Chapter Aorta TCG

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Aorta
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Aorta
T.Christian Gasser
KTH Solid Mechanics, School of Engineering Sciences
KTH Royal Institute of Technology, Stockholm, Sweden
June 28, 2017
Abstract
The aorta is a dynamic structure that is able to maintain condi-
tions for optimal mechanical operation through the continuous turnover
of its internal structure. The aorta’s properties are critical to the entire
cardiovascular system, and the study of its biomechanics may, amongst
others, help to understand the role of tissue stress and strain in aortic
aging and pathology, help to optimize medical devices, and improve ther-
apeutic and diagnostic methods that are currently used in clinics. The
present chapter reviews aortic wall histology and morphology in relation
to its key mechanical properties. Specifically, the biomechanical role of
cells (endothelial cells, smooth muscle cells, fibroblasts, etc.) as well as the
extracellular matrix components (elastin, collagen, proteoglycans, water,
etc.) will be discussed. Then this information is related to reported con-
stitutive descriptions for aortic tissues. The focus is on histo-mechanical
approaches and modeling frames, related to hyperelasticity as well as a
superposition of fiber contributions according to a general theory of fi-
brous connective tissue. Concluding remarks relate to open problems in
aorta biomechanics like uncertainty and variability of input information.
Remarks are also made on the admissible degree of complexity in aortic
simulations in the context of such uncertainties.
1
Contents
1 Introduction 3
2 Histology and morphology of the aorta 3

2.1 Extra cellular matrix (ECM) . . . . . . . . . . . . . . . . . . . . 4
2.1.1 Collagen structure . . . . . . . . . . . . . . . . . . . . . . 4
2.1.2 Elastin structure . . . . . . . . . . . . . . . . . . . . . . . 7
2.2 Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3 Mechanical properties and experimental observations 9
4 Constitutive descriptions 11
4.1 Modeling frameworks . . . . . . . . . . . . . . . . . . . . . . . . . 12
4.2 Purely phenomenological descriptions . . . . . . . . . . . . . . . 13
4.3 Histo-mechanical descriptions . . . . . . . . . . . . . . . . . . . . 13
4.4 Damage and failure descriptions . . . . . . . . . . . . . . . . . . . 14
4.5 Growth and Remodeling descriptions . . . . . . . . . . . . . . . . 14
5 Conclusion 15
6 Acknowledgement 16
2
1 Introduction
The aorta is the first arterial segment of the systemic blood circulation, directly
connected to the heart. The aorta is the largest artery in the human body with
a diameter of 3 cm at its origin (ascending aorta), 2.5 cm in the descending
portion (thoracic aorta), and 1.82 cm in the abdomen (abdominal aorta). In
addition to the conduit function, the aorta also accomplishes a buffering func-
tion, i.e. its (visco)-elastic compliance plays a pivotal role in regulating left
ventricular performance, myocardial perfusion and arterial function in the en-
tire cardiovascular system [Nichols et al., 2011]. Consequently, relation between
aortic stiffness and left ventricular hypertrophy, as well as cardiovascular mor-
bidity/mortality in general has been well documented [Laurent et al., 2006]. In
addition to this circulatory implications, the aorta itself is particularly prone to
mechanics-triggered injuries, with formation of aneurysms being the most com-
monly observed aortic pathology. Most interestingly, histopathological changes
of the aortic wall show striking spatial correlation with biomechanical stress.
For example, dilations of the ascending aorta occurs preferentially at the outer
curvature of the vessel, i.e. at the site of maximum axial stress [Gomez et al.,
2009], and blood flow alterations from above-knee amputations causes a five-fold
higher prevalence for abdominal aortic aneurysm development [Vollmar et al.,
1989]. The aorta is also highly vulnerable to aging, and age-related increase in
diameter and stiffness [Länne et al., 1992] are much more pronounced in the
aorta than other vessels. There has, therefore, been enormous motivation to
assess the mechanical properties of the aorta so as to understand cardiovascu-
lar physiology and the mechanisms of cardiovascular disease. Computational
biomechanics may assist reasonably in such investigations. The main challenge,
however, is to relate the complex architecture of the aortic wall to engineer-
ing concepts in order to draw robust conclusions towards aortic wall pathology
development and progress.
2 Histology and morphology of the aorta

A sound histological understanding is imperative for the mechanical charac-
terization of soft biological tissue. Similar to other vessels, extracellular matrix
(ECM) components (elastin, collagen, proteoglycans (PGs), fibronectin, fibrilin,
etc.) ensure the aortic wall’s structural integrity, whereas cells (endothelial
cells, smooth muscle cells (SMC), fibroblasts, myofibroblasts, etc.) maintain its
metabolism. Specifically, the proteins elastin and collagen almost entirely define
the aorta’s passive mechanical properties, while SMCs are responsible for its ac-
tive properties, and, together with fibroblasts, also for the production of ECM
components [McDonald, 2011]. The aorta should always be regarded as dynamic
structure which, within certain physiologic ranges, is able to adapt to functional
needs. The aorta’s geometrical, histological and mechanical properties change
from the ascending aorta towards the abdominal aorta, (see Figure 2), likely to
maintain conditions for optimal mechanical operation [Rachev et al., 2013]. In
3
addition aortic properties and histology change with age [Länne et al., 1992].
Such changes are associated with alterations in chemical composition (decreased
elastin content, increased collagen content, increased levels of metalloproteinase-
2 (MMP2)), as well as in wall histology (thinner, splitted and fraying of Medial
Lamellar Units (MLUs), increased glycation of elastin, increased crosslinking of
collagen), see [Bailey et al., 1998, Nichols et al., 2011, Astrand et al., 2011] and
references therein.
The aorta is composed of intimal, medial and adventitial layers, see Figure 1.
The intima is the innermost layer and comprises primarily of a single layer
of endothelial cells lining the arterial wall. Endothelial cells rest on a thin
basal membrane on top of a subendothelial layer, whose thickness changes with
topography, age and disease.
The media is the middle layer of the artery (see Figure 1) and consists
of a complex three-dimensional network of SMCs, elastin and collagen fibers
and fibrils. These structural components are preferentially aligned along the
circumferential vessel direction [O’Connell et al., 2008, Gasser et al., 2012] and
organized in repeating MLUs of 13-15 µm thickness [Clark and Glagov, 1985,
Dingemans et al., 2000, O’Connell et al., 2008]. The thickness of MLUs is
independent of the radial location in the wall and the number of MLUs increases
with increasing vessel diameter, such that the tension carried by a single MLU
in the normal wall remains constant at about 2±0.4 N/m [Clark and Glagov,
1985]. The media’s layered structure is gradually lost towards the periphery,
and a discrete laminated architecture is hardly present in the abdominal aorta.
The adventitia is the outermost layer of the artery (see Figure 1) and consists
mainly of fibroblasts and fibrocytes and ECM of thick bundles of collagen fibrils.
The adventitia is surrounded by loose connective tissue that anchors the aorta
to its surrounding. Medial and adventitial thicknesses depend strongly on the
physiological function of the blood vessel and its topographical site, see Figure 2.
2.1 Extra cellular matrix (ECM)

The 3D organization of ECM components is vital towards accomplishing proper
physiological aortic functions. The ECM rather than being merely a system of
scaffolding for the surrounding cells, is a mechanical structure that controls the
micro-mechanical and macro-mechanical environments to which vascular tissue
is exposed, i.e. it quantifies the amount of stress and/or strain that is trans-
mitted to the individual cells of vascular tissue and influences cell metabolism
[Carey, 1991]. Specifically, elastin and collagen are dominating ECM vessel wall
components and their organization is schematically illustrated in Figure 1.
2.1.1 Collagen structure

Collagen fibrils of diameters ranging from fifty to a few hundreds of nanometers
are the basic building blocks of fibrous collagenous tissues [Fratzl, 2008], and
their organization into suprafibrilar structures has a large impact on the tissue’s
macroscopic mechanical properties.
4
Collagen fibers are assembled by Elastin fibers are assembled by an amor-
interlinked collagen fibrils of diffe- phous core of cross-linked elastin protein
rent undulations and an outer mantle of undulated and
cross-linked fibrillin
Collagen fibrils are assem- Proteoglycan bridges
bled by interlinked collagen Collagen fibril Elastin core
triple helix molecules
Microfibril
200 nm Cross-link
2 µm
100 nm
The adventitia is formed by thick bund-
les of collagen fibers, fibroblasts and
elastin fibers. Fibers in the adventitia
Elastin sheet Elastin fiber
are highly dispersed in orientations
The media is formed by Medial Lamel-

lar Units (MLU) within which elastin Thick radial strut
fibers, collagen fibers and SMC fibers
are predominanltly aligned along the
circumferential direction
Fibroblast cell
Smooth Muscle Cell (SMC)
Collagen fibrils and fibers
Elastic lamina externa
Endothelial cell 3 µm
Elastin fiber
Elastic lamina interna Elastin is organized in sheets, in rope-like
elastin fibers, and as thick radial struts
5 mm
Figure 1: Histological idealization of the normal aorta. It is composed of three

layers: intima (I), media (M), adventitia (A). The intima is the innermost layer
consisting of a single layer of endothelial cells, a thin basal membrane and a
subendothelial layer. Smooth Muscle Cells (SMCs), elastin and collagen are
key mechanical constituents in the media and are arranged in a number (up to
60) of 13-15 µm thick Medial Lamellar Units (MLUs). (In the image only three
MLUs are shown). In the adventitia the primary constituents are collagen fibers
and fibroblasts. Collagen fibers with a thickness in the range of micrometers
are assembled by collagen fibrils (50 to 300 nm thick) of different undulations.
Load transition between collagen fibrils is maintained by Proteoglycan (PG)
bridges. Elastin fibers with a thickness of hundreds of nanometers are formed
by an amorphous core of highly cross-linked elastin protein that is encapsulated
by 5nm thick microfibrils. Elastin fibers are organized in thin concentric elastic
sheets, in a rope-like interlamellar elastin fibers, and as thick radial struts.
5
(a)
18.0
Vessle Layer Thickness (mm)
Outer Vessle Diameter (mm)

