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Introduction
Biomaterial matrices for drug release are useful for in vivo tissue regeneration. The
following example describes the release of a drug from a biomaterial matrix to damaged
cell tissue. Specifically, a nerve guide delivers a regenerating drug to damaged nerve ends.
This application examines detailed drug-release kinetics with rate expressions handling
drug dissociation/association reactions as well as matrix degradation by enzyme catalysis.
The enzyme reaction is described by Michaelis-Menten kinetics. The model enables
investigation of design parameters governing the rate of drug release such as drug-to-
biomaterial affinity, biomaterial degradation, drug loading, and the influence of geometry
and composition of the biomaterial matrix.
Model Definition
The model consists of two parts. One part uses the batch reactor type in the Reaction
Engineering interface to specify the reacting system in a perfectly mixed environment, that
is, no space dependency is assumed. The purpose of this part is to study the reaction
kinetics. The other part is space dependent and is generated from the Reaction
Engineering interface. It utilizes the Transport of Diluted Species interface and serves to
investigate the drug transport into a region containing damaged nerve ends.
Figure 1 shows the full 3D geometry as well as the 2D modeling domain, reduced by axial
symmetry and a mirror plane, for the space-dependent model. The biomaterial holding the
drug is assumed to have a strictly cylindrical shape. The three distinct areas (domains) are:
Biomaterial tissue
Surroundings
Figure 1: The full 3D geometry (left) and the equivalent modeling domains reduced to 2D by
axial symmetry (right). The regions are: the nerve-cell tissue, the biomaterial matrix, and the
surrounding medium.
Two mechanisms release the drug from the matrix. First, the drug can simply dissociate
from the matrix site mp. Second, matrix degradation by an enzyme, e, originating from
the cell-tissue domain, leads to release of the drug-peptide species, pd, from which the
drug subsequently dissociates. The unbound species p, d, pd, and e are active in the entire
model domain. Figure 2 illustrates the complete reaction scheme.
f d
k1
d + p p
m k1r m
f f
k2r k2 k2r k2
Degradation
E pE pE E
m m
f f
k3 k3
d
d + p f p
k1
m k1r m
∂c i
------- + ∇ ⋅ ( – D ik ∇c i ) = R ik (1)
∂t
where Dik (SI unit: m2/s) is the diffusion coefficient for species i in the respective
medium. Further, Rik (SI unit: mol/(m3·s)) is the rate expression for species i in the
medium. In the matrix, all the reactions described in Figure 2 are possible, leading to the
f r
R d2 = – k 1 c d ( c mp + c p ) + k 1 ( c mpd + c pd )
f r
R p2 = – k 1 c d c p + k 1 c pd + R MMmp
f r
R pd2 = k 1 c d c p – k 1 c pd + R MMmpd
f r
R mp2 = – k 1 c d c mp + k 1 c mpd – R MMmp
f r
R mpd2 = k 1 c d c mp – k 1 c mpd – R MMmpd
The rate terms RMMmp and RMMmpd refer to the Michaelis-Menten kinetics describing
the enzyme catalyzed degradation of the matrix:
V max c mp
R MMmp = ------------------------
K M + c mp
V max c mpd
R MMmpd = ---------------------------
K M + c mpd
with
f
V max = k 3 c e
f r
k3 + k2
KM = -----------------
f
-
k2
RMMmp describes the disappearance of mp sites and the production of p species. RMMmpd
describes the disappearance of mpd sites and the production of pd species. Vmax is the
maximum rate and KM the Michaelis-Menten constant. In the cell region and in the
surrounding medium only dissociation/association reactions occur, leading to the rate
expressions
f r
R d1 = R d3 = R p1 = R p3 = – k 1 c d c p + k 1 c pd
f r
R pd1 = R pd3 = k 1 c d c p – k 1 c pd
Figure 3: Concentrations of all reacting species (mol/ m3) as functions of time (s).
The effect of enzyme degradation is clearly visible, with matrix-bound peptide species (mp
and mpd) decreasing and free peptide species (p and pd) increasing with time. The matrix
is completely degraded after approximately 5000 seconds. As the drug and peptide species
have the same association/dissociation kinetics, no matter the peptide is free or matrix-
bound, the steady-state concentration of drug is constant during the degradation process.
Figure 5: Concentration profiles describing the total drug concentration (cd + cpd) across the
modeling domain. Profiles were collected at times up to 6000 s.
