An official website of the United States government
Abstract Due to the three-dimensional nature of the 3D bio-printed scaffolds, typical stagnant cell culturing methods don’t ensure entering medium inside areas or passing through the scaffolds. The bioreactor has frequently provided the required growth medium to encapsulated- and seeded-cells in 3D bio-printed scaffolds. To address this issue, we developed a customized perfusion bioreactor to supply the growth medium dynamically to the cells encapsulated or seeded in the scaffolds. The dynamic supply of fresh growth medium may help improve cell viability and proliferation. Because of its uniform nutrition distribution and flow-induced shear stress within the tissue-engineering scaffold, perfusion bioreactors have been used in a variety of tissue engineering applications. Including a modified setup of our designed bioreactor may improve the in vivo stimuli and conditions, eventually enhancing the overall performance of tissue regeneration. In this paper, we explored the response of fluid flow to certain types of scaffold pore geometries and porosities. We used a simulation technique to determine fluid flow turbulence through various pore geometries such as uniform triangular, square, diamond, circular, and honeycomb. We used variable pore sizes of the scaffold maintaining constant porosity to analyze the fluid flow. Based on the results, optimum designs for scaffolds were determined.
more »
« less
This content will become publicly available on November 17, 2025
A Computational Fluid Dynamics Model for Investigation of Material Flow in a Perfusion Bioreactor Toward Optimal Biomedical Design of Cell-Laden Scaffolds for Bone Regeneration
Abstract In tissue engineering, once a scaffold has completed mechanical property testing, it must then undergo biological characterization which determines if the scaffold is capable of supporting cell viability. To perform biological tests, cells must be seeded onto a scaffold with the help of bioreactors, the four main types being: (i) rotating wall, (ii) spinner flask, (iii) compression, and (iv) perfusion bioreactor. In perfusion bioreactors, a consistent flow of material is introduced (using a pump) into the inlet of the bioreactor chamber where multiple scaffolds of a disc geometry are located. However, the intrinsic, complex interaction between the scaffolds and material flow as it goes through the bioreactor chamber affects the viability of the seeded stem cells. Therefore, there is a need to identify consequential fluid dynamics phenomena governing the material flow in a perfusion bioreactor. In this study, using a CFD model, the effects of critical scaffold parameters (such as the number of scaffolds, scaffold diameter, scaffold thickness, and number of pores) on the main flow properties (i.e., flow pressure, wall shear stress, and streamline velocity) influential in cell proliferation and bone development will be investigated. It was observed that increasing the number of pores, in addition to decreasing the pore diameter had an adverse effect on the maximum forces occurring on the scaffold. In addition, changing the overall scaffold diameter did not appear to have as much as an effect as the other parameters. Furthermore, it was observed that a decrease in porosity would lead to an increase in wall shear stress and consequently in cell death. Overall, the outcomes of this study pave the way for optimal design, fabrication, and preparation of cell-laden bone scaffolds for treatment of bone fractures in clinical settings.
more »
« less
- Award ID(s):
- 2327460
- PAR ID:
- 10637384
- Publisher / Repository:
- American Society of Mechanical Engineers (ASME) - International Mechanical Engineering Congress and Exposition (IMECE 2024)
- Date Published:
- ISBN:
- 978-0-7918-8860-5
- Subject(s) / Keyword(s):
- Advanced Manufacturing Computational Fluid Dynamics (CFD) Bioreactors Bone Tissue Engineering.
- Format(s):
- Medium: X
- Location:
- Portland, Oregon, USA
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Three-dimensional (3D) bioprinting is a promising technique for creating patient-specific 3D scaffolds of tissues or organs. An appropriate culturing process is critical to confirm encapsulated and seeded cells’ excellent viability and proliferation into scaffolds materials. Traditional stagnant cell culturing methods don’t ensure entering medium inside areas or passing through the scaffolds. To resolve this issue, we developed a customized perfusion bioreactor to supply the growth medium dynamically to the encapsulated or seeded cells. Our custom-designed bioreactor improves the in vivo stimuli and conditions, which may enhance cell viability and proliferation performance. A design of a dual medium tank was utilized allowing the replacement of already-used medium without interrupting perfusion. Accommodating an array of cassettes in a newly designed perfusion chamber allowed a wide range of scaffolds with various size and shapers to hold. In this paper, we explored fluid flow response on scaffolds fabricated with various material compositions with different viscosities. We fabricated scaffolds following a 00–900 deposition pattern with 8% Alginate, 4% Alginate-4% Carboxymethyl Cellulose (CMC), and 2% Alginate-6% CMC incubated, allowing a constant fluid flow for various periods such as 1, 2, 4, and 8 hours. The change of scaffolds fabricated with multiple material compositions was determined in terms of swelling rate, i.e., change of filament width, and material diffusion, i.e., comparison of dry material weight before and after incubation. This comparative study can assist in application-based materials selection suitable for incubating in a perfusion bioreactor.more » « less
-
