Recently a cartilage growth finite element model (CGFEM) was developed to solve nonhomogeneous and time-dependent growth boundary-value problems (Davol et al., 2008, “A Nonlinear Finite Element Model of Cartilage Growth,” Biomech. Model. Mechanobiol., 7, pp. 295–307). The CGFEM allows distinct stress constitutive equations and growth laws for the major components of the solid matrix, collagens and proteoglycans. The objective of the current work was to simulate in vitro growth of articular cartilage explants in a steady-state permeation bioreactor in order to obtain results that aid experimental design. The steady-state permeation protocol induces different types of mechanical stimuli. When the specimen is initially homogeneous, it directly induces homogeneous permeation velocities and indirectly induces nonhomogeneous solid matrix shear stresses; consequently, the steady-state permeation protocol is a good candidate for exploring two competing hypotheses for the growth laws. The analysis protocols were implemented through the alternating interaction of the two CGFEM components: poroelastic finite element analysis (FEA) using ABAQUS and a finite element growth routine using MATLAB. The CGFEM simulated 12 days of growth for immature bovine articular cartilage explants subjected to two competing hypotheses for the growth laws: one that is triggered by permeation velocity and the other by maximum shear stress. The results provide predictions for geometric, biomechanical, and biochemical parameters of grown tissue specimens that may be experimentally measured and, consequently, suggest key biomechanical measures to analyze as pilot experiments are performed. The combined approach of CGFEM analysis and pilot experiments may lead to the refinement of actual experimental protocols and a better understanding of in vitro growth of articular cartilage.

1.
Buckwalter
,
J. A.
, and
Mankin
,
H. J.
, 1998, “
Articular Cartilage Repair and Transplantation
,”
Arthritis Rheum.
0004-3591,
41
, pp.
1331
1342
.
2.
Temenoff
,
J. S.
, and
Mikos
,
A. G.
, 2000, “
Review: Tissue Engineering for Regeneration of Articular Cartilage
,”
Biomaterials
0142-9612,
21
(
5
), pp.
431
440
.
3.
Smith
,
G. D.
,
Knutsen
,
G.
, and
Richardson
,
J. B.
, 2005, “
A Clinical Review of Cartilage Repair Techniques
,”
J. Bone Joint Surg. Br.
,
87B
(
4
), pp.
445
449
. 0301-620X
4.
Hunziker
,
E. B.
, 2002, “
Articular Cartilage Repair: Basic Science and Clinical Progress. A Review of the Current Status and Prospects
,”
Osteoarthritis Cartilage
,
10
, pp.
432
463
. 1063-4584
5.
Mow
,
V. C.
,
Kuei
,
S. C.
,
Lai
,
W. M.
, and
Armstrong
,
C. G.
, 1980, “
Biphasic Creep and Stress Relaxation of Articular Cartilage in Compression: Theory and Experiment
,”
ASME J. Biomech. Eng.
,
102
, pp.
73
84
. 0148-0731
6.
Klisch
,
S. M.
,
Asanbaeva
,
A.
,
Oungoulian
,
S. R.
,
Thonar
,
E. J.
,
Masuda
,
K.
,
Davol
,
A.
, and
Sah
,
R. L.
, 2008, “
A Cartilage Growth Mixture Model With Collagen Remodeling: Validation Protocols
,”
ASME J. Biomech. Eng.
0148-0731,
130
, p.
031006
.
7.
DiMicco
,
M. A.
, and
Sah
,
R. L.
, 2003, “
Dependence of Cartilage Matrix Composition on Biosynthesis, Diffusion, and Reaction
,”
Transp. Porous Media
0169-3913,
50
, pp.
57
73
.
8.
Obradovic
,
B.
,
Meldon
,
J. H.
,
Freed
,
L. E.
, and
Vunjak-Novakovic
,
G.
, 2000, “
Glycosaminoglycan Deposition in Engineered Cartilage: Experiments and Mathematical Model
,”
AIChE J.
0001-1541,
46
(
9
), pp.
1860
1871
.
9.
Wilson
,
C. G.
,
Bonassar
,
L. J.
, and
Kohles
,
S. S.
, 2002, “
Modeling the Dynamic Composition of Engineered Cartilage
,”
Arch. Biochem. Biophys.
0003-9861,
408
(
2
), pp.
246
254
.
10.