Figure 6: Concentration profiles describing the total matrix site concentration (cmp + cmpd)
with profiles collected at times up to 6000 s.
The detailed reaction/transport description in this model allows for the investigation of
many design parameters relevant to bioengineering. This case presents the effect of matrix
degradation on drug release as a function of time and geometry. Furthermore, it is
straightforward to study the influence of the drug/peptide affinity by varying the rate
constants kf1 and kr1, or the influence of drug loading by varying the cmp : cmpd ratio. Of
course, the ability to examine alternative geometries and mixed biomaterial domains gives
even more design flexibility.
Reference
1. D.J. Maxwell, B.C. Hicks, S. Parsons, and S.E. Sakiyama-Elbert, “Development of
rationally designed affinity-based drug delivery systems”, Acta Biomat., vol. 1, no. 1, pp.
101–113, 2005.
Modeling Instructions
From the File menu, choose New.
NEW
In the New window, click Model Wizard.
MODEL WIZARD
1 In the Model Wizard window, click 0D.
2 In the Select Physics tree, select Chemical Species Transport>Reaction Engineering (re).
3 Click Add.
4 Click Study.
5 In the Select Study tree, select Preset Studies>Time Dependent.
6 Click Done.
GLOBAL DEFINITIONS
Read global parameters from a text file.
Parameters
1 In the Model Builder window, under Global Definitions click Parameters.
2 In the Settings window for Parameters, locate the Parameters section.
3 Click Load from File.
4 Browse to the model’s Application Libraries folder and double-click the file
drug_release_parameters.txt.
1 In the Model Builder window, under Component 1 (comp1) click Reaction Engineering (re).
2 In the Settings window for Reaction Engineering, click to expand the Mixture properties
section.
Reaction 1
1 On the Reaction Engineering toolbar, click Reaction.
2 In the Settings window for Reaction, locate the Reaction Formula section.
3 In the Formula text field, type d+mp<=>mpd.
4 Click Apply.
5 Locate the Rate Constants section. In the kf text field, type kf_d.
6 In the kr text field, type kr_d.
Reaction 2
1 On the Reaction Engineering toolbar, click Reaction.
2 In the Settings window for Reaction, locate the Reaction Formula section.
3 In the Formula text field, type d+p<=>pd.
4 Click Apply.
5 Locate the Rate Constants section. In the kf text field, type kf_d.
6 In the kr text field, type kr_d.
Species 1
1 On the Reaction Engineering toolbar, click Species.
2 In the Settings window for Species, locate the Species Name section.
3 In the Species name text field, type e.
4 On the Reaction Engineering toolbar, click Species.
5 In the Settings window for Species, locate the Species Name section.
6 In the Species name text field, type h2o.
7 Locate the Species Type section. From the Species type list, choose Solvent.
Initial Values 1
1 In the Model Builder window, under Component 1 (comp1)>Reaction Engineering (re)
click Initial Values 1.
2 In the Settings window for Initial Values, locate the Volumetric Species Initial Value
section.
Additional Source 1
Add additional Michaelis-Menten reaction rates for species p, pd, mp and mpd.
STUDY 1
RESULTS
Concentration (re)
Follow these steps to create Figure 3.
Global 1
1 In the Model Builder window, expand the Results>
Concentration within biomatrix material, OD model node, then click Global 1.
2 In the Settings window for Global, click to expand the Title section.
3 From the Title type list, choose None.
4 Click to expand the Coloring and style section. Locate the Coloring and Style section. In
the Width text field, type 2.
5 Click to expand the Legends section. From the Legends list, choose Manual.
6 In the table, enter the following settings:
Legends
Drug
Matrix-bound peptide
Matrix-bound drug-peptide
Peptide
Drug-peptide
Enzyme
Start setting up the space-dependent model by exporting the settings of the Reaction
Engineering interface with the Generate Space-Dependent Model feature.
GEOMETRY 1(2DAXI)
1 In the Model Builder window, expand the Component 2 (comp2) node, then click
Geometry 1(2Daxi).
