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International Journal of Bioprinting                              Design and optimization of 3DP bioscaffolds




            2.3.2. Oxygen transport process                       where  R   is  the  oxygen  consumption  rate;  C   is  the
                                                                                                       2
                                                                         0
            Oxygen serves as the sole substrate for cell growth. As   oxygen concentration in the porous domain; Vo max  is the
            the flow velocity within the system changes, the oxygen   maximum oxygen absorption rate by the cells; K  denotes
                                                                                                      m
            transport transitions from a single diffusion to a coupled   the oxygen concentration value at which the absorption
            convection–diffusion process. The oxygen diffusion–  rate reaches half of its maximum; and ρ  is the cell density.
                                                                                              c
            convection process in region Ω  is governed by Equation   Additionally, it is necessary to consider  the adaptation
                                     1
            12:                                                process, cell spreading, and deformation within the
                                                               scaffold. In this model, it is assumed that Vo max  increases
                      ∂C                                       from zero at the beginning to a maximum value at a certain
                        1  =∇⋅DC t()  −v  ⋅∇Ct()     (12)
                                ∇
                              
                                     
                       ∂t         1      1   1                 time, as expressed in Equation 18:
               where C  represents the dissolved oxygen concentration              Vt ⋅ r  (0≤<
                                                                                  
                                                                                           tt )
                     1
            in Ω , and D indicates the diffusion coefficient of oxygen in      V o max    3  1           (18)
               1
            the nutrient solution. This equation describes the oxygen               V r  ( 1 ≤
                                                                                          tt)
            concentration  changes  due  to  the  combined  effects  of
            spontaneous oxygen diffusion (the first term on the right-  where  Vo max  represents the actual maximum oxygen
            hand side) and convection caused by fluid flow (the second   absorption rate, and t  is the nodal time.
                                                                                1
            term on the right-hand side). Under different spatial and   2.3.4. Cell growth kinetics
            temporal conditions, C  should satisfy the corresponding   After oxygen consumption, cell proliferation and division
                              1
            boundary conditions as in Equation 13:             occur. The cell growth kinetics described by the first-order
                                                               growth  process  is  simulated  by  utilizing  the  modified
                             C = c xy zt(, ,, )        (13)    Contois model, as expressed in Equation 19:
                                 1
                              1
               In the porous medium region Ω  of the scaffold, the                  µ    ⋅ Ct()
                                          2
                                                                                           2
            oxygen transport should satisfy Equation 14:                 µ t() =  K c  ρ ⋅  m  cmax ⋅ ρ t()+ C t()  (19)
                                                                          c
                                                                                      V ⋅
                                                                                       c
                                                                                                2
                                                                                          c
                ∂Ct ()
                   2  =∇⋅Dt () ∇Ct ()  −v  ⋅∇C t () − R t()   (14)  where µ  indicates the specific growth rate of cells; µ
                          
                                     
                                                                                                           cmax
                  ∂t        e     2     B    2    0            denotes the maximum specific growth rate of cells during
                                                                        c
                                                               the growth process; C is the oxygen concentration within
               where C expresses the oxygen concentration within the            2
                     2
            biological scaffold; D  is the effective diffusion coefficient   the porous medium domain; K is the Contois parameter;
                                                                                        c
                                                               ρ  represents the mass density of cells; V is the volume of
                             e
            of oxygen within the scaffold; and R  denotes the oxygen   an individual cell; and ρ  represents the density of cells. The
                                                                                                c
                                                                m
                                         0
            consumption rate by cells. C  should satisfy Equation 15   change in cell density can be expressed using the Contois
                                                                                  c
                                   2
            within the region.
                                                               equation as follows:
                            C = c xy zt(, ,, )         (15)
                                 2
                              2
                                                                              ∂ρ t()  = µ t() ⋅ ρ t ()    (20)
                                                                                c
               The effective diffusion coefficient of oxygen D  varies         ∂t     c    c
                                                    e
            due to changes in porosity caused by cell growth, and this
            process satisfies Equation 16.                        In reality, the growth process of cells in the scaffold
                                                               should consider an initial phase lag due to cell adhesion and
                                                               spreading. Therefore, a step-wise profile for the maximum
                               D =  ε t ()  ⋅ D        (16)    specific growth rate µ   is necessary in the model:
                                e
                                  Γ  t ()                                       cmax
            2.3.3. Oxygen consumption process                                 0        ( 0 t  t )
                                                                                          ≤<
            Oxygen enters the scaffold (region Ω ) and is then absorbed    µ ⋅− )             0
                                                                              (
                                                                               tt
                                                                          
                                        2
                                                                                            t
                                                                                               t
                                                                                  0
                                                                            r
            and consumed by the cells. The cell oxygen consumption          t − t      ( t ≤< )          (21)
                                                                                               1
                                                                                         0
            term in Equation 14 is calculated by the Michaelis–Menten        1 µ  0      ( t < t)
                                                                          
                                                                                           1
            equation (Equation 17).                                            r
                               Vo   Ct()                          where µ  represents the actual input of the maximum
                                                                        r
                                  max
                                     2
                         Rt() =  K +  C t() ρ c  t ()  (17)    specific growth rate in the model, and t represents time. t 0
                          0
                                     2
                                 m
                                                               is the cell adhesion time, while t  indicates the spreading
                                                                                         1
            Volume 10 Issue 3 (2024)                       281                                doi: 10.36922/ijb.1838
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