Sengers
,
B. G.
,
Oomens
,
C. W. J.
,
Nguyen
,
T. Q. D.
, and
Bader
,
D. L.
, 2006, “
Computational Modeling to Predict the Temporal Regulation of Chondrocyte Metabolism in Response to Various Dynamic Compression Regimens
,”
Biomech. Model. Mechanobiol.
,
5
, pp.
111
122
. 1617-7959
11.
Carter
,
D. R.
, and
Wong
,
M.
, 2003, “
Modelling Cartilage Mechanobiology
,”
Philos. Trans. R. Soc. London, Ser. B
,
358
(
1437
), pp.
1461
1471
. 0962-8436
12.
Kohles
,
S. S.
,
Wilson
,
C. G.
, and
Bonassar
,
L. J.
, 2007, “
A Mechanical Composite Spheres Analysis of Engineered Cartilage Dynamics
,”
ASME J. Biomech. Eng.
0148-0731,
129
, pp.
473
480
.
13.
Kuhl
,
E.
, and
Steinmann
,
P.
, 2003, “
Mass- and Volume-Specific Views on Thermodynamics for Open Systems
,”
Proc. Trans. R. Soc. London, Ser. A
,
459A
, pp.
2547
2568
. 0370-1662
14.
Menzel
,
A.
, 2005, “
Modelling of Anisotropic Growth in Biological Tissues: A New Approach and Computational Aspects
,”
Biomech. Model. Mechanobiol.
,
3
(
3
), pp.
147
171
. 1617-7959
15.
Humphrey
,
J. D.
, and
Rajagopal
,
K. R.
, 2002, “
A Constrained Mixture Model for Growth and Remodeling in Soft Tissues
,”
Math. Models Meth. Appl. Sci.
0218-2025,
12
(
3
), pp.
407
430
.
16.
Garikipati
,
K.
,
Arruda
,
E. M.
,
Grosh
,
K.
,
Narayanan
,
H.
, and
Calve
,
S.
, 2004, “
A Continuum Treatment of Growth in Biological Tissue: The Coupling of Mass Transport and Growth
,”
J. Mech. Phys. Solids
0022-5096,
52
(
7
), pp.
1595
1625
.
17.
Klisch
,
S. M.
,
DiMicco
,
M. A.
,
Hoger
,
A.
, and
Sah
,
R. L.
, 2003, “
Bioengineering the Growth of Articular Cartilage
,”
Functional Tissue Engineering
,
F.
Guilak
,
D.
Butler
,
D.
Mooney
, and
S.
Goldstein
, eds.,
Springer-Verlag
,
New York
, pp.
194
210
.
18.
Bingham
,
M.
,
Davol
,
A.
,
Sah
,
R. L.
, and
Klisch
,
S. M.
, 2005, “
A Nonlinear Finite Element Model of Cartilage Growth Under In Vitro Dynamic Compression
,”
ASME Summer Bioengineering Conference
.
19.
Davol
,
A.
,
Bingham
,
M. S.
,
Sah
,
R. L.
, and
Klisch
,
S. M.
, 2008, “
A Nonlinear Finite Element Model of Cartilage Growth
,”
Biomech. Model. Mechanobiol.
1617-7959,
7
, pp.
295
307
.
20.
Klisch
,
S. M.
, 2006, “
Continuum Models of Growth With Special Emphasis on Articular Cartilage
,”
Mechanics of Biological Tissue
,
G. A.
Holzapfel
and
R. W.
Ogden
, eds.,
Springer-Verlag
,
Berlin
, pp.
119
133
.
21.
Schinagl
,
R. M.
,
Gurskis
,
D.
,
Chen
,
A. C.
, and
Sah
,
R. L.
, 1997, “
Depth-Dependent Confined Compression Modulus of Full-Thickness Bovine Articular Cartilage
,”
J. Orthop. Res.
0736-0266,
15
, pp.
499
506
.
22.
Holmes
,
M. H.
, and
Mow
,
V. C.
, 1990, “
The Nonlinear Characteristics of Soft Gels and Hydrated Connective Tissue in Ultrafiltration
,”
J. Biomech.
0021-9290,
23
, pp.
1145
1156
.
23.
Gu
,
W. Y.
,
Sun
,
D. N.
,
Lai
,
W. M.
, and
Mow
,
V. C.
, 2004, “
Analysis of the Dynamic Permeation Experiment With Implication to Cartilaginous Tissue Engineering
,”
ASME J. Biomech. Eng.
