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16.5 IMPLEMENTATION 321
16.4.2.3 Source Terms and Diffusion for Chemical Species
Source terms in Eq. (16.4) include production and consumption of species. The net production/consumption of the ith
chemical species by the jth cell phenotype can be modeled using an equation of the kind:
F ¼F ðC 1 ,…,C n ,S 1 ,…,S m ,θÞ, i ¼ 1,…,m, j ¼ 1,…,n (16.24)
0
0
ij ij
16.4.2.3.1 DIFFUSION
As for cellular phenotypes, diffusion is stated as
q ¼ K 0 —S i , i ¼ 1,…,m (16.25)
0
i D,i
Here, matrix K 0 D,i is the diffusion matrix that will be expressed as
K 0 0 ðC 1 ,…,C n ,θ,p 1 ,…,p k Þ, i ¼ 1,…,m (16.26)
D,i ¼K D,i
16.4.3 ECM Remodeling Coupling
One last step in this global framework corresponds to regeneration considerations. Mechanical parameters of the sub-
strate p 1 , …, p k can be seen as constant parameters, such as elastic parameters (Young modulus E, Poisson coefficient ν,
etc.), or may be thought of as evolving parameters. In this latter approach, a dynamic approach to the problem is
adopted, being necessary to define an evolution relationship:
_ p ¼R i ðC 1 ,…,C n ,θÞ, i ¼ 1,…,k (16.27)
i
16.5 IMPLEMENTATION
16.5.1 3D Finite Element Implementation
16.5.1.1 Weak Form
1 1 1
0
0
The weak form of Eqs. (16.1), (16.4) is derived. Let ϕ 2H ðΩÞ, i ¼ 1, …, n, j ¼ 1, …, m, being H ðΩÞ the closure in H ðΩÞ
1
2
(H ðΩÞ¼ W 1,2 ðΩÞ), with this latter, the Sobolev space with respect to the L norm of differentiable functions (in the
weak sense) of order 1 of infinitely differentiable functions compactly supported in Ω or equivalently, the space of
1
functions in H ðΩÞ that vanish at the boundary ∂Ω.
1
Eq. (16.1) can be multiplied by a test function ϕ 2H ðΩÞ and integrated in Ω to obtain
0
Z Z
ϕ ∂C i + ϕ— A i dΩ ¼ a i ϕdΩ, i ¼ 1,…,n (16.28)
Ω ∂t Ω
where we have defined
A i ¼ C i v + q
i
n
X
a i ¼ C i F i + ðC j F ji C i F ij Þ
j ¼ 1
j 6¼ i
where, respectively, Dirichlet or Robin-
Integrating by parts Eq. (16.28), splitting the boundary ∂Ω ¼ Γ D i [Γ R i
Neumann boundary conditions are applied, and using that ϕ vanishes at the boundary, results in:
Z Z Z
∂C i ∂C i
ϕ —ϕ A i dΩ ¼ ϕa i dΩ ϕ dΓ, i ¼ 1,…,n (16.29)
Ω ∂t Ω Γ R i ∂n
we arrive to
Multiplying Eq. (16.2) by a test function ϕ and integrating in Γ D i
Z Z
ϕf i dΓ, i ¼ 1,…,n
ϕC i dΓ ¼ (16.30)
Γ D i Γ D i
II. MECHANOBIOLOGY AND TISSUE REGENERATION