Mechanical damage is central to both initiation and progression of osteoarthritis (OA). However, specific causal links between mechanics and cartilage damage are incompletely understood, which results in an inability to predict failure. The lack of understanding is primarily due to the difficulty in simultaneously resolving the high rates and small length scales relevant to the problem and in correlating such measurements to the resulting fissures. This study leveraged microscopy and high-speed imaging to resolve mechanics on the previously unexamined time and length scales of interest in cartilage damage, and used those mechanics to develop predictive models. The specific objectives of this study were to: first, quantify bulk and local mechanics during impact-induced fissuring; second, develop predictive models of fissuring based on bulk mechanics and local strain; and third, evaluate the accuracy of these models in predicting fissures. To achieve these three objectives, bovine tibial cartilage was impacted using a custom spring-loaded device mounted on an inverted microscope. The occurrence of fissures was modulated by varying impact energy. For the first objective, during impact, deformation was captured at 10,000 frames per second and bulk and local mechanics were analyzed. For the second objective, data from samples impacted with a 1.2 mm diameter rod were fit to logistic regression functions, creating models of fissure probability based on bulk and local mechanics. Finally, for the third objective, data from samples impacted with a 0.8 mm diameter rod were used to test the accuracy of model predictions. This study provides a direct comparison between bulk and local mechanical thresholds for the prediction of fissures in cartilage samples, and demonstrates that local mechanics provide more accurate predictions of local failure than bulk mechanics provide. Bulk mechanics were accurate predictors of fissure for the entire sample cohort, but poor predictors of fissure for individual samples. Local strain fields were highly heterogeneous and significant differences were determined between fissured and intact samples, indicating the presence of damage thresholds. In particular, first principal strain rate and maximum shear strain were the best predictors of local failure, as determined by concordance statistics. These data provide an important step in establishing causal links between local mechanics and cartilage damage; ultimately, data such as these can be used to link macro- and micro-scale mechanics and thereby predict mechanically mediated disease on a subject-specific basis.

References

References
1.
Buckwalter
,
J. A.
,
Anderson
,
D. D.
,
Brown
,
T. D.
,
Tochigi
,
Y.
, and
Martin
,
J. A.
,
2013
, “
The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis: Implications for Treatment of Joint Injuries
,”
Cartilage
,
4
(
4
), pp.
286
294
.
2.
Kim
,
H. T.
,
Lo
,
M. Y.
, and
Pillarisetty
,
R.
,
2002
, “
Chondrocyte Apoptosis Following Intraarticular Fracture in Humans
,”
Osteoarthritis Cartilage
,
10
(
9
), pp.
747
749
.
3.
Jeffrey
,
J. E.
,
Gregory
,
D. W.
, and
Aspden
,
R. M.
,
1995
, “
Matrix Damage and Chondrocyte Viability Following a Single Impact Load on Articular Cartilage
,”
Arch. Biochem. Biophys.
,
322
(
1
), pp.
87
96
.
4.
Kerin
,
A. J.
,
Coleman
,
A.
,
Wisnom
,
M. R.
, and
Adams
,
M. A.
,
2003
, “
Propagation of Surface Fissures in Articular Cartilage in Response to Cyclic Loading In Vitro
,”
Clin. Biomech.
,
18
(
10
), pp.
960
968
.
5.
Aspden
,
R.
,
2002
, “
Letter to the Editor
,”
Osteoarthritis Cartilage
,
10
(
7
), pp.
588
589
.
6.
Silverberg
,
J. L.
,
Dillavou
,
S.
,
Bonassar
,
L. J.
, and
Cohen
,
I.
,
2013
, “
Anatomic Variation of Depth-Dependent Mechanical Properties in Neonatal Bovine Articular Cartilage
,”
J. Orthop. Res.
,
31
(
5
), pp.
686
691
.
7.
Buckley
,
M. R.
,
Gleghorn
,
J. P.
,
Bonassar
,
L. J.
, and
Cohen
,
I.
,
2008
, “
Mapping the Depth Dependence of Shear Properties in Articular Cartilage
,”
J. Biomech.
,
41
(
11
), pp.
2430
2437
.
8.
Buckley
,
M. R.
,
Bonassar
,
L. J.
, and
Cohen
,
I.
,
2013
, “
Localization of Viscous Behavior and Shear Energy Dissipation in Articular Cartilage Under Dynamic Shear Loading
,”
ASME J. Biomech. Eng.