0148-0731,
126
, pp.
485
491
.
24.
Kim
,
Y. J.
,
Bonassar
,
L. J.
, and
Grodzinsky
,
A. J.
, 1995, “
The Role of Cartilage Streaming Potential, Fluid Flow and Pressure in the Stimulation of Chondrocyte Biosynthesis During Dynamic Compression
,”
J. Biomech.
0021-9290,
28
, pp.
1055
1066
.
25.
Buschmann
,
M. D.
,
Kim
,
Y. J.
,
Wong
,
M.
,
Frank
,
E.
,
Hunziker
,
E. B.
, and
Grodzinsky
,
A. J.
, 1999, “
Stimulation of Aggrecan Synthesis in Cartilage Explants by Cyclic Loading is Localized to Regions of High Interstitial Fluid Flow
,”
Arch. Biochem. Biophys.
0003-9861,
366
, pp.
1
7
.
26.
Davisson
,
T. H.
,
Sah
,
R. L.
, and
Ratcliffe
,
A. R.
, 2002, “
Perfusion Increases Cell Content and Matrix Synthesis in Chondrocyte Three-Dimensional Cultures
,”
Tissue Eng.
1076-3279,
8
, pp.
807
816
.
27.
Pazzano
,
D.
,
Mercier
,
K. A.
,
Moran
,
J. M.
,
Fong
,
S. S.
,
DiBiasio
,
D. D.
,
Rulfs
,
J. X.
,
Kohles
,
S. S.
, and
Bonassar
,
L. J.
, 2000, “
Comparison of Chondrogensis in Static and Perfused Bioreactor Culture
,”
Biotechnol. Prog.
8756-7938,
16
(
5
), pp.
893
896
.
28.
Jin
,
M.
,
Emkey
,
G. R.
,
Siparsky
,
P.
,
Trippel
,
S. B.
, and
Grodzinsky
,
A. J.
, 2003, “
Combined Effects of Dynamic Tissue Shear Deformation and Insulin-Like Growth Factor I on Chondrocyte Biosynthesis in Cartilage Explants
,”
Arch. Biochem. Biophys.
,
414
(
2
), pp.
223
231
. 0003-9861
29.
Strehl
,
R.
,
Tallheden
,
T.
,
Sjogren-Jansson
,
E.
,
Minuth
,
W. W.
, and
Lindahl
,
A.
, 2005, “
Long-Term Maintenance of Human Articular Cartilage in Culture for Biomaterial Testing
,”
Biomaterials
,
26
, pp.
4540
4549
. 0142-9612
30.
Klisch
,
S. M.
, and
Lotz
,
J. C.
, 2000, “
A Special Theory of Biphasic Mixtures and Experimental Results for Human Annulus Fibrosus Tested in Confined Compression
,”
ASME J. Biomech. Eng.
0148-0731,
122
, pp.
180
188
.
31.
Klisch
,
S. M.
,
Van Dyke
,
T.
, and
Hoger
,
A.
, 2001, “
A Theory of Volumetric Growth for Compressible Elastic Materials
,”
Math. Mech. Solids
1081-2865,
6
, pp.
551
575
.
32.
Klisch
,
S. M.
,
Chen
,
S. S.
,
Sah
,
R. L.
, and
Hoger
,
A.
, 2003, “
A Growth Mixture Theory for Cartilage With Applications to Growth-Related Experiments on Cartilage Explants
,”
ASME J. Biomech. Eng.
0148-0731,
125
, pp.
169
179
.
33.
Klisch
,
S. M.
, and
Hoger
,
A.
, 2003, “
Volumetric Growth of Thermoelastic Materials and Mixtures
,”
Math. Mech. Solids
1081-2865,
8
, pp.
377
402
.
34.
Chen
,
Y. C.
, and
Hoger
,
A.
, 2000, “
Constitutive Functions for Elastic Materials in Finite Growth and Deformation
,”
J. Elast.
0374-3535,
59
, pp.
175
193
.
35.
Klisch
,
S. M.
, 2007, “
A Bimodular Polyconvex Anisotropic Strain Energy Function for Articular Cartilage
,”
ASME J. Biomech. Eng.
0148-0731,
129
, pp.
250
258
.
36.
Oungoulian
,
S. R.
,
Chen
,
S. S.
,
Davol
,
A.