Babski-Reeves, K; Eksioglu, B; Hampton, D. (Ed.)Traditional static cell culture methods don't guarantee access to medium inside areas or through the scaffolds because of the complex three-dimensional nature of the 3D bio-printed scaffolds. The bioreactor provides the necessary growth medium encapsulated and seeded cells in 3D bioprinted scaffolds. The constant flow of new growing medium could promote more viable and multiplying cells. Therefore, we created a specialized perfusion bioreactor that dynamically supplies the growth medium to the cells implanted or encapsulated in the scaffolds. A redesigned configuration of our developed bioreactor may enhance the in vivo stimuli and circumstances, ultimately improving the effectiveness of tissue regeneration. This study investigated how different scaffold pore shapes and porosities affect the flow. We employed a simulation technique to calculate fluid flow turbulence across several pore geometries, including uniform triangular, square, circular, and honeycomb. We constructed a scaffold with changing pore diameters to examine the fluid movement while maintaining constant porosity. The impact of fluid flow was then determined by simulating and mimicking the architecture of bone tissue. The best scaffold designs were chosen based on the findings.more » « less
-
Abstract Cell-laden, scaffold-based tissue engineering methods have been successfully utilized for the treatment of bone fractures and diseases, caused by factors such as trauma, tumors, congenital anomalies, and aging. In such methods, the rate of scaffold biodegradation, transport of nutrients and growth factors, as well as removal of cell metabolic wastes at the site of injury are critical fluid-dynamics factors, affecting cell proliferation and ultimately tissue regeneration. Therefore, there is a critical need to identify the underlying material transport mechanisms and factors associated with cell-seeded, scaffold-based bone tissue engineering. The overarching goal of this study is to contribute to patient-specific, clinical treatment of bone pathology. The overall objective of the work is to establish computational fluid dynamics (CFD) models to identify: (i) the consequential mechanisms behind internal and external material transport through/over porous bone scaffolds and (ii) optimal triply periodic minimal surface (TPMS) scaffold designs toward cell-laden bone fracture treatment. In this study, 10 internal-flow and 10 external-flow CFD models were established using ANSYS, correspondingly based on 10 single-unit TPMS bone scaffold designs, where the geometry of each design was parametrically created using Rhinoceros 3D software. The influence of several design parameters, such as surface representation iteration, merged toggle iso value, and wall thickness, on geometry accuracy as well as computational time, was investigated in order to obtain computationally efficient and accurate CFD models. The fluid properties (such as density and dynamic viscosity) as well as the boundary conditions (such as no-slip condition, inlet flow velocity, and pressure outlet) of the CFD models were set based on clinical/research values reported in the literature as well as according to the fundamentals of internal/external Newtonian flow modeling. Several fluid characteristics, including flow velocity, flow pressure, and wall shear stress, were analyzed to observe material transport internally through and externally over the TPMS scaffold designs. Regarding the internal flow CFD modeling, it was observed that “P.W. Hybrid” (i.e., Design #7) had the highest-pressure output, with “Neovius” (i.e., Design #1) following second to it. These two designs have a relatively flatter surface area. In addition, “Schwarz P” (i.e., Design #2) was the lowest pressure output of all 10 TPMS designs. “Neovius” and “Schwarz P” had the highest and lowest values of wall shear stress. Besides, the velocity streamlines analysis showed an increase in velocity along the curved sections of the scaffolds’ geometry. Regarding the external flow CFD modeling, it was observed that “Neovius” yielded the highest-pressure output within the inlet section, which contains the area of the highest-pressure location. Furthermore, “Diamond” (i.e., Design #8) displayed having the highest values of wall shear stress due to the results of fluid interaction that accrues with complex curved structures. Also, when we look at designs like “Schwarz G”, the depiction of turbulent motion can be seen along the internal curved sections of the structure. As the external velocity streamlines decrease within the inner channels of the designs, this will lead to an increased pressure buildup due to the intrinsic interactions between the fluid with the walls. Overall, the outcomes of this study pave the way for optimal design and fabrication of complex, bone-like tissues with desired material transport properties for cell-laden, scaffold-based treatment of bone fractures.more » « less
-
Our study aims to identify the role of fluid flow in the growth of human bone cancer cells during metastasis. In our experiments, the cancer cells are seeded on the surface of cylindrical scaffolds in a bioreactor. The flow is laminar flow, which mimics the physiological conditions of the human body. A full-scale 3D high-resolution computational mesh of scaffold was created based on the physical scaffold's Micro-CT scans using open-source imaging software Slicer3D and Meshmixer. To investigate the influences of the flow on the seeded cells, we performed Computational Fluid Dynamics (CFD) simulations with the immersed boundary method (Gilmanov, Le, Sotiropoulos, JCP 300, 1, 2015). The computational domain was generated using the commercial software Gridgen. Our results show that the fluid flow velocity is highly dependent on the shape and pore sizes. In addition, the magnitude of the velocity on the surface where the cells are seeded is in between [0-0.05] μm/sallowing the cells to grow without being detached from the surface of the scaffold. Our future work will focus on (i) investigating the role of the shear stress on the distribution and orientation of the cancer cells. (ii) Simulating multiple scaffolds within the bioreactor to further quantify the impact of the gap on the flow velocity and shear.more » « less