,
135
(
3
), p.
31002
.
9.
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.
,
34
(
1
), pp.
1
12
.
10.
Chen
,
S. S.
,
Falcovitz
,
Y. H.
,
Schneiderman
,
R.
,
Maroudas
,
A.
, and
Sah
,
R.
,
2001
, “
Depth-Dependent Compressive Properties of Normal Aged Human Femoral Head Articular Cartilage: Relationship to Fixed Charge Density
,”
Osteoarthritis Cartilage
,
9
(
6
), pp.
561
569
.
11.
Backus
,
J. D.
,
Furman
,
B. D.
,
Swimmer
,
T.
,
Kent
,
C. L.
,
Mcnulty
,
A. L.
,
Defrate
,
L. E.
,
Guilak
,
F.
, and
Olson
,
S. A.
,
2012
, “
Cartilage Viability and Catabolism in the Intact Porcine Knee Following Transarticular Impact Loading With and Without Articular Fracture
,”
J. Orthop. Res.
,
29
(
4
), pp.
501
510
.
12.
Bolam
,
C. J.
,
Hurtig
,
M. B.
,
Cruz
,
A.
, and
McEwen
,
B. J. E.
,
2006
, “
Characterization of Experimentally Induced Post-Traumatic Osteoarthritis in the Medial Femorotibial Joint of Horses
,”
Am. J. Vet. Res.
,
67
(
3
), pp.
433
447
.
13.
Heiner
,
A. D.
,
Smith
,
A. D.
,
Goetz
,
J. E.
,
Goreham-Voss
,
C. M.
,
Judd
,
K. T.
,
McKinley
,
T. O.
, and
Martin
,
J. A.
,
2013
, “
Cartilage-on-Cartilage Versus Metal-on-Cartilage Impact Characteristics and Responses
,”
J. Orthop. Res.
,
31
(
6
), pp.
887
893
.
14.
Milentijevic
,
D.
, and
Torzilli
,
P. A.
,
2005
, “
Influence of Stress Rate on Water Loss, Matrix Deformation and Chondrocyte Viability in Impacted Articular Cartilage
,”
J. Biomech.
,
38
(
3
), pp.
493
502
.
15.
Milentijevic
,
D.
,
Helfet
,
D. L.
, and
Torzilli
,
P. A.
,
2003
, “
Influence of Stress Magnitude on Water Loss and Chondrocyte Viability in Impacted Articular Cartilage
,”
ASME J. Biomech. Eng.
,
125
(
5
), p.
594
.
16.
Torzilli
,
P. A.
,
Grigiene
,
R.
,
Borrelli
,
J.
, and
Helfet
,
D. L.
,
1999
, “
Effect of Impact Load on Articular Cartilage: Cell Metabolism and Viability, and Matrix Water Content
,”
ASME J. Biomech. Eng.
,
121
(
5
), pp.
433
441
.
17.
Borrelli
,
J.
,
Tinsley
,
K.
,
Ricci
,
W. M.
,
Burns
,
M.
,
Karl
,
I. E.
, and
Hotchkiss
,
R.
,
2003
, “
Induction of Chondrocyte Apoptosis Following Impact Load
,”
J. Orthop. Trauma
,
17
(
9
), pp.
635
641
.
18.
Borrelli
,
J.
,
Zhu
,
Y.
,
Burns
,
M.
,
Sandell
,
L.
, and
Silva
,
M. J.
,
2004
, “
Cartilage Tolerates Single Impact Loads of as Much as Half the Joint Fracture Threshold
,”
Clin. Orthop. Relat. Res.
,
426
, pp.
266
273
.
19.
Borrelli
,
J.
,
Silva
,
M. J.
,
Zaegel
,
M. A.
,
Franz
,
C.
, and
Sandell
,
L. J.
,
2009
, “
Single High-Energy Impact Load Causes Posttraumatic OA in Young Rabbits Via a Decrease in Cellular Metabolism
,”
J. Orthop. Res.
,
27
(
3
), pp.
347
352
.
20.
Borrelli
,
J.
,
Zaegel
,
M. A.
,
Martinez
,
M. D.
, and
Silva
,
M. J.
,
2010
, “
Diminished Cartilage Creep Properties and Increased Trabecular Bone Density Following a Single, Sub-Fracture Impact of the Rabbit Femoral Condyle
,”
J. Orthop. Res.
,
28
(
10
), pp.
