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1. Computational Fluid Dynamics Modeling of Material Transport Through Triply Periodic Minimal Surface Scaffolds for Bone Tissue Engineering

   https://doi.org/10.1115/1.4067575  

   Coburn, Brandon; Salary, Roozbeh “Ross” (March 2025, Journal of Biomechanical Engineering)

   Nguyen, Thao Vicky; Ethier, C Ross (Ed.)

   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: (i) to identify the consequential mechanisms behind internal and external material transport through/over porous bone scaffolds designed based on the principles of triply periodic minimal surfaces (TPMS) and (ii) to identify TPMS designs with optimal geometry and flow characteristics for the treatment of bone fractures in clinical practice. In this study, advanced CFD models were established based on ten TPMS scaffold designs for (i) single-unit internal flow analysis, (ii) single-unit external flow analysis, and (iii) cubic, full-scaffold external flow analysis, where the geometry of each design was parametrically created. The influence of several design parameters, such as surface representation iteration, wall thickness, and pore size on geometry accuracy as well as computation 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, according to the fundamentals of internal and external Newtonian flow modeling. The main fluid characteristics influential in bone regeneration, including flow velocity, flow pressure, and wall shear stress (WSS), were analyzed to observe material transport internally through and externally over the TPMS scaffold designs. Regarding the single-unit internal flow analysis, it was observed that P.W. Hybrid and Neovius designs had the highest level of not only flow pressure but also WSS. This can be attributed to their relatively flat surfaces when compared to the rest of the TPMS designs. Schwarz primitive (P) appeared to have the lowest level of flow pressure and WSS (desirable for development of bone tissues) due to its relatively open channels allowing for more effortless fluid transport. An analysis of streamline velocity exhibited an increase in velocity togther with a depiction of potential turbulent motion along the curved sections of the TPMS designs. Regarding the single-unit external flow analysis, it was observed that Neovius and Diamond yielded the highest level of flow pressure and WSS, respectively, while Schwarz primitive (P) similarly had a relatively low level of flow pressure and WSS suitable for bone regeneration. Besides, pressure buildup was observed within the inner channels of almost all the TPMS designs due to flow resistance and the intrinsic interaction between the fluid flow and the scaffold walls. Regarding the cubic (full-scaffold) external flow analysis, the Diamond and Schwarz gyroid (G) designs appeared to have a relatively high level of both flow pressure and WSS, while Schwarz primitive (P) similarly yielded a low level of flow pressure and WSS. 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. 

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2. Numerical Design, Fabrication, and Characterization of Porous Tissue Scaffolds for Bone Regeneration

   Coburn, Brandon (July 2024, Marshall Digital Scholar (https://mds.marshall.edu/etd/1910))