2 In the Settings window for Geometry, locate the Units section.
3 From the Length unit list, choose mm.
Rectangle 1 (r1)
1 On the Geometry toolbar, click Primitives and choose Rectangle.
2 In the Settings window for Rectangle, locate the Size and Shape section.
3 In the Width text field, type 6.
4 In the Height text field, type 9.
Rectangle 2 (r2)
1 On the Geometry toolbar, click Primitives and choose Rectangle.
2 In the Settings window for Rectangle, locate the Size and Shape section.
3 In the Height text field, type 9.
Rectangle 3 (r3)
1 On the Geometry toolbar, click Primitives and choose Rectangle.
2 In the Settings window for Rectangle, locate the Size and Shape section.
3 In the Width text field, type 2.
4 In the Height text field, type 6.
5 Locate the Position section. In the r text field, type 1.
6 Right-click Rectangle 3 (r3) and choose Build Selected.
DEFINITIONS
Explicit 1
1 On the Definitions toolbar, click Explicit.
2 In the Settings window for Explicit, type Biomaterial matrix in the Label text field.
3 Select Domain 2 only.
Explicit 2
1 On the Definitions toolbar, click Explicit.
2 In the Settings window for Explicit, type Nerve cell tissue in the Label text field.
Explicit 3
1 On the Definitions toolbar, click Explicit.
2 In the Settings window for Explicit, type Surroundings in the Label text field.
3 Select Domain 3 only.
Explicit 4
1 On the Definitions toolbar, click Explicit.
2 In the Settings window for Explicit, type Nerve and surroundings in the Label text
field.
3 Select Domains 1 and 3 only.
The automatically generated Chemistry interface is based on the conditions for the
biomaterial matrix.
CHEMISTRY 1 (CHEM)
1 In the Model Builder window, under Component 2 (comp2) click Chemistry 1 (chem).
2 In the Settings window for Chemistry, type Chemistry - Biomaterial matrix in the
Label text field.
3 Locate the Model Inputs section. In the T text field, type T_in.
COMPONENT 2 (COMP2)
Add a new Chemistry interface for the drug dissociation taking place in the nerve cell tissue
and surroundings.
ADD PHYSICS
1 On the Home toolbar, click Add Physics to open the Add Physics window.
2 Go to the Add Physics window.
3 In the tree, select Chemical Species Transport>Chemistry (chem).
4 Click Add to Component in the window toolbar.
5 On the Home toolbar, click Add Physics to close the Add Physics window.
CHEMISTRY 2 (CHEM2)
1 In the Settings window for Chemistry, type Chemistry - Nerve and Surroundings
in the Label text field.
2 Locate the Model Inputs section. In the T text field, type T_in.
Reaction 1
1 On the Physics toolbar, click Domains and choose Reaction.
2 In the Settings window for Reaction, locate the Reaction Formula section.
3 In the Formula text field, type D+P<=>PD.
4 Click Apply.
5 Locate the Rate Constants section. In the kf text field, type kf_d.
6 In the kr text field, type kr_d.
Species 1
1 On the Physics toolbar, click Domains and choose Species.
2 In the Settings window for Species, locate the Species Name section.
3 In the Species name text field, type E.
4 On the Physics toolbar, click Domains and choose Species.
5 In the Settings window for Species, locate the Species Name section.
6 In the Species name text field, type H2O.
7 Locate the Species Type section. From the Species type list, choose Solvent.
8 In the Model Builder window, click Chemistry - Nerve and Surroundings (chem2).
9 In the Settings window for Chemistry, locate the Species Matching section.
10 In the table, enter the following settings:
With the molar masses added it is possible to compute several transport properties outside
the scope of this example.
Species: mp
1 In the Model Builder window, under Component 2 (comp2)>Chemistry -
Biomaterial matrix (chem) click Species: mp.
2 In the Settings window for Species, locate the General Parameters section.
3 In the M text field, type Mnp.
Species: mpd
1 In the Model Builder window, under Component 2 (comp2)>Chemistry -
Biomaterial matrix (chem) click Species: mpd.
2 In the Settings window for Species, locate the General Parameters section.
3 In the M text field, type Mnpd.
Species: p
1 In the Model Builder window, under Component 2 (comp2)>Chemistry -
Biomaterial matrix (chem) click Species: p.
2 In the Settings window for Species, locate the General Parameters section.
3 In the M text field, type Mnp.
Species: pd
1 In the Model Builder window, under Component 2 (comp2)>Chemistry -
Biomaterial matrix (chem) click Species: pd.
2 In the Settings window for Species, locate the General Parameters section.
3 In the M text field, type Mnpd.
Species: e
1 In the Model Builder window, under Component 2 (comp2)>Chemistry -
Biomaterial matrix (chem) click Species: e.