1307
1314
.
21.
Ewers
,
B. J.
,
Newberry
,
W. N.
, and
Haut
,
R. C.
,
2000
, “
Chronic Softening of Cartilage Without Thickening of Underlying Bone in a Joint Trauma Model
,”
J. Biomech.
,
33
(
12
), pp.
1689
1694
.
22.
Newberry
,
W. N.
,
Garcia
,
J. J.
,
Mackenzie
,
C. D.
,
Decamp
,
D. E.
, and
Haut
,
R. C.
,
1998
, “
Analysis of Acute Mechanical Insult in an Animal Model of Post-Traumatic Osteoarthritis
,”
ASME J. Biomech. Eng.
,
120
(
12
), pp.
704
709
.
23.
Haut
,
R.
,
Ide
,
T.
, and
De Camp
,
C.
,
1995
, “
Mechanical Responses of the Rabbit Patello-Femoral Joint to Blunt Impact
,”
ASME J. Biomech. Eng.
,
117
(
11
), pp.
402
408
.
24.
Ewers
,
B. J.
,
Jayaraman
,
V. M.
,
Banglmaier
,
R. F.
, and
Haut
,
R. C.
,
2002
, “
Rate of Blunt Impact Loading Affects Changes in Retropatellar Cartilage and Underlying Bone in the Rabbit Patella
,”
J. Biomech.
,
35
(
6
), pp.
747
755
.
25.
Burgin
,
L. V.
, and
Aspden
,
R. M.
,
2008
, “
Impact Testing to Determine the Mechanical Properties of Articular Cartilage in Isolation and on Bone
,”
J. Mater. Sci.: Mater. Med.
,
19
(
2
), pp.
703
711
.
26.
Lee
,
C. M.
,
Kisiday
,
J. D.
,
McIlwraith
,
C. W.
,
Grodzinsky
,
A. J.
, and
Frisbie
,
D. D.
,
2013
, “
Development of an In Vitro Model of Injury-Induced Osteoarthritis in Cartilage Explants From Compressive Overload
,”
Am. J. Vet. Res.
,
74
(
1
), pp.
40
47
.
27.
Repo
,
R.
, and
Finlay
,
J.
,
1977
, “
Survival of Articular Cartilage After Controlled Impact
,”
J. Bone Jt. Surg.
, Am.,
59
(
8
), pp.
1068
1076
.http://jbjs.org/content/59/8/1068
28.
Patwari
,
P.
,
Cheng
,
D. M.
,
Cole
,
A. A.
,
Kuettner
,
K. E.
, and
Grodzinsky
,
A. J.
,
2007
, “
Analysis of the Relationship Between Peak Stress and Proteoglycan Loss Following Injurious Compression of Human Post-Mortem Knee and Ankle Cartilage
,”
Biomech. Model. Mechanobiol.
,
6
(
1–2
), pp.
83
89
.
29.
Kim
,
W.
,
Thambyah
,
A.
, and
Broom
,
N.
,
2012
, “
Does Prior Sustained Compression Make Cartilage-on-Bone More Vulnerable to Trauma?
,”
Clin. Biomech. (Bristol, Avon)
,
27
(
7
), pp.
637
645
.
30.
Thambyah
,
A.
,
Shim
,
V. P. W.
,
Chong
,
L. M.
, and
Lee
,
V. S.
,
2008
, “
Impact-Induced Osteochondral Fracture in the Tibial Plateau
,”
J. Biomech.
,
41
(
6
), pp.
1236
1242
.
31.
Ewers
,
B. J.
,
Weaver
,
B. T.
, and
Haut
,
R. C.
,
2002
, “
Impact Orientation Can Significantly Affect the Outcome of a Blunt Impact to the Rabbit Patellofemoral Joint
,”
J. Biomech.
,
35
(
12
), pp.
1591
1598
.
32.
Leucht
,
F.
,
Dürselen
,
L.
,
Hogrefe
,
C.
,
Joos
,
H.
,
Reichel
,
H.
,
Schmitt
,
H.
,
Ignatius
,
A.
, and
Brenner
,
R. E.
,
2012
, “
Development of a New Biomechanically Defined Single Impact Rabbit Cartilage Trauma Model for In Vivo-Studies
,”
J. Invest. Surg.
,
25
(
4
), pp.
235
241
.
33.