2.0
Medial 12.0
layer thickness
Outer vessel
diameter
1.0 6.0
Adventitial layer
3.0
thickness
0.0
Asc. Thor. Arch Desc. Thor. Abdominal
(b)
80 Adventitial collagen
Relative area density (%)
60
40
Medial elastin
20 Medial collagen
Adventitial elastin
0
Asc. Thor. Arch Desc. Thor. Abdominal
Figure 2: Variation of geometrical properties and histological composition of the

porcine aorta [Sokolis, 2007]. (a) Change of outer aortic diameter and thickness
of medial and adventitial layers. Intimal layer thickness covers less than 1%
of the total wall thickness. (b) Relative area density of elastin and collagen
in medial and adventitial layers. The relative area density represents the area
covered by a constituent in histological stains. Asc.Thor. - Ascending thoracic
aorta; Arch. - Aortic arch; Desc.Thor. - Descending thoracic aorta; Abdominal
- Abdominal aorta.
Within the MLU, i.e. between the elastic lamellae of the media, collagen
fibrils or bundles of fibrils (24±15 fibers per bundle) run in parallel closely
enveloping the SMCs [O’Connell et al., 2008]. Consequently, collagen fibers
6
are not woven together but aligned in parallel (like in a tendon or ligament),
probably to better cope with mechanical load [O’Connell et al., 2008].
Collagen gives stiffness, strength and toughness to the vascular wall. Ear-
lier observations indicated that the collagen-rich abdominal aorta was stiffer
than the collagen-poor thoracic aorta [Bergel, 1961, Langewouters et al., 1984]
and later regional variations of aortic properties were specifically documented,
see [Sokolis, 2007]. Apart from the amount of collagen in the wall, its spatial
orientation [Fratzl, 2008] (including the spread in orientations [Gasser et al.,
2006]) also strongly influences macroscopic mechanical properties. At physio-
logical load only 6% to 7% of collagen fibers are engaged [Armentano et al.,
1991, Greenwald et al., 1997].
Collagen fibrils seem to be interlinked by Proteoglycan (PG) bridges [Scott,
2003, 2008] to provide interfibrillar load transition. Specifically, small PGs,
such as decorin, bind noncovalently but specifically to collagen fibrils and cross-
link adjacent collagen fibrils at about 60 nm intervals [Scott, 2003]. Reversible
deformability of the PG bridges is crucial to serve as shape-maintaining modules
[Scott, 2003] and, fast and slow deformation mechanisms have been identified.
The fast (elastic) deformation is supported by the sudden extension of about
10% of the L-iduronate (an elastic sugar) at a critical load of about 200 pN
[Haverkamp et al., 2005]. The slow (viscous) deformation is based on a sliding
filament mechanism of the twofold helix of the glycan [Scott, 2003], and may
explain the large portion of macroscopic visco-elasticity of collagen. PG-based
cross-linking is supported by numerous experimental studies showing that PGs
play a direct role in inter-fibril load sharing [Liao and Vesely, 2007, Robinson
et al., 2005, Scott, 2003, Sasaki and Odajima, 1996], and has been verified
through theoretical investigations [Fessel and Snedeker, 2011, Redaelli et al.,
2003, Vesentini et al., 2005]. However, the biomechanical role of PGs is still
somewhat uncertain, and some data indicates minimal, if any, PG contribution
to the tensile properties of the tissue [Fessel and Snedeker, 2011, Rigozzi et al.,
2009, 2010].
Collagen is in a continuous state of deposition and degradation at a normal
half-life time of 60-70 days [Nissen et al., 1978]. Physiological maintenance of
the collagen structure relies on a delicate (coupled) balance between degrada-
tion (mainly through MMPs) and synthesis by cells like SMCs, fibroblasts and
myofibroblasts, [Nichols et al., 2011].
2.1.2 Elastin structure

Elastin functions in partnership with collagen. Elastin mainly determines the
mechanical properties of arterial tissue at low strain levels [Roach and Burton,
1957] and recoils the tissue during each pulse cycle. In the vessel wall, elastin is
predominantly seen in the media, see Figure 2(b). Specifically, it is organized as
thin concentric elastin sheets with a fibrous surface which encapsulate the MLU
(71%; about 1 to 2.2 µm thick), in a rope-like interlamellar elastin fibers (27%;
about 100nm to 500nm thick), and as thick radial struts (2%; about 1.5µm
thick) [O’Connell et al., 2008, Dingemans et al., 2000, Berry and Greenwald,
7
1976]. The elastin lamellae are perforated and gusseted by elastin fibers. Mi-
croscopy studies also indicate that elastin is made up of repeating self-similar
structures at many length-scales [Tamburro et al., 1995]. Elastin fibers are about
100nm thick and composed of two significant components; 90% of which is an
amorphous core of highly cross-linked elastin protein and the remaining 10% is
a fibrillar mantle of about 5 nm thick microfibrils [R. Ross and Bornstein, 1969,
Cleary, 1987].
Elastin is synthesized and secreted by vascular SMCs and fibroblasts, a pro-
cess that normally stops soon after puberty once the body reaches maturity.
Although the dense lysyl cross linking makes elastin fibrils extremely insoluble
and stable (half-life times of tens of years [Alberts et al., 1994]), elastin may be
degraded by selective MMPs, collectively known as elastases. Elastases cause
disruption of elastin fiber integrity and subsequently diminishes mechanical tis-
sue properties. Elastin is a critical autocrine factor that maintains vascular
homeostasis through a combination of biomechanical support and biologic sig-
naling, see [Bäck et al., 2013] and references therein. While elastin degradation
is related to several diseases (atherosclerosis, Marfan syndrome, Cutis laxa, etc.
), it is also important for many physiological processes such as growth, wound
healing, pregnancy and tissue remodeling [Werb et al., 1982]. Consequently, the
proteolytic degradation of elastin may have important consequences for nor-
mal elastogenesis and repair processes [Vrhovski and Weiss, 1998]. Repair of
protease-damaged elastin can occur but does not appear to produce elastin of
the same quality as when originally laid down during development, i.e. primary
vascular growth [Soskel and B.Sandberg, 1987].
Elastin and rubber show some mechanical similarities. For example, both
are entropic elastic and go through a glassy transition. However, elastin’s hy-
drophobic interactions are a determining factor in its elasticity, such that elastin
is only elastic when swollen in water, see [Vrhovski and Weiss, 1998] and refer-
ences therein.
2.2 Cells
Cells like endothelial cells, SMCs, fibroblasts, etc. in the aorta sense and respond
to mechanical loads, allowing the aorta to undergo many changes during normal
development, ageing, in response to disease or implanted devices, etc.
Endothelial cells are constantly exposed to wall shear stress (WSS) and pro-
vide an anti-thrombogenic and low-resistance lining between the blood and aor-
tic tissue. WSS experienced by the endothelial cells is associated with changes
in gene expression patterns through positive and negative WSS responsive ele-
ments in their promoter regions [Chen et al., 2003]. In the aneurysmatic aorta
the frequently seen intra-luminal thrombus layer [Hans et al., 2005] shields en-
dothelial cells from blood flow and, if not die out, they likely loose their blood
flow regulatory role.
Elongated vascular SMCs are layered between elastic lamellae, i.e within the
MLU. They are aligned with the circumferential direction and at a radial tilt of
about 20 degrees [O’Connell et al., 2008, Fujiwara and Uehara, 1992]. In their
8
differentiated/contractile phenotype vascular SMCs serve as contractile unit in
the vessel wall and actively influence aortic diameter [Milewicz et al., 2010]. In
addition, in their dedifferentiated/synthetic phenotype vascular SMCs respond
to cyclic stretch, as well as to mediators that are convected through the aortic
wall with the transmural interstitial flow [Milewicz et al., 2010]. The effects of
cyclic stretching of vascular SMCs on collagen production were described almost
40 years ago [Leung et al., 1976], where increased strain up-regulates MMPs in
vascular SMCs [Grote et al., 2003], such that increased mechanical strain may
lead to enhanced ECM degradation. In addition to these direct vascular SMC
response, endothelium-derived vasoactive factors, released in response to WSS
for example, act on the aortic SMCs, see [Bäck et al., 2013] and references
therein.
Fibroblast cells are tightly anchored to collagen fibers and, together with
SMCs (at dedifferentiated/synthetic phenotype) and MMPs, control the deli-
cate balance between synthesis and degradation of collagen. Mature fibroblasts
respond to mechanical strain or stress and adjust their expression and synthesis
of collagen molecules [Grote et al., 2003, Bishop and Lindahl, 1999], perhaps
similar to cardiac fibroblasts, where members of the Mitogen-activated pro-
tein (MAP) kinase family upregulate procollagen gene expression in response to
cyclic mechanical load [Papakrivopoulou et al., 2004].
3 Mechanical properties and experimental ob-