2 In the Settings window for Species, locate the General Parameters section.
3 In the M text field, type Mne.
Species: D
1 In the Model Builder window, under Component 2 (comp2)>Chemistry -
Nerve and Surroundings (chem2) click Species: D.
2 In the Settings window for Species, locate the General Parameters section.
3 In the M text field, type Mnd.
Species: P
1 In the Model Builder window, under Component 2 (comp2)>Chemistry -
Nerve and Surroundings (chem2) click Species: P.
2 In the Settings window for Species, locate the General Parameters section.
3 In the M text field, type Mnp.
Species: PD
1 In the Model Builder window, under Component 2 (comp2)>Chemistry -
Nerve and Surroundings (chem2) click Species: PD.
2 In the Settings window for Species, locate the General Parameters section.
3 In the M text field, type Mnpd.
Species: E
1 In the Model Builder window, under Component 2 (comp2)>Chemistry -
Nerve and Surroundings (chem2) click Species: E.
2 In the Settings window for Species, locate the General Parameters section.
3 In the M text field, type Mne.
Species: H2O
1 In the Model Builder window, under Component 2 (comp2)>Chemistry -
Nerve and Surroundings (chem2) click Species: H2O.
2 In the Settings window for Species, locate the General Parameters section.
Continue setting the mass transport properties in the biomaterial matrix in the Transport
of Diluted Species interface.
TR A N S P O R T O F D I L U T E D S P E C I E S ( T D S )
On the Physics toolbar, click Chemistry - Nerve and Surroundings (chem2) and choose
Transport of Diluted Species (tds).
3 Locate the Domain Selection section. From the Selection list, choose Biomaterial matrix.
4 Locate the Transport Mechanisms section. Clear the Convection check box.
TR A N S P O R T O F D I L U T E D S P E C I E S - B I O M A T E R I A L M A T R I X ( T D S )
On the Physics toolbar, click Transport of Diluted Species (tds) and choose
Transport of Diluted Species - Biomaterial matrix (tds).
Transport Properties 1
1 In the Model Builder window, expand the Component 2 (comp2)>
Transport of Diluted Species - Biomaterial matrix (tds) node, then click
Transport Properties 1.
2 In the Settings window for Transport Properties, locate the Diffusion section.
3 In the Dcd text field, type Dd.
4 In the Dcmp text field, type Dmp.
5 In the Dcmpd text field, type Dmpd.
6 In the Dcp text field, type Dp.
7 In the Dcpd text field, type Dpd.
8 In the Dce text field, type De.
Initial Values 1
1 In the Model Builder window, under Component 2 (comp2)>Transport of Diluted Species -
Biomaterial matrix (tds) click Initial Values 1.
2 In the Settings window for Initial Values, locate the Initial Values section.
3 In the ce text field, type 0.
4 In the Model Builder window, click Transport of Diluted Species - Biomaterial matrix (tds).
ADD PHYSICS
1 On the Physics toolbar, click Add Physics to open the Add Physics window.
2 Go to the Add Physics window.
3 In the tree, select Chemical Species Transport>Transport of Diluted Species (tds).
4 Click Add to Component in the window toolbar.
5 On the Physics toolbar, click Add Physics to close the Add Physics window.
In the second Transport of Diluted Species interface the mass transport within the cell nerve
tissue and surroundings is set up.
TR A N S P O R T O F D I L U T E D S P E C I E S 2 ( T D S 2 )
1 In the Settings window for Transport of Diluted Species, type Transport of Diluted
Species - Nerve and Surroundings in the Label text field.
2 Locate the Domain Selection section. From the Selection list, choose
Nerve and surroundings.
3 Locate the Transport Mechanisms section. Clear the Convection check box.
4 Click to expand the Dependent variables section. Locate the Dependent Variables section.
In the Number of species text field, type 4.
cD
cP
cPD
cE
TR A N S P O R T O F D I L U T E D S P E C I E S - N E R VE A N D S U R R O U N D I N G S ( T D S 2 )
Transport Properties 1
1 In the Model Builder window, under Component 2 (comp2)>Transport of Diluted Species -
Nerve and Surroundings (tds2) click Transport Properties 1.
