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1. A Simulation Approach to Determine Internal Architecture of 3D Bio-Printed Scaffold Suitable for A Perfusion Bioreactor

   Clark, S.; Quigley, C.; Mankowsky, J.; & Habib, M. A. (May 2023, Proceedings of the IISE Annual Conference & Expo 2023)

   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. 

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2. An Investigation on 3D Bio-Printed Scaffold Shape Fidelity Incubated in a Custom-Made Perfusion Bioreactor

   https://doi.org/10.1115/msec2023-104321  

   Mankowsky, Jack; Quigley, Connor; Clark, Scott; Habib, MD Ahasan (June 2023, American Society of Mechanical Engineers)

   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. 

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3. 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

   https://doi.org/10.1115/IMECE2024-139666  

   Rollins, Hannah; Salary, Roozbeh “Ross” (November 2024, American Society of Mechanical Engineers (ASME) - International Mechanical Engineering Congress and Exposition (IMECE 2024))

   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. 

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4. On the Impacts of Flow on the Migration and Growth of Cancer Cells

   https://doi.org/10.1115/dmd2022-1050  

   Akerkouch, Lahcen; Le, Trung; Jasuja, Haneesh; Katti, Kalpana; Katti, Dinesh (April 2022, Proceedings of the 2022 Design of Medical Devices Conference)

   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. 

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5. High-Fidelity Simulation of Flows in Bone-Like Environment to Investigate the Growth of Cancer Cells

   https://doi.org/10.1115/DMD2021-1081  

   Akerkouch, Lahcen; Le, Trung; Jasuja, Haneesh; Katti, Kalpana; Katti, Dinesh (April 2021, 2021 Design of Medical Devices Conference)

   Abstract Metastatic cancer in bones is incurable, which causes significant mobility and mortality to the patients. In this work, we investigate the role of interstitial fluid flow on cancer cells' growth within the interconnected pores of human bone. In-vitro experiments were carried out in a bio-reactor which includes bone-like scaffold specimens. A pump is used to maintain a laminar flow condition inside the bioreactor to resemble fluid flow in bones. The scaffold specimens are harvested after 23 days in the bioreactor. The scaffold specimen is scanned with Micro-CT under the resolution of 70 micrometers. We created a full-scale 3D computational model of the scaffold based on the micro-CT data using the open-source software Seg3D and Meshmixer. Based on the geometrical models, we generated the computational grids using the commercial software Gridgen. We performed Computational Fluid Dynamics (CFD) simulations with the immersed boundary method (Gilmanov, Le, Sotiropoulos, JCP 300, 1, 2015) to investigate the flow patterns inside the pores of the scaffolds. The results reveal a non-uniform flow distribution in the vicinity of the scaffold. The flow velocity and the shear stress distributions inside the scaffold are shown to be convoluted and very sensitive to the pore sizes. Our future work will further quantify these distributions and correlate them to cancer cells' growth observed in the experiments. 

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