servations
The pressure-diameter property (compliance) of the aorta is of critical impor-
tance to the entire cardiovascular system and determines the non-linearity of its
pressure-flow relationship [Fung, 1990]. The aorta contributes almost the entire
capacity of the cardiovascular system, i.e. defines its Windkessel properties, see
[Westerhof et al., 2009] and references therein. The aortic volume compliance
(C = ∆V /∆p) is constant over a wide range of pressures, and the thoracic aorta
alone contributes 85% to the aortic compliance [Guo and Kassab, 2003].
The aortic wall can be regarded as a mixture of solid components (elastin,
collagen, SMCs, PGs, etc) and water, much of which is not particularly mobile
but bound to PGs, elastin, and the like. While the radial convection of fluid
(which is established due to pressure gradient between the arterial circulation
and the interstitial pressure in the adventitia) is essential for aorta physiology
[Bäck et al., 2013], for many mechanical problems the aortic wall can be regarded
as an incompressible homogenized solid; in-vivo the volumetric strain is three
orders of magnitude smaller than the circumferential strain [Carew et al., 1968].
The normal (non-calcified) aorta is highly deformable and exhibits a non-
linear [Roy, 1880–82] stress versus strain response with a typical stiffening at
around the physiological strain level. The aorta’s circumferential stiffness is
highest at the level of the diaphragm [Tanaka and Fung, 1974, Guo and Kassab,
2003], increases with age and might also be higher in males than in females
9
[Sonesson et al., 1993]. The thick and collagen-rich adventitial layer (see Fig-
ure 2) of the abdominal aorta leads to the observed increase of stiffness of the
abdominal aorta when compared to the thoracic aorta.
Vascular tissue characterization after selective digestion of elastin or colla-
gen [Roach and Burton, 1957, Dobrin and Canfield, 1984, Marsh et al., 2004,
Gundiah et al., 2013] contributed considerably to our current understanding of
vessel wall mechanics. Experimental data suggest that the vessel wall stiffens
(at physiological deformations) in response to the recruitment of the embed-
ded wavy collagen fibrils [Roach and Burton, 1957, Wolinsky and Glagov, 1964,
Samila and Carter, 1981], a mechanism that in turn explains the non-linear elas-
ticity of the aorta. Such a collagen fiber engagement mechanism also explains
the anisotropic properties of the aorta [Patel et al., 1969, Vande Geest et al.,
2006b] with a higher stiffness along the circumferential direction; direction along
which more collagen fibers are oriented [O’Connell et al., 2008, Gasser et al.,
2012]. Analyzing in-vivo pressure diameter properties of the abdominal aorta
revealed that the load-bearing fraction of collagen between diastole and systole
oscillates between 10% and 30%, respectively [Astrand et al., 2011].
The constant turnover of wall constituents at the aorta’s in-vivo configura-
tion explains residual stresses in its load-free configuration. Residual stresses in
the arteries have been known for at least half a century [Bergel, 1961] and their
biomechanical consequences are well discussed in the literature [Choung and
Fung, 1986, Fung, 1991, Rachev and Greenwald, 2003, Vaishnav and Vossoughi,
1987]. Specifically, it is reported that both, circumferential [Choung and Fung,
1986, Vaishnav and Vossoughi, 1987] and longitudinal [Vossoughi, 1992] strips
change their curvature when excised from a load-free artery, i.e. residual stresses
in the vascular wall are clearly multi-dimensional. Neglecting residual stresses
in the load-free configuration can be a severe limitation [de Putter et al., 2007,
Lu et al., 2007] and for purely passive simulations typically leads to consider-
able stress gradients across the wall thickness. Such a wall stress field is non
physiological, i.e. in contradiction to the uniform stress hypothesis [Fung, 1991].
In humans, the aorta is axially pre-stretched at 5% [Astrand et al., 2011], a
property that, however, changes with age [Horny et al., 2013] and between the
different aortic segments [Guo and Kassab, 2003]. Experimental data indicated
that at in-vivo pre-stretch the axial force acting on the vessel remains indepen-
dent from the inflation pressure [Weizsäcker et al., 1983], i.e. inside the body
pulsatile axial strain is prevented.
In-vitro testing of arterial tissue typically displays pronounced stress soft-
ening under the first few cycles of loading until the tissue is preconditioned
and a stable cyclic response is observed. Even when preconditioned, the aortic
wall shows typical strain rate dependency like creep, relaxation and dissipation
under cyclic loading. Most interestingly, the dissipation during cyclic load-
ing over a frequency range of five orders of magnitude does not change by a
factor of more than two [Tanaka and Fung, 1974]. Exposing vascular tissue
to supra-physiological mechanical stresses rearranges the tissues microstructure
through irreversible deformations; damage-related effects [Emery et al., 1997a,
Oktay et al., 1991] and plasticity-related effects [Oktay et al., 1991, Salunke
10
and Topoleski, 1997] have been documented. Probably there is some correla-
tion between the mechanisms of pre-conditioning and inelastic phenomena when
exceeding the physiological loading.
Due to its high clinical relevance, the aneurysmatic infrarenal aorta has been
studied extensively. The biomechanical properties of the infrarenal aneurysm’s
wall differ considerably from the properties of the normal aorta. Specifically, the
stress strain law of the aneurysmatic wall is more nonlinear, the wall deforms
less [Vande Geest et al., 2006b] and has a lower strength when compared to
the normal aortic wall strength (descending thoracic: 1.95 ± 0.6 MPa [Adham
et al., 1996]; the midthoracic: 1.470 ± 0.91 MPa [Mohan and Melvin, 1982];
abdominal aorta: 1.21 ± 0.33 MPa [Vorp et al., 1996]; 1.710 ± 0.14 MPa [Vorp
et al., 2003]). Table 1 presents a review of reported thickness and strength
data of the infrarenal aortic aneurysm wall. The data indicates a remarkable
negative correlation (Pearson’s correlation coefficient = -0.71) between thickness
and strength, which has also been reported elsewhere, see for example [Reeps
et al., 2013, Forsell et al., 2014].
SMC at the differentiated/contractile phenotype regulate the aortic diame-
ter and stiffness. Specifically, contractile cell fibers span the vascular SMC cell
body to generate force against the ECM [Alberts et al., 1994]. The level of vas-
cular SMC activation or basal tone changes in response to biomechanical stimuli
such as flow [Davies, 1995] or pressure [Fridez et al., 2001], hormonal stimuli,
neural stimuli, and drugs. Vascular SMC in its normal tone state appears to be
sensitive to both circumferential and longitudinal stretching of the vessel wall,
see [Zulliger et al., 2004b] and references therein.
The normal vessel seems to follow the concept of homeostasis, i.e. it adapts
to changes in the mechanical environment such that target mechanical proper-
ties are kept relatively constant. Specifically, target values for WSS [Guzman
et al., 1997, Castier et al., 2005], circumferential wall stress [Wolinsky, 1971,
Matsumoto and Hayashi, 1996] and axial stretch [Gleason et al., 2007] have
been shown to be regained after alterations. Normal vessel remodeling is dimin-
ished in the aneurysmatic aorta and the wall in larger aneurysm seems to lose
its ability to respond to mechanical stress [Martufi et al., 2016, Nchimi et al.,
2014]. In addition, during aneurysm development wall thickness remains rela-
tively constant, such that wall stress increases proportionally with the size of
the aneurysm [Gasser et al., 2014], i.e. is not kept at its homeostatic level.
4 Constitutive descriptions
Constitutive modeling of vascular tissue is an active field of research and nu-
merous descriptions with application to the aorta have been reported. While
purely phenomenological approaches can successfully fit experimental data, such
models show limited robustness for predictions beyond the strain range within
which model parameters have been identified, and they cannot allocate stress or
strain to the different histological constituents in the vascular wall. Structural
constitutive descriptions overcome such limitations and integrate histological
11
and mechanical information of the arterial wall, which in turn is not only more
robust but also helps to understand load carrying mechanisms in the vessel wall.
Clearly, modeling assumptions need to fit the objective of the particular
simulation [Sargent, 2011], and for most applications the aortic wall can be
regarded as a single phase incompressible solid. Even the highly porous intra-
luminal thrombus [Adolph et al., 1997, Gasser et al., 2010] can be modeled as a
homogenized solid [Polzer et al., 2012] for a wall stress-based aneurysm rupture
risk assessment, for example. However, the suitability of all applied model-
ing assumptions needs to be carefully validated, and more complex frames like
poro-elasticity [Simon and Gaballa, 1988] for example, can be motivated.
4.1 Modeling frameworks

Hyperelasticity for incompressible solids is a popular modeling framework to
derive the Cauchy stress
∂ψ(C) T
σ = 2F F − pI (1)
∂C
of aortic tissue from the strain energy density ψ(C) in reference volume. Here,
tissue deformation is determined by the right Cauchy-Green strain C = F TF,
which is a function of the deformation gradient F. The hydrostatic pressure p
acts on the identity I and serves as a Lagrange parameter to enforce incompress-
ibility. All constitutive information (mechanical and histological) is captured by
a particular form of the strain energy function ψ, and Table 2 lists some models
for aortic tissues.
The stress in the aortic wall can also be expressed according to the general
theory of fibrous connective tissue [Lanir, 1983]. Such descriptions are also
denoted as angular integration models and allow integrating fibers of dispersed
ordination and undulation. Specifically, an orientation density function ρ(ϕ, θ)
reflects the orientation of fibers in the reference configuration with respect to
elevation ϕ and azimuthal θ angles. The superposition of such fibers determines
the tissue’s Cauchy stress
∫π/2 ∫π/2
2
σ= ρ(ϕ, θ)σ(λ)dev(m ⊗ m) cos ϕdϕdθ − pI , (2)
π
ϕ=0 θ=0
where m = FM denotes the push forward of the referential fiber direction M.

Here, σ(λ) expresses the Cauchy stress in a fiber as a function of the fiber stretch
λ, i.e. reflects a constitutive model on the fiber level, and dev(•) = (•)−tr(•)I/3
denotes the spatial deviator operator.
Model parameters, i.e. constitutive parameters appearing in ψ of eq.(1) as
well as in ρ and σ of eq.(2) are identified from experimental data by least-
square optimization, for example. The uniform stress hypothesis [Fung, 1991]
and other plausible assumptions [Weizsäcker et al., 1983] have been used as con-
straints in parameter estimation [Takamizawa and Hayashi, 1987, Rachev et al.,
12
1996, Taber and Humphrey, 2001, Stålhand and Klarbring, 2005] to improve
the reliability of the estimated model parameters.
4.2 Purely phenomenological descriptions

Due to some similarities between vascular tissue and rubber (like entropic elas-
ticity), models that originally have been proposed for rubber are also frequently
used for the aorta, see Table 2(a). In contrast, models that have especially been
developed for vascular tissue include exponential terms in the strain energy ψ
[Demiray, 1972, Fung et al., 1979] and even consider anisotropy [Vaishnav et al.,
1972, Chuong and Fung, 1983, Takamizawa and Hayashi, 1987, Horgan and
Saccomandi, 2003]. For such models, the strain energy is typically expressed
as a function of the components of the Green-Lagrange strain E = (C − I)/2
within the local cylindrical coordinate system, i.e. ψ(Eij ) for i, j = r, ϑ, z
with r, ϑ, z denoting the radial, circumferential and axial vessel directions, re-
spectively. Such models have also been enriched by techniques to estimate the
residual strain field from the uniform stress hypothesis [Polzer et al., 2013], or to
back-calculate the zero-load configuration from inflated geometries [de Putter
et al., 2007, Riveros et al., 2013].
4.3 Histo-mechanical descriptions

Motivated by the results from selective digestion of elastin and collagen [Roach
and Burton, 1957, Dobrin and Canfield, 1984], constitutive models started to
regard the vessel wall as a mixture (composition) of collagen, elastin and SMCs
[Oka and Azuma, 1970, Holzapfel et al., 2000, Humphrey and Rajagopal, 2002,
Sokolis et al., 2006]. Nowadays, most studies assume that elastin and collagen
are major independent determinants (each of which is reflected by an additive
strain energy contribution, see examples in Table 2) of the mechanical properties
of the aortic wall at low and high stresses, respectively.
In addition to composition-based models, the actual load carrying of colla-
gen fibers attracted much attention. Almost 40 years ago a tissue model based
on aligned wavy collagen fibers that engage during loading [Decraemer et al.,
1980] has been reported, and later very similar ideas have been adopted to the
vessel wall [Wuyts et al., 1995, Zulliger et al., 2004a, Martufi and Gasser, 2011],
see Table 3). Alternatively, the strong stiffening effect of the collagen fibers dur-
ing stretching was phenomenologically integrated in the strain energy function
by an exponential expression [Holzapfel et al., 2000] (HGO model) or a 6th-
order polynomial term [Basciano and Kleinstreuer, 2009]. Collagen and elastin
fiber orientations in the vessel wall are dispersed [Schriefl et al., 2012, Polzer
et al., 2015, Thunes et al., 2016]. Specifically, the collagen in the adventitia
of normal [Finlay et al., 1995] and aneurysmatic [Gasser et al., 2012] aortas is
highly dispersed, and Table 4 summarizes models to express such dispersions.
Consequently, the basic assumption of two (or more) families of parallel aligned
collagen fibers seems unrealistic [Polzer et al., 2015] and the GOH model pro-
posed an efficient way of integrating the dispersion of fiber orientations in the
13
strain energy function [Gasser et al., 2006]. The GOH model considers all col-
lagen fibers within the i-th (dispersed) family of fibers being strained homoge-
nously at Ei = Hi : C − 1 with Hi denoting a general structural tensor. This
assumption seems appropriate for the aorta at physiological loading, where ho-
mogenously stressed collagen is continuously deposited. However, for other load
cases (prior to tissue failure, during automobile accidents, etc.) collagen fibers
are likely stressed inhomogenously, and the more general framework according
to eq.(2) is motivated. Apart from the above described homogenization ap-
proaches, Representative Volume Element (RVE) models have been reported to
integrate histological and mechanical properties of the MLU composites [Thunes
et al., 2016].
On top of passive stresses, SMC contraction acts along the vessel’s circum-
ference and influences vessel wall stress. Constitutive models accounted either
directly [Zulliger et al., 2004b], or indirectly through the calcium concentration
[Sharifimajd and Stålhand, 2014], for (active) SMC stress. Interestingly, con-
sidering active stress from SMCs seems, in addition to residual strain in the
load-free configuration, reducing the transmural stress gradient at physiological
loading [Rachev and Hayashi, 1999].
4.4 Damage and failure descriptions

