porosity, cells and biomaterials) from μCT images . Authors managed to segment images using an in‐house segmentation algorithm . 3D‐μCT reconstructions can be used to simulate flow and model the relationship between cell proliferation and mechanical quantities, including shear stress.…”

Section: Introductionmentioning

confidence: 99%

“…This technique allows for visualization and quantification of dense structures, and includes the possibility of investigating the influence of scaffold features, such as the internal pore architecture with regard to the growth of cells within the scaffold. [26][27][28][29][30] Authors have previously reported that μCT can be used to image and segment microporous scaffolds seeded with mesenchymal stem cells (MSCs) and cultured to produce soft tissue and mineralized tissue in a bioreactor with a high degree of accurancy. 28,30 Furthermore, image processing is a key factor in establishing a relevant method for separating different phases (porosity, cells and biomaterials) from μCT images.…”

mentioning

confidence: 99%

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Assessment of the interplay between scaffold geometry, induced shear stresses, and cell proliferation within a packed bed perfusion bioreactor

Thibeaux

Duval

Smaniotto

et al. 2019

Biotechnology Progress

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By favoring cell proliferation and differentiation, perfusion bioreactors proved efficient at optimizing cell culture. The aim of this study was to quantify cell proliferation within a perfusion bioreactor and correlate it to the wall shear stress (WSS) distribution by combining 3‐D imaging and computational fluid dynamics simulations.NIH‐3T3 fibroblasts were cultured onto a scaffold model made of impermeable polyacetal spheres or Polydimethylsiloxane cubes. After 1, 2, and 3 weeks of culture, constructs were analyzed by micro‐computed tomography (μCT) and quantification of cell proliferation was assessed. After 3 weeks, the volume of cells was found four times higher in the stacking of spheres than in the stacking of cube.3D‐μCT reconstruction of bioreactors was used as input for the numerical simulations. Using a lattice‐Boltzmann method, we simulated the fluid flow within the bioreactors. We retrieved the WSS distribution (PDF) on the scaffolds surface at the beginning of cultivation and correlated this distribution to the local presence of cells after 3 weeks of cultivation. We found that the WSS distributions strongly differ between spheres and cubes even if the porosity and the specific wetted area of the stackings were very similar. The PDF is narrower and the mean WSS is lower for cubes (11 mPa) than for spheres (20 mPa). For the stacking of spheres, the relative occupancy of the surface sites by cells is maximal when WSS is greater than 20 mPa. For cubes, the relative occupancy is maximal when the WSS is lower than 10 mPa. The discrepancies between spheres and cubes are attributed to the more numerous sites in stacking of spheres that may induce 3‐D (multi‐layered) proliferation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Assessment of the interplay between scaffold geometry, induced shear stresses, and cell proliferation within a packed bed perfusion bioreactor

Thibeaux

Duval

Smaniotto

et al. 2019

Biotechnology Progress

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Numerical accuracy comparison of two boundary conditions commonly used to approximate shear stress distributions in tissue engineering scaffolds cultured under flow perfusion

Kadri

Williams

Sikavitsas

et al. 2018

Numer Methods Biomed Eng

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Introduction Flow‐induced shear stresses have been found to be a stimulatory factor in pre‐osteoblastic cells seeded in 3D porous scaffolds and cultured under continuous flow perfusion. However, due to the complex internal structure of the scaffolds, whole scaffold calculations of the local shear forces are computationally intensive. Instead, representative volume elements (RVEs), which are obtained by extracting smaller portions of the scaffold, are commonly used in literature without a numerical accuracy standard. Objective Hence, the goal of this study is to examine how closely the whole scaffold simulations are approximated by the two types of boundary conditions used to enable the RVEs: “wall boundary condition” (WBC) and “periodic boundary condition” (PBC). Method To that end, lattice Boltzmann method fluid dynamics simulations were used to model the surface shear stresses in 3D scaffold reconstructions, obtained from high‐resolution microcomputed tomography images. Results It was found that despite the RVEs being sufficiently larger than 6 times the scaffold pore size (which is the only accuracy guideline found in literature), the stresses were still significantly under‐predicted by both types of boundary conditions: between 20% and 80% average error, depending on the scaffold's porosity. Moreover, it was found that the error grew with higher porosity. This is likely due to the small pores dominating the flow field, and thereby negating the effects of the unrealistic boundary conditions, when the scaffold porosity is small. Finally, it was found that the PBC was always more accurate and computationally efficient than the WBC. Therefore, it is the recommended type of RVE.

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Histological Method to Study the Effect of Shear Stress on Cell Proliferation and Tissue Morphology in a Bioreactor

Chabanon

Duval

Grenier

et al. 2019

Tissue Eng Regen Med

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BACKGROUND: Tissue engineering represents a promising approach for the production of bone substitutes. The use of perfusion bioreactors for the culture of bone-forming cells on a three-dimensional porous scaffold resolves mass transport limitations and provides mechanical stimuli. Despite the recent and important development of bioreactors for tissue engineering, the underlying mechanisms leading to the production of bone substitutes remain poorly understood. METHODS: In order to study cell proliferation in a perfusion bioreactor, we propose a simplified experimental setup using an impermeable scaffold model made of 2 mm diameter glass beads on which mechanosensitive cells, NIH-3T3 fibroblasts are cultured for up to 3 weeks under 10 mL/min culture medium flow. A methodology combining histological procedure, image analysis and analytical calculations allows the description and quantification of cell proliferation and tissue production in relation to the mean wall shear stress within the bioreactor. RESULTS: Results show a massive expansion of the cell phase after 3 weeks in bioreactor compared to static control. A scenario of cell proliferation within the three-dimensional bioreactor porosity over the 3 weeks of culture is proposed pointing out the essential role of the contact points between adjacent beads. Calculations indicate that the mean wall shear stress experienced by the cells changes with culture time, from about 50 mPa at the beginning of the experiment to about 100 mPa after 3 weeks. CONCLUSION: We anticipate that our results will help the development and calibration of predictive models, which rely on estimates and morphological description of cell proliferation under shear stress.

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Image-based modeling: A novel tool for realistic simulations of artificial bone cultures

Cited by 16 publications

References 19 publications

Assessment of the interplay between scaffold geometry, induced shear stresses, and cell proliferation within a packed bed perfusion bioreactor

Assessment of the interplay between scaffold geometry, induced shear stresses, and cell proliferation within a packed bed perfusion bioreactor

Numerical accuracy comparison of two boundary conditions commonly used to approximate shear stress distributions in tissue engineering scaffolds cultured under flow perfusion

Histological Method to Study the Effect of Shear Stress on Cell Proliferation and Tissue Morphology in a Bioreactor

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