,
Sah
,
R. L.
, and
Klisch
,
S. M.
, 2007, “
Extended Two-Compartmental Swelling Stress Model and Isotropic Cauchy Stress Equation for Articular Cartilage Proteoglycans
,”
ASME Summer Bioengineering Conference
, Keystone, CO.
37.
Asanbaeva
,
A.
,
Masuda
,
K.
,
Thonar
,
E. J.-M. A.
,
Klisch
,
S. M.
, and
Sah
,
R. L.
, 2008, “
Cartilage Growth and Remodeling: Modulation of Balance Between Proteoglycan and Collagen In Vitro With Beta-Aminopropionitrile
,”
Osteoarthritis Cartilage
,
16
, pp.
1
11
. 1063-4584
38.
Sah
,
R. L.
,
Kim
,
Y. J.
,
Doong
,
J. H.
,
Grodzinsky
,
A. J.
,
Plaas
,
A. H. K.
, and
Sandy
,
J. D.
, 1989, “
Biosynthetic Response of Cartilage Explants to Dynamic Compression
,”
J. Orthop. Res.
0736-0266,
7
, pp.
619
636
.
39.
Kim
,
Y. J.
,
Sah
,
R. L.
,
Grodzinsky
,
A. J.
,
Plaas
,
A. H.
, and
Sandy
,
J. D.
, 1994, “
Mechanical Regulation of Cartilage Biosynthetic Behavior: Physical Stimuli
,”
Arch. Biochem. Biophys.
0003-9861,
311
, pp.
1
12
.
40.
Jin
,
M.
,
Frank
,
E. H.
,
Quinn
,
T. M.
,
Hunziker
,
E. B.
, and
Grodzinsky
,
A. J.
, 2001, “
Tissue Shear Deformation Stimulates Proteoglycan and Protein Biosynthesis in Bovine Cartilage Explants
,”
Arch. Biochem. Biophys.
0003-9861,
395
(
1
), pp.
41
48
.
41.
Basser
,
P. J.
,
Schneiderman
,
R.
,
Bank
,
R. A.
,
Wachtel
,
E.
, and
Maroudas
,
A.
, 1998, “
Mechanical Properties of the Collagen Network in Human Articular Cartilage as Measured by Osmotic Stress Technique
,”
Arch. Biochem. Biophys.
0003-9861,
351
, pp.
207
219
.
42.
Williamson
,
A. K.
,
Chen
,
A. C.
, and
Sah
,
R. L.
, 2001, “
Compressive Properties and Function-Composition Relationships of Developing Bovine Articular Cartilage
,”
J. Orthop. Res.
0736-0266,
19
, pp.
1113
1121
.
43.
Klisch
,
S. M.
,
Asanbaeva
,
A.
,
Oungoulian
,
S. R.
,
Thonar
,
E. J.
,
Masuda
,
K.
,
Davol
,
A.
, and
Sah
,
R. L.
, 2007, “
A Cartilage Growth Mixture Model With Collagen Remodeling: Validation Protocols
,”
ASME Summer Bioengineering Conference
.
44.
Ficklin
,
T. P.
,
Thomas
,
G. C.
,
Barthel
,
J. C.
,
Asanbaeva
,
A.
,
Thonar
,
E. J.
,
Masuda
,
K.
,
Chen
,
A. C.
,
Sah
,
R. L.
,
Davol
,
A.
, and
Klisch
,
S. M.
, 2007, “
Articular Cartilage Mechanical and Biochemical Property Relations Before and After In Vitro Growth
,”
J. Biomech.
0021-9290,
40
, pp.
3607
3614
.
45.
Chen
,
A. C.
,
Bae
,
W. C.
,
Schinagl
,
R. M.
, and
Sah
,
R. L.
, 2001, “
Depth- and Strain-Dependent Mechanical and Electromechanical Properties of Full-Thickness Bovine Articular Cartilage in Confined Compression
,”
J. Biomech.
0021-9290,
34
, pp.
1
12
.
46.
Frank
,
E. H.
, and
Grodzinsky
,
A. J.
, 1987, “
Cartilage Electromechanics-II. A Continuum Model of Cartilage Electrokinetics and Correlation With Experiments
,”
J. Biomech.
0021-9290,
20
, pp.
629
639
.
47.
Morel
,
V.