Exposing biological soft tissue to supraphysiological mechanical stresses rear-
ranges vascular tissue’s microstructure through irreversible deformations. Specif-
ically, damage-related effects [Emery et al., 1997a,b, Oktay et al., 1991] and
plasticity-related effects [Oktay et al., 1991, Salunke and Topoleski, 1997] have
been proposed, which in turn triggered the development of models that account
for damage [Hokanson and Yazdani, 1997, Balzani et al., 2006, Volokh and
Vorp, 2008, Calvo et al., 2009, Marini et al., 2011, Noble et al., 2016], plasticity
[Tanaka and Yamada, 1990, Gasser and Holzapfel, 2002] and fracture [Ionescu
et al., 2006, Gasser and Holzapfel, 2006, 2007, Ferrara and Pandolfi, 2008, Forsell
and Gasser, 2011]. Most commonly a macroscopic (single scale) framework was
followed, which, however, fails to describe the experimentally reported [Quinn
and Winkelstein, 2008, Knörzer et al., 1986] localized irreversible deformation
of individual collagen fibers. In contrast, irreversible collagen fiber deformation
(related to PG-based deformation mechanisms) has been integrated in eq.(2) to
model aneurysm wall failure [Gasser, 2011].
4.5 Growth and Remodeling descriptions

The aorta responds to mechanical stimuli, which is a necessity to locally alter its
mechanical properties towards approaching conditions for optimal mechanical
operation [Rachev et al., 2013]. Modeling vascular adaptation (growth and
remodeling) is an active field of research [Humphrey and Rajagopal, 2002], much
of which is related to aneurysm development and progression [Volokh and Vorp,
2008, Watton and Hill, 2009, Kroon and Holzapfel, 2009, Zeinali-Davarani and
Baek, 2012, Wilson et al., 2012, Martufi and Gasser, 2012]. Most of these models
14
are characterized by a high degree of phenomenology, and all of them are poorly
validated. Consequently, significant further development is required to provide
robust predictions that could augment clinical decisions, for example.
5 Conclusion
The aorta’s biomechanical properties are not only related to aortic patholo-
gies but also critical to the biomechanics of the entire cardiovascular system.
The aortic wall is a dynamic structure able to maintain conditions for optimal
mechanical operation by continuous turnover of its internal structure. Numer-
ous constitutive description for aortic tissues at different levels of details have
been proposed. Specifically, histo-mechanical approaches are able to examine
local micro-architectural features, which in turn constrains internal load carry-
ing mechanisms, and provide more robust predictions when compared to purely
phenomenological descriptions. In contrast, such histo-mechanical models can
be quite complex, involving many structural and mechanical parameters, which
need to be carefully and consistently identified.
Naturally, every model involves making modeling assumptions and reflects
the real object or process always only up to a certain degree of completeness
(”Everything should be made as simple as possible, but no simpler”; quote at-
tributed to A. Einstein, see http://quoteinvestigator.com/2011/05/13/einstein-
simple/#more-2363), and a model should be validated to the degree needed for
the model’s intended purpose or application [Sargent, 2011]. Consequently, a
good model will only include modeling details that improve the intended simula-
tion objective, and, even if in contradiction to our current knowledge about the
actual biomechanical problem, disregard all the other information. For exam-
ple, the required degree of complexity of the aortic wall model (isotropic versus
anisotropic modeling; single phase versus multiphase modeling; constant wall
thickness versus variable wall thickness; etc.) used to provide clinical diagnostic
information can only be evaluated in relation to the model’s implication on the
clinical outcome - a complex model does not necessarily give better diagnostic
information.
Despite encouraging progress in vascular tissue biomechanics, the variability
of biomechanical predictions due to uncertainty of input information remains a
challenging limitation. Specifically, for clinical applications key input informa-
tion like detailed geometrical features and the local biomechanical properties
of aortic wall tissue often remains unknown. Owing to this lack of input in-
formation, homogeneous mean population input information is often used, and
the extent to which this simplification influences the value of model predictions
remains to be explored for each individual application. In view of these key
limitations, many constitutive models reported in the literature seem overdone.
Probabilistic approaches seem to be a promising way to deal with input uncer-
tainty of aorta biomechanics, and such approaches have been reported recently
[Biehler et al., 2014, Polzer et al., 2015].
Even under well-defined laboratory conditions, the in-vitro experimental
15
characterization of aortic wall properties show huge variability and the esti-
mated tissue properties usually vary at least by one order of magnitude. While
the detailed causes of this variability remain largely unknown, several influen-
tial parameters have already been identified. For example it seems that Chronic
Obstructive Pulmonary Disease (COPD) [Forsell et al., 2012], bicuspid aortic
valve anatomy [C.Y. Shim, 2011, Forsell et al., 2014], Marfan syndrome [Marque
et al., 2001], diabetes mellitus [Maier et al., 2012], as well as the administra-
tion of drugs (like beta blocker and Angiotensin-Converting-Enzyme (ACE) in-
hibitors [Maier et al., 2012]) alter biomechanical vessel wall properties. Further
exploring such influential factors may help to improve the reliability of aorta
biomechanics.
6 Acknowledgement
The author would like to thank Andrii Grytsan and Prashanth Srinivasa from
KTH Royal Institute of Technology, Stockholm for the valuable feed-back on
the manuscript.
References
M. Adham, J. P. Gournier, J. P. Favre, E. De La Roche, C. Ducerf, J. Baulieux,
X. Barral, and M. Pouyet. Mechanical characteristics of fresh and frozen
human descending thoracic aorta. J. Surg. Res., 64:32–34, 1996.
R. Adolph, D. A. Vorp, D. L. Steed, M. W. Webster, M. V. Kameneva, and

S. C. Watkins. Cellular content and permeability of intraluminal thrombus
in Abdominal Aortic Aneurysm. J. Vasc. Surg., 25:916–926, 1997.
B. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, and J.D. Watson. Molecular
biology of the cell. Garland Publishing, New York, 1994.
R. L. Armentano, J. Levenson, J. G. Barra, E. I. Fischer, G. J. Breitbart, R. H.
Pichel, and A. Simon. Assessment of elastin and collagen contribution to
aortic elasticity in conscious dogs. Am. J. Physiol., 260:H1870–H1877, 1991.
H. Astrand, J. Stålhand, J. Karlsson, M. Karlsson, and B. Sonesson Band T.

Länne. In vivo estimation of the contribution of elastin and collagen to the
mechanical properties in the human abdominal aorta: effect of age and sex.
J. Appl. Physiol., 110:176–187, 2011.
S. Baek, R. Gleason, K. R. Rajagopal, and J. D. Humphrey. Theory of small on

large: Potential utility in computations of fluid-solid interactions in arteries.
Comput. Meth. Appl. Mech. Eng., 196:3070–3078, 2009.
A.J. Bailey, R.G. Paul, and L. Knott. Mechanism of maturation and ageing of
collagen. Mech. Ageing Dev., 106:1–56, 1998.
16
D. Balzani, J. Schröder, and D. Gross. Simulation of discontinuous damage in-
corporating residual stresses in circumferentially overstretched atherosclerotic
arteries. Acta Biomaterialia, 2:609–618, 2006.
C.A. Basciano and C. Kleinstreuer. Invariant-based anisotropic constitutive

models of the healthy and aneurysmal abdominal aortic wall. J. Biomech.
Eng., 131:021009 (11 pages), 2009.
D. H. Bergel. The static elastic properties of the arterial wall. J. Physiol., 156:
445–457, 1961.
C. L. Berry and S. E. Greenwald. Effect of hypertension on the static mechanical

properties and chemical composition of the rat aorta. Cardiovasc. Res., 10:
437–451, 1976.
J. Biehler, M.W. Gee, and W.A. Wall. Towards efficient uncertainty quantifica-
tion in complex and large scale biomechanical problems based on a bayesian
multi fidelity scheme. Biomech. Model. Mechanobio., 14:489513, 2014.
C. Bingham. An antipodally symmetric distribution on the sphere. Ann. Statist.,

2:1201–1225, 1974.
J. E. Bishop and G. Lindahl. Regulation of cardiovascular collagen synthesis by

mechanical load. Cardiovasc. Res., 42:27–44, 1999.
B. Calvo, E. Peña, P. Martins, T. Mascarenhas, M Doblaré, R. M. Natal Jorge,

and A. Ferreira. On modelling damage process in vaginal tissue. 42:642–651,
2009.
T. E. Carew, R. N. Vaishnav, and D. J. Patel. Compressibility of the arterial
wall. Circ. Res., 23:61–68, 1968.
D. Carey. Control of growth and differentiation of vascular cells by extracellular
matrix proteins. Annu. Rev. Physiol., 53:161–177, 1991.
Y. Castier, R.P. Brandes, G. Leseche, A. Tedgui, and S. Lehoux. p47phox-
dependent NADPH oxidase regulates flow-induced vascular remodeling. Circ.
Res., 97:533–540, 2005.
S. Celi and S. Berti. Biomechanics and fe modelling of aneurysm: Review and
advances in computational models. In Y. Murai, editor, Aneurysm, chapter 1.
InTech, 2012.
X.-L. Chen, S. E. Varner, A. S. Rao, J. Y. Grey, S. Thomas, C. K. Cook, M. A.

Wasserman, R. M. Medford, A. K. Jaiswal, and C. Kunsch. Laminar flow
induction of antioxidant response element-mediated genes in endothelial cells.
a novel anti-inflammatory mechanism. J. Bio. Chem., 278:703–711, 2003.
H. S. Choi and R. P. Vito. Two-dimensional stress-strain relationship for canine

pericardium. J. Biomech. Eng., 112:153–159, 1990.
17
C. J. Choung and Y. C. Fung. Residual stress in arteries. In G. W. Schmid-
Schoenbein, S. L. Woo, and B. W. Zweifach, editors, Frontiers in Biomechan-
ics, pages 117–129. 1986.
C. J. Chuong and Y. C. Fung. Three-dimensional stress distribution in arteries.

