A comparative study of shear stresses in collagen-GAG and calcium phosphate scaffolds in bone tissue-engineering bioreactors (original) (raw)
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Tissue Engineering Part A, 2009
The increasing demand for bone grafts combined with their limited availability and potential risks has led to much new research in bone tissue engineering. Current strategies of bone tissue engineering commonly utilize cell-seeded scaffolds and flow perfusion bioreactors to stimulate the cells to produce bone tissue suitable for implantation into the patient's body. The aim of this study was to quantify and compare the wall shear stresses in two bone tissue engineering scaffold types (collagen-GAG and calcium phosphate) exposed to fluid flow in a perfusion bioreactor. Based on µCT images, 3D numerical CFD models of the two scaffold types were developed to calculate the wall shear stresses within the scaffolds. For a given flow rate (normalized by the cross-sectional area of the scaffolds), shear stress is 2.8-fold higher in the Tissue Engineering F o r P e e r R e v i e w
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Flow perfusion bioreactors have been extensively investigated as a promising culture method for bone tissue engineering, due to improved nutrient delivery and shear force-mediated osteoblastic differentiation. However, a major drawback impeding the transition to clinically-relevant tissue regeneration is the inability to non-destructively monitor constructs during culture. To alleviate this shortcoming, we investigated the distribution of fluid shear forces in scaffolds cultured in flow perfusion bioreactors using computational fluid dynamic techniques, analyzed the effects of scaffold architecture on the shear forces and monitored tissue mineralization throughout the culture period using microcomputed tomography. For this study, we dynamically seeded one million adult rat mesenchymal stem cells (MSCs) on 85% porous poly(L-lactic acid) (PLLA) polymeric spunbonded scaffolds. After taking intermittent samples over 16 days, the constructs were imaged and reconstructed using microcomputed tomography. Fluid dynamic simulations were performed using a custom in-house lattice Boltzmann program. By taking samples at different time points during culture, we are able to monitor the mineralization and resulting changes in flow-induced shear distributions in the porous scaffolds as the constructs mature into bone tissue engineered constructs, which has not been investigated previously in the literature. From the work conducted in this study, we proved that the average shear stress per construct consistently increases as a function of culture time, resulting in an increase at Day 16 of 113%.
Medical Engineering & Physics, 2009
Tissue-engineered bone shows promise in meeting the huge demand for bone grafts caused by up to 4 million bone replacement procedures per year, worldwide. State-of-the-art bone tissue engineering strategies use flow perfusion bioreactors to apply biophysical stimuli to cells seeded on scaffolds and to grow tissue suitable for implantation into the patient's body. The aim of this study was to quantify the deformation of cells seeded on a collagen-GAG scaffold which was perfused by culture medium inside a flow perfusion bioreactor. Using a µCT scan of an unseeded collagen-GAG scaffold, a sequential 3D CFD-deformation model was developed. The wall shear stress and the hydrostatic wall pressure acting on the cells were computed through the use of a CFD simulation and fed into a linear elastostatics model in order to calculate the deformation of the cells. The model used numerically seeded cells of two common morphologies where cells are either attached flatly on the scaffold wall or bridging two struts of the scaffold. Our study showed that the displacement of the cells is primarily determined by the cell morphology. Although cells of both attachment profiles were subjected to the same mechanical load, cells bridging two struts experienced a deformation up to 500 times higher than cells only attached to one strut. As the scaffold's pore size determines both the mechanical load and the type of attachment, the design of an optimal scaffold must take into account the interplay of these two features and requires a design process that optimizes both parameters at the same time.
Regenerative Biomaterials
In the field of bone tissue engineering, particular interest is devoted to the development of 3D cultures to study bone cell proliferation under conditions similar to in vivo ones, e.g. by artificially producing mechanical stresses promoting a biological response (mechanotransduction). Of particular relevance in this context are the effects generated by the flow shear stress, which governs the nutrients delivery rate to the growing cells and which can be controlled in perfusion reactors. However, the introduction of 3D scaffolds complicates the direct measurement of the generated shear stress on the adhered cells inside the matrix, thus jeopardizing the potential of using multi-dimensional matrices. In this study, an anisotropic hydroxyapatite-based set of scaffolds is considered as a 3D biomimetic support for bone cells deposition and growth. Measurements of sample-specific flow resistance are carried out using a perfusion system, accompanied by a visual characterization of the mat...