Natoli
,
R. M.
,
Scott
,
C. C.
, and
Athanasiou
,
K. A.
,
2008
, “
Temporal Effects of Impact on Articular Cartilage Cell Death, Gene Expression, Matrix Biochemistry, and Biomechanics
,”
Ann. Biomed. Eng.
,
36
(
5
), pp.
780
792
.
34.
Verteramo
,
A.
, and
Seedhom
,
B. B.
,
2007
, “
Effect of a Single Impact Loading on the Structure and Mechanical Properties of Articular Cartilage
,”
J. Biomech.
,
40
(
16
), pp.
3580
3589
.
35.
Patwari
,
P.
,
Cheng
,
D. M.
,
Cole
,
A. A.
,
Kuettner
,
K. E.
, and
Grodzinsky
,
A. J.
,
2007
, “
Analysis of the Relationship Between Peak Stress and Proteoglycan Loss Following Injurious Compression of Human Post-Mortem Knee and Ankle Cartilage
,”
Biomech. Model. Mechanobiol.
,
6
(
1–2
), pp.
83
89
.
36.
Atkinson
,
T.
,
Haut
,
R.
, and
Altiero
,
N.
,
1998
, “
Impact-Induced Fissuring of Articular Cartilage: An Investigation of Failure Criteria
,”
ASME J. Biomech. Eng.
,
120
(
2
), pp.
181
187
.
37.
Bartell
,
L. R.
,
Fortier
,
L. A.
,
Bonassar
,
L. J.
, and
Cohen
,
I.
,
2015
, “
Measuring Microscale Strain Fields in Articular Cartilage During Rapid Impact Reveals Thresholds for Chondrocyte Death and a Protective Role for the Superficial Layer
,”
J. Biomech.
,
48
(
12
), pp.
3440
3446
.
38.
Jones
,
E. M. C.
,
Silberstein
,
M. N.
,
White
,
S. R.
, and
Sottos
,
N. R.
,
2014
, “
In Situ Measurements of Strains in Composite Battery Electrodes During Electrochemical Cycling
,”
Exp. Mech.
,
54
(
6
), pp.
971
985
.
39.
Jones
,
E. M. C.
,
2013
, “
Improved Digital Image Correlation
,” MatLab Central, Natick, MA, Aug. 14, accessed Dec. 14, 2014, http://www.mathworks.com/matlabcentral/fileexchange/43073-improved-digital-image-correlation–dic-
40.
Kafka
,
V.
,
2002
, “
Surface Fissures in Articular Cartilage: New Concepts, Hypotheses and Modeling
,”
Clin. Biomech.
,
17
(
1
), pp.
73
80
.
41.
Hadi
,
M. F.
,
Sander
,
E. A.
, and
Barocas
,
V. H.
,
2012
, “
Multiscale Model Predicts Tissue-Level Failure From Collagen Fiber-Level Damage
,”
ASME J. Biomech. Eng.
,
134
(
9
), pp.
091005
091005-10
.
42.
Beer
,
F. P.
,
Johnston
,
E. R.
, Jr.
,
DeWolf
,
J. T.
, and
Mazurek
,
D. F.
,
2012
,
Mechanics of Materials
,
McGraw-Hill Education
,
New York
.
43.
Atkinson
,
T.
,
Haut
,
R.
, and
Altiero
,
N.
,
1998
, “
An Investigation of Biphasic Failure Criteria for Impact-Induced Fissuring of Articular Cartilage
,”
ASME J. Biomech. Eng.
,
120
(
4
), pp.
536
537
.
44.
Morel
,
V.
, and
Quinn
,
T. M.
,
2004
, “
Cartilage Injury by Ramp Compression Near the Gel Diffusion Rate
,”
J. Orthop. Res.
,
22
(
1
), pp.
145
151
.
45.
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 Experiments
,”
ASME J. Biomech. Eng.
,
102
(
1
), pp.
73
84
.
46.
Huang
,
C.-Y.
,
Soltz
,
M. A.
,
Kopacz
,
M.
,
Mow
,
V. C.
, and
Ateshian
,
G. A.
,
2003
, “
Experimental Verification of the Roles of Intrinsic Matrix Viscoelasticity and Tension-Compression Nonlinearity in the Biphasic Response of Cartilage
,”
ASME J. Biomech. Eng.
,
125
(
1
), pp.
84
93
.
47.
Brand
,
R. A.
,
2005
, “
Joint Contact Stress: A Reasonable Surrogate for Biological Processes?