J. Biomech. Eng., 105:268–274, 1983.
J. M. Clark and S. Glagov. Transmural organization of the arterial media: The
lamellar unit revisited. Arteriosclerosis, 5:19–34, 1985.
E. G. Cleary. The microfibrillar component of the elastic fibers, in Connective
tissue disease. Molecular pathology of the extracellular matrix. Dekker, New
York, 1987.
W.-I. Yang M.-K. Kang S. Park J.-W. Ha Y. Jang N. Chung C.Y. Shim, I.J. Cho.
Central aortic stiffness and its association with ascending aorta dilation in
subjects with a bicuspid aortic valve. J. Am. Soc. Echoradiogr., 24:847–852,
2011.
PF Davies. Flow-mediated endothelial mechanotransduction. Physiol. Rev., 75:

519–560, 1995.
W. F. Decraemer, M. A. Maes, and V. J. Vanhuyse. An elastic stress-strain

relation for soft biological tissues based on a structural model. J. Biomech.,
13:463–468, 1980.
H. Demiray. A note on the elasticity of soft biological tissues. J. Biomech., 5:
309–311, 1972.
H. Demiray. Large deformation analysis of some soft biological tissues. J.
Biomech. Eng., 103:73–78, 1981.
K. P. Dingemans, P. Teeling, J. H. Lagendijk, and A. E. Becker. Extracellu-
lar matrix of the human aortic media: An ultrastructural histochemical and
immunohistochemical study of the adult aortic media. Anat. Rec., 258:1–14,
2000.
P. B. Dobrin and T. R. Canfield. Elastase, collagenase, and the biaxial elastic

properties of dog carotid artery. Am. J. Physiol., 247:H124–H131, 1984.
J. L. Emery, J. H. Omens, and A. D. McCulloch. Strain softening in rat left

ventricular myocardium. J. Biomech. Eng., 119:6–12, 1997a.
J. L. Emery, J. H. Omens, and A. D. McCulloch. Biaxial mechanics of the

passively overstretched left ventricle. Am. J. Physiol., 272:H2299–H2305,
1997b.
A. Ferrara and A. Pandolfi. Numerical modeling of fracture in human arteries.
Comput. Meth. Biomech. Biomed. Eng., 11:553–567, 2008.
18
J. Ferruzzi, D. A. Vorp, and J. D. Humphrey. On constitutive descriptors of the
biaxial mechanical behaviour of human abdominal aorta and aneurysms. J.
R. Soc. Interface, 8:435–540, 2010.
G. Fessel and J. G. Snedeker. Equivalent stiffness after glycosaminoglycan de-

pletion in tendon–an ultra-structural finite element model and corresponding
experiments. J. Theor. Biol., 268:77–83, 2011.
H. M. Finlay, L. McCullough, and P. B. Canham. Three-dimensional collagen

organization of human brain arteries at different transmural pressures. J.
Vasc. Res., 32:301–312, 1995.
C. Forsell and T. C. Gasser. Numerical simulation of the failure of ventricular
tissue due to deep penetration: The impact of constitutive properties. J.
Biomech., 44:45–51, 2011.
C. Forsell, T. C. Gasser, J. Swedenborg, and J. Roy. The quasi-static

failure properties of the abdominal aortic aneurysm wall estimated by
a mixed experimental-numerical approach. Ann. Biomed. Eng., 11:
DOI:10.1007/s10439–012–0712–3, 2012.
C. Forsell, H. M. Bjrck, P. Eriksson, A. Franco-Cereceda, and T. C. Gasser.

Biomechanical properties of the thoracic aneurysmal wall; differences between
bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients. Ann.
Thorac Surg., 98:65–71, 2014.
P. Fratzl, editor. Collagen - Structure and Mechanics. Springer-Verlag, New

York, 2008.
P. Fridez, A. Makino, H. Miyazaki, J. J. Meister, K. Hayashi, and N. Ster-

giopulos. Short-term biomechanical adaptation of the rat carotid to acute
hypertention: contribution of smooth muscle. Ann. Biomed. Eng., 29:26–34,
2001.
T. Fujiwara and Y. Uehara. The cytoarchitecture of the medial layer in rat

thoracic aorta: a scanning electron-microscopic study. Cell Tissue Res., 270:
165–172, 1992.
Y. C. Fung. Biomechanics. Motion, Flow, Stress, and Growth. Springer-Verlag,

New York, 1990.
Y. C. Fung. What are the residual stresses doing in our blood vessels? Ann.
Biomed. Eng., 19:237–249, 1991.
Y. C. Fung, K. Fronek, and P. Patitucci. Pseudoelasticity of arteries and the

choice of its mathematical expression. Am. J. Physiol., 237:H620–H631, 1979.
T. C. Gasser. An irreversible constitutive model for fibrous soft biological tis-

sue: A 3d microfiber approach with demonstrative application to Abdominal
Aortic Aneurysms. Acta Biomaterialia, 7:2457–2466, 2011.
19
T. C. Gasser and G. A. Holzapfel. A rate-independent elastoplastic constitutive
model for (biological) fiber-reinforced composites at finite strains: Continuum
basis, algorithmic formulation and finite element implementation. Comput.
Mech., 29:340–360, 2002.
T. C. Gasser and G. A. Holzapfel. Modeling dissection propagation in soft

biological tissues. Eur. J. Mech. A/Solids, 25:617–633, 2006.
T. C. Gasser and G. A. Holzapfel. Modeling dissection failure during balloon

angioplasty. Ann. Biomed. Eng., 35:711–723, 2007.
T. C. Gasser, R. W. Ogden, and G. A. Holzapfel. Hyperelastic modelling of

arterial layers with distributed collagen fibre orientations. J. R. Soc. Interface,
3:15–35, 2006.
T. C. Gasser, G. Görgülü, M. Folkesson, and J. Swedenborg. Failure properties
of intra-luminal thrombus in Abdominal Aortic Aneurysm under static and
pulsating mechanical loads. J. Vasc. Surg., 48:179–188, 2008.
T. C. Gasser, S. Gallinetti, X. Xing, C. Forsell, J. Swedenborg, and J. Roy.

Spatial orientation of collagen fibers in the Abdominal Aortic Aneurysm wall
and its relation to wall mechanics. Acta Biomaterialia, 8:3091–3103, 2012.
T.C. Gasser, G. Martufi, M. Auer, M. Folkesson, and J. Swedenborg. Micro-
mechanical characterization of intra-luminal thrombus tissue from abdominal
aortic aneurysms. Ann. Biomed. Eng., 38:371–379, 2010.
T.C. Gasser, A. Nchimi, J. Swedenborg, J. Roy, N. Sakalihasan, D. Böckler, and

A. Hyhlik-Dürr. A novel strategy to translate the biomechanical rupture risk
of abdominal aortic aneurysms to their equivalent diameter risk: Method and
retrospective validation. Eur. J. Vasc. Endovasc. Surg., 47:288–295, 2014.
R.L. Gleason, E. Wilson, and J.D. Humphrey. Biaxial biomechanical adap-

tations of mouse carotid arteries cultured at altered axial extension. J.
Biomech., 40:766–776, 2007.
D. Gomez, A. Al Haj Zen, L.F. Borges, M. Philippe, P.S. Gutierrez, G. Jondeau,

and et al. Syndromic and non-syndromic aneurysms of the human ascending
aorta share activation of the smad2 pathway. J. Pathol., 218:131–142, 2009.
S. E. Greenwald, J. E. Moore, Jr., A. Rachev, T. P. C. Kane, and J.-J. Meister.
Experimental investigation of the distribution of residual strains in the artery
wall. J. Biomech. Eng., 119:438–444, 1997.
K. Grote, I. Flach, M. Luchtefeld, E. Akin, S.M. Holland, H. Drexler, and

B. Schieffer. Mechanical stretch enhances mRNA expression and proenzyme
release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived
reactive oxygen species. Circ. Res., 92:e80–e86, 2003.
20
N. Gundiah, A.R. Babu, and L.A. Pruitt. Effects of elastase and collagenase on
the nonlinearity and anisotropy of porcine aorta. Physiol. Meas., 34:1657–73,
2013.
X. Guo and G.S. Kassab. Variation of mechanical properties along the length
of the aorta. Am. J. Physiol. Heart Circ. Physiol., 285:H2614H2622, 2003.
R.J. Guzman, K. Abe, and C.K. Zarins. Flow-induced arterial enlargement is
inhibited by suppression of nitric oxide synthase activity in vivo. Surgery,
122:273–279, 1997.
S. S. Hans, O. Jareunpoon, M. Balasubramaniam, and G. B. Zelenock. Size and

location of thrombus in intact and ruptured Abdominal Aortic Aneurysms.
J. Vasc. Surg., 41:584–588, 2005.
R. Haverkamp, M. W. Williams, and J. E. Scott. Stretching single molecules
of connective tissue glycans to characterize their shape-maintaining elasticity.
Biomacromols, 6:1816–1818, 2005.
J. Hokanson and S. Yazdani. A constitutive model of the artery with damage.

Mech. Res. Commun., 24:151–159, 1997.
G. A. Holzapfel and T. C. Gasser. A viscoelastic model for fiber-reinforced

composites at finite strains: Continuum basis, computational aspects and
applications. Comput. Meth. Appl. Mech. Eng., 190:4379–4403, 2001.
G. A. Holzapfel, T. C. Gasser, and R. W. Ogden. A new constitutive framework
for arterial wall mechanics and a comparative study of material models. J.
Elasticity, 61:1–48, 2000.
C. O. Horgan and G. Saccomandi. A description of arterial wall mechan-

ics using limiting chain extensibility constitutive models. Biomech. Model.
Mechanobio., 1:251–266, 2003.
L. Horny, T. Adamek, and R. Zitny. Age-related changes in longitudinal pre-
stress in human abdominal aorta. Archive Appl. Mech., 83:875–888, 2013.
J. D. Humphrey and K. R. Rajagopal. A constrained mixture model for growth

and remodeling of soft tissues. Math. Model. Meth. Appl. Sci., 12:407–430,
2002.
I. Ionescu, J.E. Guilkey, M. Berzins, R.M. Kirby, and J. A. Weiss. Simulation
of soft tissue failure using the material point method. J. Biomech. Eng., 128:
917–94, 2006.
E. Knörzer, W. Folkhard, W. Geercken, C. Boschert, M. H. Koch, B. Hilbert,

