Coupling curvature-dependent and shear stress-stimulated neotissue growth in dynamic bioreactor cultures: a 3D computational model of a complete scaffold

Guyot, Yann; Papantoniou, Ioannis; Luyten, Frank P.; Geris, Liesbet

doi:10.1007/s10237-015-0753-2

Cited by 64 publications

(66 citation statements)

References 64 publications

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“…In engineered tissue scaffolds, tissue grown by osteoblastderived cells in pores of different shapes is also observed to be regulated by geometry. The local rate of growth is found to correlate with the curvature of the tissue [11][12][13], and thought to be due to tissue surface tension driving cell proliferation [12][13][14][15]. Phenomenological models that describe these scaffold experiments assume that the evolution of the tissue interface is governed by mean curvature flows, by analogy with surface-tension-induced mean curvature flows that arises in the evolution of bubbles in fluid mechanics.…”

Section: Discussionmentioning

confidence: 99%

“…There are many design questions that need to be addressed in the production of these scaffolds, such as determining their optimal size, shape and material properties [2][3][4]. These properties have been shown to impact cell attachment, viability, proliferation, migration, and differentiation, among other functions [10][11][12][13][14][15][16], and they could be tuned to control the manufacture of complex multicellular tissues or organs. Recent additive manufacturing techniques have leveraged these biophysical relationships in an ad hoc manner: by 3D printing bilayer cylindrical scaffolds as vascular grafts with endothelial and muscle cells [17] or by patterning scaffold pores or fibres * Corresponding author: pascal.buenzli@qut.edu.au to spatially control cell morphology and differentiation [18].…”

Section: Introductionmentioning

confidence: 99%

“…Several mathematical modelling strategies have been developed to explore the interplay between tissue growth and curvature effects [16], such as models based on the idea of mean curvature flow, that borrow ideas from fluid mechanics and the role of surface tension, but that do not consider cells explicitly [11][12][13][14][15]. Other modelling approaches consider the effects of cell-level behaviour and tissue crowding and spreading during surface growth, which lead to hyperbolic curvature flow models [24,22,25].…”

Section: Introductionmentioning

confidence: 99%

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Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Buenzli

Lanaro

Wong

et al. 2020

Preprint

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Tissue growth in bioscaffolds can be influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in a 3D printed scaffold by analysing experiments with a mathematical model. Experimentally, the new tissue infills the pore continually from the pore perimeter under strong curvature control, which leads to rounding off of the initial pore shape. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge the pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction-diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new cellular tissue in the model grows at a rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis therefore suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic cell proliferation and cell diffusion processes. The rates of these processes are unaffected by pore geometry, and can be predicted by simple reaction-diffusion models of cells that have robust, consistent behaviours.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Buenzli

Lanaro

Wong

et al. 2020

Preprint

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“…Unfortunately, however, the complex internal structure of the porous scaffolds makes estimation of the required shear stresses via experimental or analytical techniques impractical. Hence, computational fluid dynamics models, based on either idealized pore geometries 6,8,[16][17][18][19][20][21] or actual scaffold images, 12,[22][23][24][25][26][27][28][29][30][31][32][33][34] are commonly utilized.…”

Section: Introductionmentioning

confidence: 99%

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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“…The first paper in this series deals with the development of a computational modeling tool, which allows to better understand and control the growth process of in vitro cultured neotissues toward obtaining functional tissues (Guyot et al 2015). The second paper on orthopedics deals with finite-element simulations of the bone remodeling process of a femur implanted with a cementless total hip replacement and a hip resurfacing implant (Dickinson 2015).…”

mentioning

confidence: 99%

Foreword to the special issue on Bone and cartilage mechanobiology across the scales

Pivonka

Fernandez

Hunter

2016

Biomech Model Mechanobiol

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Coupling curvature-dependent and shear stress-stimulated neotissue growth in dynamic bioreactor cultures: a 3D computational model of a complete scaffold

Cited by 64 publications

References 64 publications

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

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

Foreword to the special issue on Bone and cartilage mechanobiology across the scales

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