skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: High-Fidelity Simulation of Flows in Bone-Like Environment to Investigate the Growth of Cancer Cells
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.  more » « less
Award ID(s):
1946202
PAR ID:
10318358
Author(s) / Creator(s):
; ; ; ;
Date Published:
Journal Name:
2021 Design of Medical Devices Conference
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. 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
  2. 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
  3. 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
  4. Abstract Incurable breast cancer bone metastasis causes widespread bone loss, resulting in fragility, pain, increased fracture risk, and ultimately increased patient mortality. Increased mechanical signals in the skeleton are anabolic and protect against bone loss, and they may also do so during osteolytic bone metastasis. Skeletal mechanical signals include interdependent tissue deformations and interstitial fluid flow, but how metastatic tumor cells respond to each of these individual signals remains underinvestigated, a barrier to translation to the clinic. To delineate their respective roles, we report computed estimates of the internal mechanical field of a bone mimetic scaffold undergoing combinations of high and low compression and perfusion using multiphysics simulations. Simulations were conducted in advance of multimodal loading bioreactor experiments with bone metastatic breast cancer cells to ensure that mechanical stimuli occurring internally were physiological and anabolic. Our results show that mechanical stimuli throughout the scaffold were within the anabolic range of bone cells in all loading configurations, were homogenously distributed throughout, and that combined high magnitude compression and perfusion synergized to produce the largest wall shear stresses within the scaffold. These simulations, when combined with experiments, will shed light on how increased mechanical loading in the skeleton may confer anti‐tumorigenic effects during metastasis. 
    more » « less
  5. Abstract Prostate cancer bone metastasis is the leading cause of cancer-related mortality in men in the United States, causing severe damage to skeletal tissue. The treatment of advanced-stage prostate cancer is always challenging due to limited drug treatment options, resulting in low survival rates. There is a scarcity of knowledge regarding the mechanisms associated with the effects of biomechanical cues by the interstitial fluid flow on prostate cancer cell growth and migration. We have designed a novel bioreactor system to demonstrate the impact of interstitial fluid flow on the migration of prostate cancer cells to the bone during extravasation. First, we demonstrated that a high flow rate induces apoptosis in PC3 cells via TGF-β1 mediated signaling; thus, physiological flow rate conditions are optimum for cell growth. Next, to understand the role of interstitial fluid flow in prostate cancer migration, we evaluated the migration rate of cells under static and dynamic conditions in the presence or absence of bone. We report that CXCR4 levels were not significantly changed under static and dynamic conditions, indicating that CXCR4 activation in PC3 cells is not influenced by flow conditions but by the bone, where CXCR4 levels were upregulated. The bone-upregulated CXCR4 levels led to increased MMP-9 levels resulting in a high migration rate in the presence of bone. In addition, upregulated levels ofαvβ3integrins under fluid flow conditions contributed to an overall increase in the migration rate of PC3 cells. Overall, this study demonstrates the potential role of interstitial fluid flow in prostate cancer invasion. Understanding the critical role of interstitial fluid flow in promoting prostate cancer cell progression will enhance current therapies for advanced-stage prostate cancer and provide improved treatment options for patients. 
    more » « less