H. Krahl, E. Mosler, H. Nemetschek-Gansler, and T. Nemetschek. New
aspects of the etiology of tendon rupture. An analysis of time-resolved
dynamic-mechanical measurements using synchrotron radiation. Arch. Or-
thop. Trauma. Surg., 105:113–120, 1986.
21
M. Kroon and G.A. Holzapfel. A theoretical model for fibroblast-controlled
growth of saccular cerebral aneurysms. J. Theor. Biol., 257:73–83, 2009.
G. J. Langewouters, K. H. Wesseling, and W. J. A. Goedhard. The static
elastic properties of 45 human thoracic and 20 abdominal aortas in vitro and
the parameters of a new model. J. Biomech., 17:425–435, 1984.
Y. Lanir. Constitutive equations for fibrous connective tissues. J. Biomech., 16:
1–12, 1983.
S. Laurent, J. Cockcroft, L. Van Bortel, P. Boutouyrie, C. Giannattasio,
D. Hayoz, B. Pannier, C. Vlachopoulos, I. Wilkinson, and H. Struijker-
Boudier. Expert consensus document on arterial stiffness: methodological
issues and clinical applications. Eur. Heart J., 27:2588 2605, 2006.
D. Y. Leung, S. Glagov, and M. B. Mathews. Cyclic stretching stimulates syn-
thesis of matrix components by arterial smooth muscle cells in vitro. Science,
191:475–477, 1976.
J. Liao and I. Vesely. Skewness angle of interfibrillar proteoglycans increases
with applied load on mitral valve chordae tendineae. J. Biomech., 40:390–398,
2007.
J. Lu, X. Zhou, and M. L. Raghavan. Inverse elastostatic stress analysis in
pre-deformed biological structures: Demonstration using Abdominal Aortic
Aneurysms. J. Biomech., 40:693–696, 2007.
A. Maier, M. Essler, M. W. Gee, H. H. Eckstein, W. A. Wall, and C. Reeps.
Correlation of biomechanics to tissue reaction in aortic aneurysms assessed
by finite elements and [18f]-fluorodeoxyglucose-pet/ct. Int. J. Numer. Meth.
Biomed. Eng., 28:456–471, 2012.
G. Marini, A. Maier, C. Reeps, H.-H. Eckstein, W. A. Wall, and M. W. Gee. A
continuum description of the damage process in the arterial wall of abdominal
aortic aneurysms. Int. J. Numer. Meth. Bioeng., 2011.
V. Marque, P. Kieffer, B. Gayraud, I. Lartaud-Idjouadiene, F. Ramirez, and
J. Atkinson. Aortic wall mechanics and composition in a transgenic mouse
model of Marfan syndrome. Arterioscl. Thromb. and Vasc. Biol., 21:1184–
1189, 2001.
J.N. Marsh, S. Takiuchi, S.J. Lin, G.M. Lanza, and S.A. Wickline. Ultrasonic
delineation of aortic microstructure: the relative contribution of elastin and
collagen to aortic elasticity. J. Acoust. Soc. Am., 115:20322040, 2004.
G. Martufi and T. C. Gasser. A constitutive model for vascular tissue that
integrates fibril, fiber and continuum levels. J. Biomech., 44:2544–2550, 2011.
G. Martufi and T. C. Gasser. Turnover of fibrillar collagen in soft biological
tissue with application to the expansion of abdominal aortic aneurysms. J.
R. Soc. Interface, 9:3366–3377, 2012.
22
G. Martufi, M. Lindquist Liljeqvist, N. Sakalihasan, G. Panuccio, R. Hultgren,
J. Roy, and T.C. Gasser. Local diameter, wall stress and thrombus thickness
influence the local growth of abdominal aortic aneurysms. J. Endovas. Ther.,
23:957–966, 2016.
T. Matsumoto and K. Hayashi. Stress and strain distribution in hypertensive
and normotensive rat aorta considering residual strain. J. Biomech., 118:
62–73, 1996.
M. Bäck, T.C. Gasser, J.-B. Michel, and G. Caligiuri. Review. biomechanical
factors in the biology of aortic wall and aortic valve diseases. Cardiovasc.
Res., 99:232–241, 2013.
S. de Putter, B.J.B.M. Wolters, M.C.M. Rutten, M. Breeuwer, F.A. Gerritsen,
and F.N. van de Vosse. Patient-specific initial wall stress in Abdominal Aortic
Aneurysms with a backward incremental method. J. Biomech., 40:1081–1090,
2007.
E. S. DiMartino, A. Bohra, J. P. Vande Geest, N. Gupta, M. S. Makaroun, and
D. A. Vorp. Biomechanical properties of ruptured versus electively repaired
Abdominal Aortic Aneurysm wall tissue. J. Vasc. Surg., 43:570–576, 2006.
T. Länne, B. Sonesson, D. Bergqvist, H. Bengtsson, and D. Gustafsson. Diame-
ter and compliance in the male human abdominal aorta: Influence of age and
aortic aneurysm. Eur. J. Vasc. Surg., 6:178–184, 1992.
J. P. Vande Geest, , E. D. Dillavou, E. S. DiMartino, M. Oberdier, A. Bohra,
M. S. Makaroun, and D. A. Vorp. Gender-related differences in the tensile
strength of Abdominal Aortic Aneurysm. Ann. N.Y. Acad. Sci., 1085:400–
402, 2006a.
J. P. Vande Geest, M. S. Sacks, and D. A. Vorp. The effects of aneurysm on
the biaxial mechanical behavior of human abdominal aorta. J. Biomech., 39:
1324–1334, 2006b.
J. P. Vande Geest, M. S. Sacks, and D. A. Vorp. A planar biaxial constitutive
relation for the luminal layer of intra-luminal thrombus in Abdominal Aortic
Aneurysms. J. Biomech., 39:2347–2354, 2006c.
J. P. Vande Geest, D. H. J. Wang, S. R. Wisniewski, M. S. Makaroun, and D. A.
Vorp. Towards a noninvasive method for determination of patient-specific wall
strength distribution in Abdominal Aortic Aneurysms. Ann. Biomed. Eng.,
34:1098–1106, 2006d.
D. A. McDonald. Blood flow in arteries. Edward Arnold, London, 6th edition,
2011.
D. M. Milewicz, C. S. Kwartler, C. L. Papke, E. S. Regalado, J. Cao, and
A. J. Reid. Genetic variants promoting smooth muscle cell proliferation can
result in diffuse and diverse vascular diseases: Evidence for a hyperplastic
vasculomyopathy. Genetics in Medicine, 12:196–203, 2010.
23
H. Miyazaki and K. Hayashi. Tensile tests of collagen fibers obtained from the
rabbit patellar tendon. Biomedical Microdevices, 2:151–157, 1999.
D. Mohan and J. W. Melvin. Failure properties of passive human aortic tissue

I - uniaxial tension tests. J. Biomech., 15:887–902, 1982.
J.A. Tavares Monteiro, E.S. da Silva, M.L. Raghavan, P. Puech-Le ao,

M. de Lourdes Higuchi, and J.P. Otoch. Histologic, histochemical, and biome-
chanical properties of fragments isolated from the anterior wall of abdominal
aortic aneurysms. J. Vasc. Surg., 59:1393–1401, 2013.
A. Nchimi, J.-P. Cheramy-Bien, T.C. Gasser, G. Namur, P. Gomez, A. Albert,

L. Seidel, J.O. Defraigne, N. Labropoulos, and N. Sakalihasan. Multifactorial
relationship between 18f-fluoro-deoxy-glucose positron emission tomography
signaling and biomechanical properties in unruptured aortic aneurysms. Circ.
Cardiovasc. Imaging, 7:82–91, 2014.
W. W. Nichols, M. F. O’Rourke, and C. Vlachopoulos. McDonald’s Blood Flow
in Arteries, Sixth Edition. Theoretical, experimental and clinical principles.
Arnold, London, 6th edition, 2011.
R. Nissen, G.J. Cardinale, and S. Udenfriend. Increased turnover of arterial

collagen in hypertensive rats. Proc. Natl. Acad. Sci. USA, 75:451–453, 1978.
C. Noble, N. Smulders, N. H. Green, R. Lewis, M. J. Carr, S. E. Franklin,

S. MacNeil, and Z. A. Taylor. Creating a model of diseased artery damage
and failure from healthy porcine aorta. J. Mech. Behav. Biomed. Mater.,
(submitted), 2016.
M.K. O’Connell, S. Murthy, S. Phan, C. Xu, J. Buchanan, R. Spilker, R.L.

Dalman, C.K. Zarins, W. Denk, and C.A. Taylor. The three-dimensional
micro- and nanostructure of the aortic medial lamellar unit measured using
3d confocal and electron microscopy imaging. Matrix Biol., 27:171–181, 2008.
R. W. Ogden. Large deformation isotropic elasticity – on the correlation of

theory and experiment for incompressible rubberlike solids. Proc. R. Soc.
Lond. A, A326:565–584, 1972.
S. Oka and T. Azuma. Physical theory of tension in thick walled blood vessels
in equilibrium. Biorheology, 7:109–118, 1970.
H. S. Oktay, T. Kang, J. D. Humphrey, and G. G. Bishop. Changes in the

mechanical behavior of arteries following balloon angioplasty. In ASME 1991
Biomechanics Symposium, AMD-Vol. 120. American Society of Mechanical
Engineers, 1991.
S.A. O’Leary, D. Healy, E.G. Kavanagh, M.T. Walsh, T.M. McGloughlin, and
B.J. Doyle. The biaxial biomechanical behavior of abdominal aortic aneurysm
tissue. Ann. Biomed. Eng., 42:2440–2450, 2014.
24
S.A. O’Leary, J.J. Mulvihill, H.E. Barrett, E.G. Kavanagh, M.T. Walsh, T.M.
McGloughlin, and B.J. Doyle. Determining the influence of calcification on
the failure properties of abdominal aortic aneurysm (AAA) tissue. J. Mech.
Behav. Biomed. Mater., 42:154–167, 2015.
J. Papakrivopoulou, G.E. Lindahl, J.E. Bishop, and G.J. Laurent. Differential

roles of extracellular signal-regulated kinase 1/2 and p38MAPK in mechanical
load-induced procollagen alpha1(I) gene expression in cardiac fibroblasts. 61:
736–744, 2004.
D. J. Patel, J. S. Janicki, and T. E. Carew. Static anisotropic elastic properties

of the aorta in living dogs. Circ. Res., 25:765–779, 1969.
J.E. Pichamuthu, J.A. Phillippi, D.A. Cleary, D.W. Chew, J. Hempel, D.A.
Vorp, and T.G. Gleason. Differential tensile strength and collagen composi-
tion in ascending aortic aneurysms by aortic valve phenotype. Ann. Thorac
Surg., 96:21472154, 2013.
S. Polzer, T.C. Gasser, B. Markert, J. Bursa, and P. Skacel. Impact of poroe-

lasticity of the intraluminal thrombus on the wall stress of abdominal aortic
aneurysms. Biomed. Eng. Online, 11:doi:10.1186/1475–925X–11–62, 2012.
S. Polzer, J. Bursa, T.C. Gasser, and R. Staffa andd R. Vlachovsky. Numer-
ical implementation to predict residual strains from the homogeneous stress
hypothesis with application to abdominal aortic aneurysms. Ann. Biomed.
Eng., 41:1516–1527, 2013.
S. Polzer, T.C. Gasser, K. Novak, V. Man, M. Tichy, P. Skacel, and J. Bursa.
Structure-based constitutive model can accurately predict planar biaxial
properties of aortic wall tissue. Acta Biomaterialia, 14:133–145, 2015.
K. P. Quinn and B. A. Winkelstein. Altered collagen fiber kinematics define

the onset of localized ligament damage during loading. J. Appl. Physiol., 105:
1881–1888, 2008.
R. R. Ross and P. Bornstein. The elastic fiber: I. the separation and partial
characterization of its macromolecular components. J. Cell Biol., 40:366–381,
1969.
A. Rachev and S. E. Greenwald. Residual strains in conduit arteries. J.
Biomech., 36:661–670, 2003.
A. Rachev and K. Hayashi. Theoretical study of the effects of vascular smooth
muscle contraction on strain and stress distributions in arteries. Ann. Biomed.
Eng., 27:459–468, 1999.
A. Rachev, N. Stergiopulos, and J.-J. Meister. Theoretical study of dynamics of

arterial wall remodeling in response to changes in blood pressure. J. Biomech.,
29:635–642, 1996.
25
A. Rachev, S. E. Greenwald, and T. Shazly. Are geometrical and struc-
tural variations along the length of the aorta governed by a principle of
Optimal Mechanical Operation? J. Biomech. Eng., 135:10.1115/SBC2013–
14427, 2013.
M. L. Raghavan and D. A. Vorp. Toward a biomechanical tool to evaluate

rupture potential of Abdominal Aortic Aneurysm: identification of a finite
strain constitutive model and evaluation of its applicability. J. Biomech., 33:
475–482, 2000.
M. L. Raghavan, M. W. Webster, and D. A. Vorp. Ex vivo biomechanical be-

havior of Abdominal Aortic Aneurysm: assesment using a new mathematical
model. Ann. Biomed. Eng., 24:573–582, 1996.
M. L. Raghavan, J. Kratzberg, E. Castro de Tolosa, M. Hanaoka, P. Walker,
and E. da Silva. Regional distribution of wall thickness and failure properties
of human Abdominal Aortic Aneurysm. J. Biomech., 39:3010 – 3016, 2006.
M.L. Raghavan, M.M. Hanaoka, J.A. Kratzberg, M. de Lourdes Higuchi, and

