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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)

   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. Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas

   https://doi.org/10.3390/fluids7070222  

   Wang, Yifan ; Čanić, Sunčica ; Bukač, Martina ; Blaha, Charles ; Roy, Shuvo ( July 2022 , Fluids)

   We present a multi-scale mathematical model and a novel numerical solver to study blood plasma flow and oxygen concentration in a prototype model of an implantable Bioartificial Pancreas (iBAP) that operates under arteriovenous pressure differential without the need for immunosuppressive therapy. The iBAP design consists of a poroelastic cell scaffold containing the healthy transplanted cells, encapsulated between two semi-permeable nano-pore size membranes to prevent the patient’s own immune cells from attacking the transplant. The device is connected to the patient’s vascular system via an anastomosis graft bringing oxygen and nutrients to the transplanted cells of which oxygen is the limiting factor for long-term viability. Mathematically, we propose a (nolinear) fluid–poroelastic structure interaction model to describe the flow of blood plasma through the scaffold containing the cells, and a set of (nonlinear) advection–reaction–diffusion equations defined on moving domains to study oxygen supply to the cells. These macro-scale models are solved using finite element method based solvers. One of the novelties of this work is the design of a novel second-order accurate fluid–poroelastic structure interaction solver, for which we prove that it is unconditionally stable. At the micro/nano-scale, Smoothed Particle Hydrodynamics (SPH) simulations are used to capture the micro/nano-structure (architecture) of cell scaffolds and obtain macro-scale parameters, such as hydraulic conductivity/permeability, from the micro-scale scaffold-specific architecture. To avoid expensive micro-scale simulations based on SPH simulations for every new scaffold architecture, we use Encoder–Decoder Convolution Neural Networks. Based on our numerical simulations, we propose improvements in the current prototype design. For example, we show that highly elastic scaffolds have a higher capacity for oxygen transfer, which is an important finding considering that scaffold elasticity can be controlled during their fabrication, and that elastic scaffolds improve cell viability. The mathematical and computational approaches developed in this work provide a benchmark tool for computational analysis of not only iBAP, but also, more generally, of cell encapsulation strategies used in the design of devices for cell therapy and bio-artificial organs. 

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4. 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)

   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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5. 4D anisotropic skeletal muscle tissue constructs fabricated by staircase effect strategy

   https://doi.org/10.1088/1758-5090/ab1d07  

   Miao, Shida ; Nowicki, Margaret ; Cui, Haitao ; Lee, Se-Jun ; Zhou, Xuan ; Mills, David K ; Zhang, Lijie Grace ( January 2019 , Biofabrication)

   Like the morphology of native tissue fiber arrangement (such as skeletal muscle), unidirectional anisotropic scaffolds are highly desired as a means to guide cell behavior in anisotropic tissue engineering. In contrast, contour-like staircases exhibit directional topographical cues and are judged as an inevitable defect of fused deposition modeling (FDM). In this study, we will translate this staircase defect into an effective bioengineering strategy by integrating FDM with surface coating technique (FCT) to investigate the effect of topographical cues on regulating behaviors of human mesenchymal stem cells (hMSCs) toward skeletal muscle tissues. This integrated approach serves to fabricate shape-specific, multiple dimensional, anisotropic scaffolds using different biomaterials. 2D anisotropic scaffolds, first demonstrated with different polycaprolactone concentrations herein, efficiently direct hMSC alignment, especially when the scaffold is immobilized on a support ring. By surface coating the polymer solution inside FDM-printed sacrificial structures, 3D anisotropic scaffolds with thin wall features are developed and used to regulate seeded hMSCs through a self-established rotating bioreactor. Using layer-by-layer coating, along with a shape memory polymer, smart constructs exhibiting shape fix and recovery processes are prepared, bringing this study into the realm of 4D printing. Immunofluorescence staining and real-time quantitative polymerase chain reaction analysis confirm that the topographical cues created via FCT significantly enhance the expression of myogenic genes, including myoblast differentiation protein-1, desmin, and myosin heavy chain-2. We conclude that there are broad application potentials for this FCT strategy in tissue engineering as many tissues and organs, including skeletal muscle, possess highly organized and anisotropic extracellular matrix components. 

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