, and
Quinn
,
T. M.
, 2004, “
Cartilage Injury by Ramp Compression Near the Gel Diffusion Rate
,”
J. Orthop. Res.
0736-0266,
22
, pp.
145
151
.
48.
Asanbaeva
,
A.
,
Masuda
,
K.
,
Thonar
,
E. J.-M. A.
,
Klisch
,
S. M.
, and
Sah
,
R. L.
, 2007, “
Mechanisms of Cartilage Growth: Modulation of Balance Between Proteoglycan and Collagen In Vitro Using Chondroitinase ABC
,”
Arthritis Rheum.
,
56
, pp.
188
198
. 0004-3591
49.
Asanbaeva
,
A.
,
Masuda
,
K.
,
Thonar
,
E. J.-M. A.
,
Klisch
,
S. M.
, and
Sah
,
R. L.
, 2008, “
Regulation of Immature Cartilage Growth by IGF-I, TGF-Alpha 1, BMP-7, and PDGF-AB: Role of Metabolic Balance Between Fixed Charge and Collagen Network
,”
Biomech. Model. Mechanobiol.
,
7
, pp.
263
276
.
50.
Buschmann
,
M. D.
,
Gluzband
,
Y. A.
,
Grodzinsky
,
A. J.
,
Kimura
,
J. H.
, and
Hunziker
,
E. B.
, 1992, “
Chondrocytes in Agarose Culture Synthesize a Mechanically Functional Extracellular Matrix
,”
J. Orthop. Res.
0736-0266,
10
, pp.
745
758
.
51.
Williamson
,
A. K.
,
Masuda
,
K.
,
Thonar
,
E. J.-M. A.
, and
Sah
,
R. L.
, 2003, “
Growth of Immature Articular Cartilage In Vitro: Correlated Variation in Tensile Biomechanical and Collagen Network Properties
,”
Tissue Eng.
1076-3279,
9
, pp.
625
634
.
52.
Bursac
,
P.
,
McGrath
,
C. V.
,
Eisenberg
,
S. R.
, and
Stamenovic
,
D.
, 2000, “
A Microstructural Model of Elastostatic Properties of Articular Cartilage in Confined Compression
,”
ASME J. Biomech. Eng.
0148-0731,
122
, pp.
347
353
.
53.
Chen
,
S. S.
,
Falcovitz
,
Y. H.
,
Schneiderman
,
R.
,
Maroudas
,
A.
, and
Sah
,
R. L.
, 2001, “
Depth-Dependent Compressive Properties of Normal Aged Human Femoral Head Articular Cartilage: Relationship to Fixed Charge Density
,”
Osteoarthritis Cartilage
,
9
, pp.
561
569
. 1063-4584
54.
Chahine
,
N. O.
,
Wang
,
C. C.
,
Hung
,
C. T.
, and
Ateshian
,
G. A.
, 2004, “
Anisotropic Strain-Dependent Material Properties of Bovine Articular Cartilage in the Transitional Range From Tension to Compression
,”
J. Biomech.
0021-9290,
37
, pp.
1251
1261
.
55.
Maroudas
,
A.
, 1976, “
Balance Between Swelling Pressure and Collagen Tension in Normal and Degenerate Cartilage
,”
Nature (London)
0028-0836,
260
, pp.
808
809
.
56.
Wilson
,
W.
,
Huyghe
,
J. M.
, and
van Donkelaar
,
C. C.
, 2007, “
Depth-Dependent Compressive Equilibrium Properties of Articular Cartilage Explained by Its Composition
,”
Biomech. Model. Mechanobiol.
,
6
, pp.
43
53
. 1617-7959
57.
Hangody
,
L.
, and
Fules
,
P.
, 2003, “
Autologous Osteochondral Mosaicplasty for the Treatment of Full-Thickness Defects of Weight-Bearing Joints. Ten Years of Experimental and Clinical Experience
,”
J. Bone Jt. Surg. Am.
,
85-A
, (
2
), pp.
25
32
. 0021-9355
58.
Horas
,
U.
,
Pelinkovic
,
D.
,
Herr
,
G.
,
Aigner
,
T.
, and
Schnettler
,
R.
, 2003, “
Autologous Chondrocyte Implantation and Osteochondral Cylinder Transplantation in Cartilage Repair of the Knee Joint. A Prospective, Comparative Trial
,”
J. Bone Jt. Surg. Am.
,
85-A
(
2
), pp.
185
192
. 0021-9355
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