E.S. da Silva. Biomechanical failure properties and microstructural content
of ruptured and unruptured abdominal aortic aneurysms. J. Biomech., 44:
2501–2507, 2011.
A. Redaelli, S. Vesentini, M. Soncini, P. Vena, S. Mantero, and F. M. Mon-

tevecchi. Possible role of decorin glycosaminoglycans in fibril to fibril force
transfer in relative mature tendons–a computational study from molecular to
microstructural level. J. Biomech., 36:1555–1569, 2003.
C. Reeps, A. Maier, J. Pelisek, F. Hartl, V. Grabher-Maier, W.A. Wall,

M. Essler, H.-H. Eckstein, and M.W. Gee. Measuring and modeling patient-
specific distributions of material properties in abdominal aortic wall. Biomech.
Model. Mechanobio., 12:717–733, 2013.
S. Rigozzi, R. Mueller, and J.G. Snedeker. Local strain measurement reveals a

varied regional dependence of tensile tendon mechanics on glycosaminoglycan
content. J. Biomech., 42:1547–1552, 2009.
S. Rigozzi, R. Mueller, and J.G. Snedeker. Collagen fibril morphology and

mechanical properties of the achilles tendon in two inbred mouse strains. J.
Anat., 216:724–731, 2010.
F. Riveros, S. Chandra, E.A. Finol, T.C. Gasser, and J.F. Rodriguez. A pull-
back algorithm to determine the unloaded vascular geometry in anisotropic
hyperelastic aaa passive mechanics. Ann. Biomed. Eng., 41:694–708, 2013.
M. R. Roach and A. C. Burton. The reason for the shape of the distensibility
curve of arteries. Canad. J. Biochem. Physiol., 35:681–690, 1957.
26
P. S. Robinson, T. F. Huang, E. Kazam, R.V. Iozzo, D. E. Birk, and L. J.
Soslowsky. Influence of decorin and biglycan on mechanical properties of
multiple tendons in knockout mice. J. Biomech. Eng., 127:181–185, 2005.
J. F. Rodrı́guez, C. Ruiz, M. Doblaré, and G.A. Holzapfel. Mechanical stresses in

abdominal aortic aneurysms: influence of diameter, asymmetry, and material
anisotropy. 130:021023, 2008.
J. F. Rodrı́guez, G. Martufi, M. Doblaré, and E. Finol. The effect of material

model formulation in the stress analysis of abdominal aortic aneurysms. Ann.
Biomed. Eng., 37:: 22182221, 2009.
C. S. Roy. The elastic properties of the arterial wall. J. Physiol., 3:125–159,
1880–82.
N. V. Salunke and L. D. T. Topoleski. Biomechanics of atherosclerotic plaque.
Crit. Rev. Biomed. Eng., 25:243–285, 1997.
Z. J. Samila and S. A. Carter. The effect of age on the unfolding of elastin
lamellae and collagen fibers with stretch in human carotid arteries. Canad.
J. Physiol. Pharm., 59:1050–1057, 1981.
R.G. Sargent. Verification and validation of simulation models. In S. Jain, R.R.

Creasey, J. Himmelspach, K.P. White, and M. Fu, editors, Proceedings of the
2011 Winter Simulation Conference, pages 183–198. Institute of Electrical
and Electronic Engineers Inc, 2011.
N. Sasaki and S. Odajima. Elongation mechanism of collagen fibrils and force-

strain relations of tendon at each level of the structural hierarchy. J. Biomech.,
29:1131–1136, 1996.
A.J. Schriefl, G. Zeindlinger, D.M. Pierce, P. Regitnig, and G.A. Holzapfel.
Determination of the layer-specific distributed collagen fiber orientations in
human thoracic and abdominal aortas and common iliac arteries. J. R. Soc.
Interface, 7:1275–1286, 2012.
J. E. Scott. Elasticity in extracellular matrix ’shape modules’ of tendon, carti-

lage, etc. A sliding proteoglycan-filament model. J. Physiol., 553.2:335–343,
2003.
J. E. Scott. Cartilage is held together by elastic glycan strings. Physiological
and pathological implications. Biorheology, 45:209–217, 2008.
B. Sharifimajd and J. Stålhand. A continuum model for excitationcontraction
of smooth muscle under finite deformations. J. Theor. Biol., 355:1–9, 2014.
B. R. Simon and M. A. Gaballa. Finite strain, poroelastic finite element models
for large arterial cross sections. Comput. Meth. Biomech. Biomed. Eng., 9:
325–333, 1988.
27
D. P. Sokolis. Passive mechanical properties and structure of the aorta: seg-
mental analysis. Acta Physiol., 190:277–289, 2007.
D. P. Sokolis, E.M. Kefaloyannis, M. Kouloukoussa, E. Marinos, H. Boudoulas,
and P.E. Karayannacos. A structural basis for the aortic stressstrain relation
in uniaxial tension. J. Biomech., 39:16511662, 2006.
B. Sonesson, F. Hansen, H. Stale, and T. Länne. Compliance and diameter in
the huma abdomial aorta - The influence of age and sex. Eur. J. Vasc. Surg.,
7:690–697, 1993.
N. T. Soskel and L. B.Sandberg. Pulmonary emphysema. From animal models
to human diseases, in Connective tissue disease. Molecular pathology of the
extracellular matrix. Dekker, New York, 1987.
J. Stålhand and A. Klarbring. Aorta in vivo parameter identification using an
axial force constraint. Biomech. Model. Mechanobio., 2005. In Press.
J. Stålhand, A. Klarbring, and M. Karlsson. Towards in vivo material iden-
tification and stress estimation. Biomech. Model. Mechanobio., 2:169–186,
2004.
L. A. Taber and J. D. Humphrey. Stress-modulated growth, residual stress, and
vascular heterogeneity. J. Biomech. Eng., 123:528–535, 2001.
K. Takamizawa and K. Hayashi. Strain energy density function and uniform
strain hypothesis for arterial mechanics. J. Biomech., 20:7–17, 1987.
A. M. Tamburro, A. DeStradis, and L. D’Alessio. Fractal aspects of elastin
supramolecular structure. J. Biomol. Struct. Dyn., 12:1161–1172, 1995.
E. Tanaka and H. Yamada. An inelastic constitutive model of blood vessels.
Acta Mech., 82:21–30, 1990.
T. T. Tanaka and Y. C. Fung. Elastic and inelastic properties of the canine
aorta and their variation along the aortic tree. J. Biomech., 7:357–370, 1974.
M.J. Thubrikar, M. Labrosse, F. Robicsek, J. Al-Soudi, and B. Fowler. Mechan-
ical properties of abdominal aortic aneurysm wall. J. Med. Eng. Technol., 25:
133–142, 2001.
J. R. Thunes, S. Pal, R. N. Fortunato, J. A. Phillippi, G. Gleason, D. A. Vorp,
and S. Maiti. A structural finite element model for lamellar unit of aor-
tic media indicates heterogeneous stress field after collagen recruitment. J.
Biomech., doi: 10.1016:ahead of print, 2016.
R. N. Vaishnav and J. Vossoughi. Residual stress and strain in aortic segments.
J. Biomech., 20:235–239, 1987.
R. N. Vaishnav, J. T. Young, J. S. Janicki, and D. J. Patel. Nonlinear anisotropic
elastic properties of the canine aorta. Biophys. J., 12:1008–1027, 1972.
28
S. Vesentini, A. Redaelli, and F. M. Montevecchi. Estimation of the binding
force of the collagen molecule-decorin core protein complex in collagen fibril.
J. Biomech., 2005.
J.F. Vollmar, E. Paes, P. Pauschinger, E. Henze, and A. Friesch. Aortic
aneurysms as late sequelae of above-knee amputation. Lancet, 2:834–835,
1989.
K.Y. Volokh and D. A. Vorp. A model of growth and rupture of abdominal
aortic aneurysm. J. Biomech., 41:1015–1021, 2008.
D. A. Vorp, M. L. Raghavan, S. C. Muluk, M. S. Makaroun, D. L. Steed,
R. Shapiro, and M. W. Webster. Wall strength and stiffness of aneurysmal
and nonaneurysmal abdominal aorta. Ann. N.Y. Acad. Sci., 800:274–276,
1996.
D. A. Vorp, P. C. Lee, D. H. Wang, M. S. Makaroun, E. M. Nemoto, S. Ogawa,
and M. W. Webster. Association of intraluminal thrombus in Abdominal
Aortic Aneurysm with local hypoxia and wall weakening. J. Vasc. Surg., 34:
291–299, 2001.
D. A. Vorp, B. J. Schiro, M. P. Ehrlich, T. S. Juvonen, M. A. Ergin, and
B. P. Griffith. Effect of aneurysm on the tensile strength and biomechanical
behavior of the ascending thoracic aorta. Ann. Thorac Surg., 800:1210–1214,
2003.
J. Vossoughi. Longitudinal residual strains in arteries. In Proceedings of the 11th
Southern Biomedical Engineering Conference, Memphis, TN, 1992. October
2–4, 1992, pp. 17–19.
B. Vrhovski and A.S. Weiss. Biochemistry of tropoelastin. Eur. J. Biochem.,
258:1–18, 1998.
P. N. Watton and N. A. Hill. Evolving mechanical properties of a model of
Abdominal Aortic Aneurysm. Biomech. Model. Mechanobio., 8:25–42, 2009.
H. W. Weizsäcker, H. Lambert, and K. Pascale. Analysis of the passive me-
chanical properties of rat carotid arteries. J. Biomech., 16:703–715, 1983.
Z. Werb, M. J. Banda, J. H. McKerrow, and R. A. Sandhaus. Elastases and
elastin degradation. J. Invest. Dermatol., 79:154–159, 1982.
N. Westerhof, J.-W. Lankhaar, and B. E. Westerhof. The arterial windkessel.
Med. & Biol. Eng. & Comput., 47:131–141, 2009.
J. S. Wilson, S. Baek, and J. D. Humphrey. Importance of initial aortic proper-
ties on the evolving regional anisotropy, stiffness and wall thickness of human
abdominal aortic aneurysms. J. R. Soc. Interface, 2012. (ahead of print).
H. Wolinsky. Effects of hypertension and its reversal on the thoracic aorta of
male and female rats. Circ. Res., 28:622–637, 1971.
29
H. Wolinsky and S. Glagov. Structural basis for the static mechanical properties
of the aortic media. Circ. Res., 14:400–413, 1964.
F. L. Wuyts, V. J. Vanhuyse, G. J. Langewouters, W. F. Decraemer, E. R.