,”
Iowa Orthop. J.
,
25
, pp.
82
94
.https://www.ncbi.nlm.nih.gov/pubmed/16089079
48.
Hosmer
,
D. W.
, and
Lemeshow
,
S.
,
2000
,
Applied Logistic Regression
,
Wiley
,
Hoboken, NJ
.
49.
Finner
,
H.
,
1993
, “
On a Monotonicity Problem in Step-Down Multiple Test Procedures
,”
J. Am. Stat. Assoc.
,
88
(
423
), pp.
920
923
.
50.
Steyerberg
,
E. W.
,
Vickers
,
A. J.
,
Cook
,
N. R.
,
Gerds
,
T.
,
Obuchowski
,
N.
,
Pencina
,
M. J.
, and
Kattan
,
M. W.
,
2010
, “
Assessing the Performance of Prediction Models: A Framework for Some Traditional and Novel Measures
,”
Epidemiology
,
21
(
1
), pp.
128
138
.
51.
Tang
,
Y.
,
Ballarini
,
R.
,
Buehler
,
M. J.
, and
Eppell
,
S. J.
,
2010
, “
Deformation Micromechanisms of Collagen Fibrils Under Uniaxial Tension
,”
J. R. Soc., Interface
,
7
(
46
), pp.
839
850
.
52.
Shen
,
Z. L.
,
Dodge
,
M. R.
,
Kahn
,
H.
,
Ballarini
,
R.
, and
Eppell
,
S. J.
,
2010
, “
in vitro Fracture Testing of Submicron Diameter Collagen Fibril Specimens
,”
Biophys. J.
,
99
(
6
), pp.
1986
1995
.
53.
Silyn-Roberts
,
H.
, and
Broom
,
N. D.
,
1990
, “
Fracture Behavior of Cartilage-on-Bone in Response to Repeated Impact Loading
,”
Connect. Tissue Res.
,
24
(
2
), pp.
143
156
.
54.
Dasari
,
A.
, and
Misra
,
R. D. K.
,
2003
, “
On the Strain Rate Sensitivity of High Density Polyethylene and Polypropylenes
,”
Mater. Sci. Eng.: A
,
358
(
1–2
), pp.
356
371
.
55.
Novakofski
,
K. D.
,
Williams
,
R. M.
,
Fortier
,
L. A.
,
Mohammed
,
H. O.
,
Zipfel
,
W. R.
, and
Bonassar
,
L. J.
,
2014
, “
Identification of Cartilage Injury Using Quantitative Multiphoton Microscopy
,”
Osteoarthritis Cartilage
,
22
(
2
), pp.
355
362
.
56.
Lewis
,
J. L.
,
Deloria
,
L. B.
,
Oyen-Tiesma
,
M.
,
Thompson
,
R. C.
,
Ericson
,
M.
, and
Oegema
,
T. R.
,
2003
, “
Cell Death After Cartilage Impact Occurs Around Matrix Cracks
,”
J. Orthop. Res.
,
21
(
5
), pp.
881
887
.
57.
Ewers
,
B. J.
,
Dvoracek-Driksna
,
D.
,
Orth
,
M. W.
, and
Haut
,
R. C.
,
2001
, “
The Extent of Matrix Damage and Chondrocyte Death in Mechanically Traumatized Articular Cartilage Explants Depends on Rate of Loading
,”
J. Orthop. Res.
,
19
(
5
), pp.
779
784
.
58.
Martin
,
J. A.
,
Brown
,
T.
,
Heiner
,
A.
, and
Buckwalter
,
J. A.
,
2004
, “
Post-Traumatic Osteoarthritis: The Role of Accelerated Chondrocyte Senescence
,”
Biorheology
,
41
(3–4), pp.
479
491
.http://content.iospress.com/articles/biorheology/bir315
59.
Mow
,
V. C.
, and
Huiskes
,
R.
,
2005
,
Basic Orthopaedic Biomechanics and Mechano-Biology
,
Lippincott Williams & Wilkins
,
Philadelphia, PA
.
60.
Buckley
,
M. R.
,
Bergou
,
A. J.
,
Fouchard
,
J.
,
Bonassar
,
L. J.
, and
Cohen
,
I.
,
2010
, “
High-Resolution Spatial Mapping of Shear Properties in Cartilage
,”
J. Biomech.
,
43
(
4
), pp.
796
800
.
You do not currently have access to this content.