2 In the Settings window for Transport Properties, locate the Diffusion section.
3 In the DcD text field, type DsD.
4 In the DcE text field, type DsE.
5 In the DcP text field, type DsP.
6 In the DcPD text field, type DsPD.
Reactions 1
1 On the Physics toolbar, click Domains and choose Reactions.
2 In the Settings window for Reactions, locate the Domain Selection section.
3 From the Selection list, choose Nerve and surroundings.
4 Locate the Reaction Rates section. From the RcD list, choose
Rate expression for species D (chem2).
5 From the RcP list, choose Rate expression for species P (chem2).
6 From the RcPD list, choose Rate expression for species PD (chem2).
7 From the RcE list, choose Rate expression for species E (chem2/E).
Transport Properties 2
1 On the Physics toolbar, click Domains and choose Transport Properties.
2 In the Settings window for Transport Properties, type Transport Properties - Nerve
in the Label text field.
3 Locate the Domain Selection section. From the Selection list, choose Nerve cell tissue.
4 Locate the Diffusion section. In the DcD text field, type DnD.
5 In the DcE text field, type DnE.
6 In the DcP text field, type DnP.
Initial Values 2
1 On the Physics toolbar, click Domains and choose Initial Values.
2 In the Settings window for Initial Values, type Initial Values 2 - Nerve in the Label
text field.
3 Locate the Domain Selection section. From the Selection list, choose Nerve cell tissue.
4 Locate the Initial Values section. In the cE text field, type cnE_init.
MESH 1
Size
1 In the Model Builder window, under Component 2 (comp2) right-click Mesh 1 and choose
Size.
2 In the Settings window for Size, locate the Element Size section.
3 From the Predefined list, choose Extra fine.
Size 1
1 In the Model Builder window, under Component 2 (comp2)>Mesh 1 click Size 1.
2 In the Settings window for Size, locate the Geometric Entity Selection section.
3 From the Geometric entity level list, choose Boundary.
4 Click Paste Selection.
5 In the Paste Selection dialog box, type 4,7,9 in the Selection text field.
6 Click OK.
7 In the Settings window for Size, locate the Element Size section.
8 Click the Custom button.
9 Locate the Element Size Parameters section. Select the Maximum element size check box.
10 In the associated text field, type 0.1.
DEFINITIONS
Load the common concentration variables in domain 2 from a text file.
Variables 1
1 In the Model Builder window, under Component 2 (comp2) right-click Definitions and
choose Variables.
2 In the Settings window for Variables, type Variables - Biomaterial matrix in the
Label text field.
3 Locate the Geometric Entity Selection section. From the Geometric entity level list,
choose Domain.
4 Select Domain 2 only.
5 Locate the Variables section. Click Load from File.
6 Browse to the model’s Application Libraries folder and double-click the file
drug_release_variables1.txt.
Variables 2
1 In the Model Builder window, right-click Definitions and choose Variables.
Load the common concentration variables in domain 1 and 3 from a text file.
2 In the Settings window for Variables, type Variables - Nerve and surroundings in
the Label text field.
3 Locate the Geometric Entity Selection section. From the Geometric entity level list,
choose Domain.
4 Select Domains 1 and 3 only.
5 Locate the Variables section. Click Load from File.
6 Browse to the model’s Application Libraries folder and double-click the file
drug_release_variables2.txt.
STUDY 2
RESULTS
Concentration (tds) 1
1 In the Model Builder window, expand the Results>Data Sets node, then click Results>
Concentration (tds) 1.
2 In the Settings window for 3D Plot Group, type Concentration distribution drug
in the Label text field.
3 Locate the Data section. From the Data set list, choose Revolution 2D 1.
4 From the Time (s) list, choose 6000.
Surface
1 In the Model Builder window, expand the Results>Concentration distribution drug node,
then click Surface.
2 In the Settings window for Surface, locate the Expression section.
3 In the Expression text field, type c_drug.
4 Click the Zoom Extents button on the Graphics toolbar.
5 On the Concentration distribution drug toolbar, click Plot.
The concentration profiles across parts of the modeling domains, as in Figures 5 and 6,
require cut line data sets.
Cut Line 2D 1
1 On the Results toolbar, click Cut Line 2D.
2 In the Settings window for Cut Line 2D, locate the Line Data section.
3 In row Point 1, set Z to 3.
4 In row Point 2, set R to 6 and z to 3.
Cut Line 2D 2
1 On the Results toolbar, click Cut Line 2D.
2 In the Settings window for Cut Line 2D, locate the Line Data section.
3 In row Point 1, set R to 1 and z to 3.
4 In row Point 2, set R to 3 and z to 3.
Concentration (tds)
Create Figure 5 following these steps.
