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International Journal of Bioprinting                              Design and optimization of 3DP bioscaffolds




            analyze and simulate light-cured 3D-bioprinted scaffolds   •  The entire system is assumed to contain sufficient
            under dynamic in vitro cultivation conditions. The model   nutrients, considering only oxygen as the sole
            was validated by comparing the predicted results with     substrate for cell metabolism and growth.
            those observed in experiments of C2C12 cell culture,    •  Oxygen molecules are considered to be uniformly
            demonstrating high capability  in modeling  cell growth   dissolved in the nutrient solution at a specific
            behaviors. Utilizing this multi-physics model, parametric   concentration.
            scanning simulations of nutrient flow rate were conducted
            to determine appropriate wall shear stress levels that   •  The system environment is maintained at 37°C
            promote  C2C12  cell  growth.  Furthermore,  the  impact   and 5% carbon dioxide, an optimal condition for
            of different dynamic parameters, such as inlet flow rate,   cell survival.
            geometric feature size, and initial cell density, on scaffold-  •  The maximum absorption rate of oxygen by cells
            based tissue engineering outcomes was examined. Lastly,
            based on the modeling system proposed in this study, a    linearly increases from zero until a certain time
            two-step optimization strategy is proposed for structural   point, where it remains constant.
            optimization of scaffolds and applied for designing     •  The cells within the scaffold experience an initial
            channeled scaffold with maximum cell proliferation.       adhesion phase for the first 3 hours of cultivation,
            This strategy offers a novel framework for designing      during which their maximum growth rate is zero,
            and optimizing multi-channel  bioprinted  scaffolds       followed by linear growth until a certain time
            encapsulated with cells for advanced tissue engineering.  point where it remains constant.

            2. Model physics and implementation                     •  The influence of cell death is not considered in
                                                                      the model.
            2.1. Model assumptions
            The multi-physics coupling model for cell growth        •  The effects of material swelling are ignored.
            considers fluid convection, oxygen mass transfer, cellular   2.2. Computational domain
            oxygen consumption, and cell growth involved in the   In the geometric assembly of the multi-physics model, as
            dynamic cultivation process of DLP 3D-printed scaffolds.   shown in Figure 1a, the entire geometric space is divided
            In practice, the physical processes involved in the entire   into two domains: Ω  representing the uniform medium
                                                                                1
            cultivation process are more complex. To reduce the   flow region of the nutrient solution, and Ω  expressing the
                                                                                                 2
            complexities of the modeling process while maintaining   porous medium flow region of the scaffold. The scaffold
            satisfactory prediction results, the following assumptions   structure in the model is a circular block with a diameter
            are made:                                          of 4 mm and a thickness of 2 mm. The chamber is a hollow
                 •  The pores within the scaffold are assumed to be   cylindrical structure with an inner diameter D  of 5 mm
                                                                                                     1
                   uniformly distributed.                      and a total length L of 10 mm. The scaffold is placed at the






















            Figure 1. Geometric assembly of the scaffold in dynamic in vitro cultivation and physical processes of cell growth to be modeled. (a) Schematic diagram
            showing the geometry of the computational domain for model simulation. Ω  represents the homogeneous medium flow region of the nutrient solution,
                                                             1
            and Ω  is the porous medium flow region of the scaffold. (b) Physical processes incorporated in the model, including fluid convection occurred in domain
                2
            Ω and Ω , oxygen diffusion in the scaffold, oxygen consumption by cells, and cell growth.
             1    2
            Volume 10 Issue 3 (2024)                       279                                doi: 10.36922/ijb.1838
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