   With the recent advancements within biomedical engineering of bone tissue scaffolds, there is still a need to develop mechanically robust and biocompatible with low immunogenicity for bone regeneration. Additionally, the evaluation of the fluid dynamics of the porous Triply Periodic Minimal Surfaces (TPMS) bone scaffold also shows the need for investigation due to the complex fluid interaction of hemodynamics that occurs with the scaffold internal and external domains. To aid in the development of treating bone fractures, defects, and diseases. Furthermore, with the induction of a wide variety of TPMS architecture that yields different topologies, the Convolutional Neural Network (CNN) model will aid in predicting the TPMS scaffold characteristic to help develop critical design parameters. Thus, this research has observed biocompatible and mechanically strong materials with bone regeneration applications by evaluating polyamide, polyolefin, and cellulose fibers (PAPC) and SimuBone biomaterial. The TPMS scaffolds are fabricated by fused deposition modeling (FDM) additive manufacturing. Furthermore, the evaluation of fluid dynamics of internal and external effects using the computational fluid dynamics (CFD) method is used to observe the fluid interaction of the TPMS scaffold. Therefore, ANSYS (Fluent with Fluent Meshing) software captures the pressure, wall shear stress, and velocity streamline characteristics. As for the bone scaffold topology prediction, machine learning CNN is used and developed within Python to observe these properties. Accuracy, loss, validation accuracy, validation loss, and F-Score will be recorded to aid in developing the hyperparameters with the CNN platform. Therefore, the findings show that PAPC compression modulus performance observed that Neovius and Schwarz-Diamond designs have higher levels of compression strength than that of Schwarz-Primitive and Schwarz-Gyroid designs. As for SimuBone biomaterial, it was observed to be a suitable bone tissue engineering material due to its robust mechanical performance. Additionally, it is observed that the vertical orientations of P.W. Hybrid showed optimal performance with the compression analysis out of 10 different TPMS designs. It also has suitable mechanical mimicry of human trabecular bone yield strength. The evaluation of the CFD analysis of the internal and external performance of 10 TPMS scaffold designs showed that Schwarz Primitive yielded superior fluid properties. The wall shear stress was the lowest for analysis, with the external cubic evaluation showing Schwarz Primitive has a wall shear stress value of 3.4 mPa. In addition, its fluid pressure performance was suitable for improving cell viability and survival. Furthermore, the CNN evaluations displayed the optima hyperparameter for batch size, convolutional layers, dense layers, layer size, and Epoch training as 16, 6, 3, 32, and 25, respectively. A trend can be discerned within accuracy, loss, validation accuracy, validation loss, and F-Score performance, all yielding improved and consistent performance with the 5-replication analysis. Thus, this research has observed the fluid dynamics, mechanical performance, and topology evaluation of the TPMS bone scaffold. This study will aid in designing and experimenting with bone tissue engineering scaffold development. 

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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. Mechanical Characterization of Porous Bone-like Scaffolds with Complex Microstructures for Bone Regeneration

   https://doi.org/10.3390/bioengineering12040416  

   Coburn, Brandon; Salary, Roozbeh Ross (April 2025, Bioengineering)

   Janorkar, Amol V; Vozzi, Giovanni (Ed.)

   The patient-specific treatment of bone fractures using porous osteoconductive scaffolds has faced significant clinical challenges due to insufficient mechanical strength and bioactivity. These properties are essential for osteogenesis, bone bridging, and bone regeneration. Therefore, it is crucial to develop and characterize biocompatible, biodegradable, and mechanically robust scaffolds for effective bone regeneration. The objective of this study is to systematically investigate the mechanical performance of SimuBone, a medical-grade biocompatible and biodegradable material, using 10 distinct triply periodic minimal surface (TPMS) designs with various internal structures. To assess the material’s tensile properties, tensile structures based on ASTM D638-14 (Design IV) were fabricated, while standard torsion structures were designed and fabricated to evaluate torsional properties. Additionally, this work examined the compressive properties of the 10 TPMS scaffold designs, parametrically designed in the Rhinoceros 3D environment and subsequently fabricated using fused deposition modeling (FDM) additive manufacturing. The FDM fabrication process utilized a microcapillary nozzle (heated to 240 °C) with a diameter of 400 µm and a print speed of 10 mm/s, depositing material on a heated surface maintained at 60 °C. It was observed that SimuBone had a shear modulus of 714.79 ± 11.97 MPa as well as an average yield strength of 44 ± 1.31 MPa. Scaffolds fabricated with horizontal material deposition exhibited the highest tensile modulus (5404.20 ± 192.30 MPa), making them ideal for load-bearing applications. Also, scaffolds with large voids required thicker walls to prevent collapse. The P.W. Hybrid scaffold design demonstrated high vertical stiffness but moderate horizontal stiffness, indicating anisotropic mechanical behavior. The Neovius scaffold design balanced mechanical stiffness and porosity, making it a promising candidate for bone tissue engineering. Overall, the outcomes of this study pave the way for the design and fabrication of scaffolds with optimal properties for the treatment of bone fractures. 

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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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