3 Locate the Data section. From the Data set list, choose Cut Line 2D 1.
4 From the Time selection list, choose From list.
5 In the Times (s) list, choose 0, 600, 1200, 1800, 2400, 3000, 3600, 4200, 4800, 5400, and
6000.
6 Click to expand the Title section. From the Title type list, choose None.
7 Locate the Plot Settings section. Select the y-axis label check box.
8 In the associated text field, type c<sub>drug</sub> + c<sub>peptide-drug</sub>
(mol/m<sup>3</sup>).
Line Graph 1
1 Right-click Total drug concentration profiles across modeling domain and choose
Line Graph.
2 In the Settings window for Line Graph, locate the y-Axis Data section.
3 In the Expression text field, type c_peptidedrug+c_drug.
4 Click to expand the Coloring and style section. Locate the Coloring and Style section. In
the Width text field, type 2.
5 Click to expand the Legends section. Select the Show legends check box.
6 On the Total drug concentration profiles across modeling domain toolbar, click Plot.
7 Click the Zoom Extents button on the Graphics toolbar.
1D Plot Group 11
1 On the Home toolbar, click Add Plot Group and choose 1D Plot Group.
2 In the Settings window for 1D Plot Group, type Matrix site concentration
profiles in the Label text field.
3 Locate the Data section. From the Data set list, choose Cut Line 2D 2.
4 From the Time selection list, choose From list.
5 In the Times (s) list, choose 0, 600, 1200, 1800, 2400, 3000, 3600, 4200, 4800, 5400, and
6000.
6 Locate the Title section. From the Title type list, choose None.
9 Click to expand the Legend section. From the Position list, choose Lower right.
Line Graph 1
1 Right-click Matrix site concentration profiles and choose Line Graph.
2 In the Settings window for Line Graph, locate the y-Axis Data section.
3 In the Expression text field, type cmp+cmpd.
4 Locate the Coloring and Style section. In the Width text field, type 2.
5 Locate the Legends section. Select the Show legends check box.
6 On the Matrix site concentration profiles toolbar, click Plot.
7 Click the Zoom Extents button on the Graphics toolbar.
Surface
1 In the Model Builder window, expand the Results>Matrix site concentration node, then
click Surface.
2 In the Settings window for Surface, locate the Expression section.
3 In the Expression text field, type cmp+cmpd.
4 Click the Zoom Extents button on the Graphics toolbar.
5 On the Matrix site concentration toolbar, click Plot.
The following steps show how you can set up animations of your model results.
Animation 1
1 On the Results toolbar, click Animation and choose File.
2 In the Settings window for Animation, type Animation - Concentration
distribution drug in the Label text field.
3 Locate the Scene section. From the Subject list, choose Concentration distribution drug.
4 Locate the Target section. From the Target list, choose Player.
5 Right-click Animation - Concentration distribution drug and choose Play.
3 Locate the Scene section. From the Subject list, choose Matrix site concentration.
4 Locate the Target section. From the Target list, choose Player.
5 Right-click Animation - Matrix site concentration and choose Play.
3D Plot Group 3
In the Model Builder window, under Results right-click 2D Plot Group 2 and choose Delete.
Concentration (tds)
In the Model Builder window, under Results right-click 3D Plot Group 3 and choose Delete.
2D Plot Group 6
In the Model Builder window, under Results right-click Concentration (tds) and choose
Delete.
3D Plot Group 7
In the Model Builder window, under Results right-click 2D Plot Group 6 and choose Delete.
Concentration (tds2) 1
1 In the Model Builder window, under Results right-click 3D Plot Group 7 and choose
Delete.
2 Right-click Concentration (tds2) and choose Delete.
3 Right-click Concentration (tds2) 1 and choose Delete.
For future use of the 0D model, turn off the space-dependent interfaces in the Study 1
node.
STUDY 1
Physics interface
Chemistry - Biomaterial matrix (chem)
Transport of Diluted Species - Biomaterial matrix (tds)
Chemistry - Nerve and Surroundings (chem2)
Transport of Diluted Species - Nerve and Surroundings (tds2)