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The use of biocompatible and biodegradable porous scaffolds produced via additive manufacturing is one of the most common approaches in tissue engineering. The geometric design of tissue engineering scaffolds (e.g., pore size, pore shape, and pore distribution) has a significant impact on their biological behavior. Fluid flow dynamics are important for understanding blood flow through a porous structure, as they determine the transport of nutrients and oxygen to cells and the flushing of toxic waste. The aim of this study is to investigate the impact of the scaffold architecture, pore size and distribution on its biological performance using Computational Fluid Dynamics (CFD). Different blood flow velocities (BFV) induce wall shear stresses (WSS) on cells. WSS values above 30 mPa are detrimental to their growth. In this study, two scaffold designs were considered: rectangular scaffolds with uniform square pores (300, 350, and 450 µm), and anatomically designed circular scaffolds wit...
SN Applied Sciences, 2021
The use of porous 3D scaffolds for the repair of bone nonunion and osteoporotic bone is currently an area of great interest. Using a combination of thermally-induced phase separation (TIPS) and 3D-plotting (3DP), we have generated hierarchical 3DP/TIPS scaffolds made of poly(lactic-co-glycolic acid) (PLGA) and nanohydroxyapatite (nHA). A full factorial design of experiments was conducted, in which the PLGA and nHA compositions were varied between 6‒12% w/v and 10‒40% w/w, respectively, totaling 16 scaffold formulations with an overall porosity ranging between 87%‒93%. These formulations included an optimal scaffold design identified in our previous study. The internal structures of the scaffolds were examined using scanning electron microscopy and microcomputed tomography. Our optimal scaffold was seeded with MC3T3-E1 murine preosteoblastic cells and subjected to cell culture inside a tissue culture dish and a perfusion bioreactor. The results were compared to those of a commercial ...
Journal of Biomechanics, 2010
An analytical model of the fluid/cell mechanical interaction was developed. The interfacial shear stress, due to the coupling between the fluid and the cell deformation, was characterized by a new dimensionless number N fs . For N fs above a critical value, the fluid/cell interaction had a damping effect on the interfacial shear stress. Conversely, for N fs below this critical value, interfacial shear stress was amplified. As illustration, the role of the dynamic fluid/cell mechanical coupling was studied in a specific biological situation involving cells seeded in a bone scaffold. For the particular bone scaffold chosen, the dimensionless number N fs was higher than the critical value. In this case, the dynamic shear stress at the fluid/cell interface is damped for increasing excitation frequency. Interestingly, this damping effect is correlated to the pore diameter of the scaffold, furnishing thus target values in the design of the scaffold. Correspondingly, an efficient cell stimulation might be achieved with a scaffold of pore size larger than 300 mm as no dynamic damping effect is likely to take place. The analytical model proposed in this study, while being a simplification of a fluid/cell mechanical interaction, brings complementary insights to numerical studies by analyzing the effect of different physical parameters.
Challenges in computational fluid dynamics applications for bone tissue engineering
Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, 2022
Bone injuries or defects that require invasive surgical treatment are a serious clinical issue, particularly when it comes to treatment success and effectiveness. Accordingly, bone tissue engineering (BTE) has been researching the use of computational fluid dynamics (CFD) analysis tools to assist in designing optimal scaffolds that better promote bone growth and repair. This paper aims to offer a comprehensive review of recent studies that use CFD analysis in BTE. The mechanical and fluidic properties of a given scaffold are coupled to each other via the scaffold architecture, meaning an optimization of one may negatively affect the other. For example, designs that improve scaffold permeability normally result in a decreased average wall shear stress. Linked with these findings, it appears there are very few studies in this area that state a specific application for their scaffolds and those that do are focused on in vitro bioreactor environments. Finally, this review also demonstra...
International Journal for Numerical Methods in Biomedical Engineering
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. 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). 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. 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. Overall, this work provides a previously-unavailable guidance to researchers regarding the best choice of boundary conditions for RVE simulations. Furthermore, it lays down the foundation for recovering more accurate scaffold stress estimates from the RVE approximations.
Mechanical interaction between cells and fluid for bone tissue engineering scaffold
An analytical model of the fluid/cell mechanical interaction was developed. The interfacial shear stress, due to the coupling between the fluid and the cell deformation, was characterized by a new dimensionless number N fs . For N fs above a critical value, the fluid/cell interaction had a damping effect on the interfacial shear stress. Conversely, for N fs below this critical value, interfacial shear stress was amplified. As illustration, the role of the dynamic fluid/cell mechanical coupling was studied in a specific biological situation involving cells seeded in a bone scaffold. For the particular bone scaffold chosen, the dimensionless number N fs was higher than the critical value. In this case, the dynamic shear stress at the fluid/cell interface is damped for increasing excitation frequency. Interestingly, this damping effect is correlated to the pore diameter of the scaffold, furnishing thus target values in the design of the scaffold. Correspondingly, an efficient cell stimulation might be achieved with a scaffold of pore size larger than 300 mm as no dynamic damping effect is likely to take place. The analytical model proposed in this study, while being a simplification of a fluid/cell mechanical interaction, brings complementary insights to numerical studies by analyzing the effect of different physical parameters.