Raman, and S. Buyle. Elastic properties of human aortas in relation to age
and atherosclerosis: A structural model. Phys. Med. Biol., 40:1577–1597,
1995.
J. Xiong, S.M. Wang, W. Zhou, and J.G. Wu. Measurement and analysis of
ultimate mechanical properties, stress-strain curve fit, and elastic modulus
formula of human abdominal aortic aneurysm and nonaneurysmal abdominal
aorta. J. Vasc. Surg., 48:189–195, 2008.
O. H. Yeoh. Some forms of strain energy functions for rubber. Rubber Chem.
Technol., 66:754–771, 1993.
S. Zeinali-Davarani and S. Baek. Medical image-based simulation of abdominal

aortic aneurysm growth. Mech. Res. Commun., 42:107–117, 2012.
S. Zeinali-Davarani, M.-J. Chow, R. Turcotte, and Y. Zhang. Characteriza-

tion of biaxial mechanical behavior of porcine aorta under gradual elastin
degradation. Ann. Biomed. Eng., 41:1528–1538, 2013.
M. A. Zulliger and N. Stergiopulos. Structural strain energy function applied
to the ageing of the human aorta. J. Biomech., 40:30613069, 2007.
M. A. Zulliger, P. Fridez, K. Hayashi, and N. Stergiopulos. A strain energy func-
tion for arteries accounting for wall composition and structure. J. Biomech.,
37:989–1000, 2004a.
M. A. Zulliger, A. Rachev, and N. Stergiopulos. A constitutive formulation of

arterial mechanics including vascular smooth muscle tone. Am. J. Physiol.
Heart Circ. Physiol., 287:H1335–H1343, 2004b.
30
Reference Sample specification Thickness Strength
[mm] [MPa]
[O’Leary et al., 2015] N=31; fibrous 1.2 1.2
N=38; partly calcified 1.5 0.87
[O’Leary et al., 2014] N=28 1.18 -
[Vande Geest et al., 2006d] N=83 - 0.81
[Vande Geest et al., 2006b] N=26 1.32 -
[Monteiro et al., 2013] N=25; AAA diam. < 55mm 1.53 0.77
N=65; AAA diam. > 55mm 1.58 1.03
[Vande Geest et al., 2006a] N=76 - Female: 0.68
Male: 0.88
[Reeps et al., 2013] N=163 1.57 1.42
[Raghavan et al., 2006] N=374/48 1.48 1.26
[Xiong et al., 2008] N=14 1.5 to 1.9 Long.: 0.93
Circ.: 1.15
[Forsell et al., 2012] N=16 2.06 0.57
[Thubrikar et al., 2001] Anterior: N=29 2.73 Long.: 0.38
Circ.: 0.52
Lateral: N=9 2.52 Long.: 0.51
Circ.: 0.73
Posterior: N=9 2.09 Long.: 0.47
Circ.: 0.45
[DiMartino et al., 2006] Intact AAA: N=26 2.5 0.82
Ruptured AAA: N=13 3.6 0.54
[Raghavan et al., 2011] Intact: N=278/56 1.5 0.98
Ruptured: N= 141/21 1.7 0.95
[Raghavan et al., 1996] Long.: N=45 - 0.86
Circ.: N=19 - 1.02
[Vorp et al., 2001] ILT layer thick. > 4mm: N=7 - 1.38
ILT layer thick. < 4mm: N=7 - 2.16
Table 1: Abdominal Aortic Aneurysm (AAA) wall thickness and wall strength
measured from in-vitro tensile testing. The number of test samples is denoted by
N (used for thickness/ strength measurements). Circ. - circumferential; Long.
- longitudinal; ILT - intra-luminal thrombus.
31
(a) Isotropic
Model frame Strain energy function Parameter identification
N
N = 2: [Raghavan and Vorp, 2000, Raghavan
∑ et al., 1996, Reeps et al., 2013, Vande Geest et al.,
[Yeoh, 1993] ψ= ci (I1 − 3)i
2006c]
i=1
N = 5: [Polzer et al., 2013]
[Demiray, 1981] ψ = c0 exp[c1 (I1 − 3) − 1] [Polzer et al., 2013, Riveros et al., 2013]
3
∑
[Ogden, 1972] ψ = c0 (λ4i − 1) [Gasser et al., 2008]
i
(b) Anisotropic
Model frame Strain energy function Parameter identification
[Chuong and Fung, 1983] ψ = c0 {exp[Q] − 1} ,
2 2 2
Q = c1 Eϑϑ + c2 Ezz + c3 Err + c4 Eϑϑ Ezz + c5 Ezz Err
2 2 2 [Zulliger et al., 2004a]
+c{6 Err Eϑϑ + c7 Eϑz + c8 Erz + c9 Erϑ }
2 2
[Choi and Vito, 1990] ψ = c0 exp[c1 Eϑϑ ] + exp[c2 Ezz ] + exp[c3 Eϑϑ Ezz ] − 3 [Vande Geest et al., 2006b]
[Riveros et al., 2013] ψ = c0 {exp[c1 (I1 − 3)] − 1} + c2 {exp[c3 (I4 − 1)] − 1} [Riveros et al., 2013]
2
∑ [Basciano and Kleinstreuer, 2009, Vande Geest
[Basciano and Kleinstreuer, 2009] ψ = c0 (I1 − 3) + c1 (I4 i − 1)6
et al., 2006b]
i=1
N N=2: [Zeinali-Davarani et al., 2013, Zulliger et al.,
32
∑
[Holzapfel and Gasser, 2001] ψ = c0 (I1 − 3) + c1 i {exp[c2 i (I4 i − 1)2 ] − 1} 2004a, Stålhand et al., 2004]
i=1 N=4: [Baek et al., 2009, Ferruzzi et al., 2010]
2
∑
[Rodrı́guez et al., 2008] ψ = c0 (I1 − 3) + c1 {exp[Q] − 1} ,
i=1
[Rodrı́guez et al., 2008, 2009, Vande Geest et al.,
Q = c2 [c3 (I4 i − c4 )2 + (1 − c3 )(I1 − 3)2 ]
2006b]
3 2
∑ ∑
[Celi and Berti, 2012] ψ= c0 i (I1 − 3)i + c1 i (I4 i − 1)i [Celi and Berti, 2012]
i=1 i=1
N
∑
[Gasser et al., 2006] ψ = c0 (I1 − 3) + c1 [exp(c2 Ei2 ) − 1] ; Ei = Hi : C − 1 [Noble et al., 2016]
i=1
General structural tensor: Hi = κI + (1 − 3κ)(a0 i ⊗ a0 i )
Table 2: Hyperelastic strain energy functions to model aortic tissue stress according to eq.(1). I1 = trC denotes the first
invariant of the right Cauchy-Green strain C. I4 i = C : (a0 i ⊗ a0 i ) denotes the fourth invariant of C and the structural tensor
a0 i ⊗ a0 i , where the unit direction vector a0 i defines the fiber orientation of the i−th family of parallel-aligned (collagen)
fibers. For collagen fibers that are dispersed in orientation, a0 i denotes their mean orientation and κ is a measure of their
dispersion. Eij ; i, j = r, ϑ, z denotes the components of the Green-Lagrange strain E = (C − I)/2 with respect to the local
cylindrical coordinate system of radial r, circumferential ϑ and axial z vessel directions. Model parameters to be identified
from experimental data are denoted by ci , a0 i and κ.
Model frame ∫ Parameter identification
ε
[Decraemer et al., 1980] σ(ε) = c0 (ε − x)ρ(x)dx
−∞
c1
with Cauchy-Lorentz probability distribution: ρ(x) = 2
[Wuyts et al., 1995]
{2π[c /4
{ c (x−c 1/c )c1 −1+ (x − c2 )2 ]}
1 3 2
c2 [1+(x−c3 /c2 )c2 ]2
for x ≤ c3
with log-logistic probability distribution: ρ(x) = [Zulliger et al., 2004a] (carotid)
0 for x > c3

 0 , λ ≤ c1

∫ λ  1 [Martufi and Gasser, 2011,
 2c0 λ (λ−c1 )32
3(c2 −c1 )
, c 1 < λ ≤ c2 +c
2
[Martufi and Gasser, 2011] σ(λ) = c0 λ CDF∆ (x)dx = [ ] Gasser et al., 2012, Polzer
(λ−c2 )3 c2 +c1 c2 +c1
−∞ 
 c0 λ λ − 2 3(c2 −c1 )2 − 2 , 2
< λ ≤ c2 et al., 2015]

 ( )
1
c0 λ λ − c2 +c
2
, c2 < λ ≤ ∞.
CDF∆ (x): Cumulative Density Function of the triangular probability distribution
33
{
0 , λ≤1
[Gasser et al., 2012] σ(λ) = [Gasser et al., 2012]
2c λ(1 + c1 sin θ)(λ2 − 1) exp[c2 (λ2 − 1)] , 1 < λ ≤ ∞
{ 0
0 , λ ≤ c0
[Gasser, 2011] σ(λ) = [Gasser, 2011]
c1 λ2 (λ/c0 − 1) , c0 < λ ≤ ∞
{ [Miyazaki and Hayashi,
0 , λ ≤ c0
[Thunes et al., 2016] σ(λ) = 1999, Zulliger and Stergiop-
c1 (λ − c0 ) , c0 < λ ≤ ∞
ulos, 2007]
Table 3: Constitutive assumptions to model the (gradual) engagement of collagen fibrils. Fiber stress σ is expressed with
respect to the applied fiber stretch λ or the fiber strain ε = λ − 1. Model parameters to be identified from experimental
data are denoted by ci , and θ denotes the azimuthal fiber orientation angle, i.e. its orientation with respect to the vessel’s
circumferential direction.
View publication stats
Collagen orientation density model Parameter identification
Transverse isotropy [Gasser et al., 2006] ρ(ϕ) = c exp{c0 [cos(2ϕ) + 1]} [Schriefl et al., 2012]
Planar von Mises ρ(ϕ) = c exp[c0 cos(2ϕ)] [Polzer et al., 2015]
Bingham [Bingham, 1974] ρ(ϕ, θ) = c exp[c0 (cos ϕ cos θ)2 + c1 (cos ϕ sin θ)2 ] [Gasser et al., 2012]
34
Direct experimental histogram data [Pichamuthu et al., 2013, Thunes et al., 2016]
Table 4: Modeling the orientation of collagen fibers in the aortic wall. The orientation of a fiber in space is describe by
azimuthal θ and elevation ϕ angles. Model∫parameters to be identified from experimental data are denoted by ci and c denotes
a normalization parameter to ensure that ω ρdω = 1, i.e. when integrating over the all directions.

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Chapter · December 2017

Thomas Christian Gasser

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2 Histology and morphology of the aorta 3

3 Mechanical properties and experimental observations 9

2 Histology and morphology of the aorta

2.1 Extra cellular matrix (ECM)

2.1.1 Collagen structure

The media is formed by Medial Lamel-

Figure 1: Histological idealization of the normal aorta. It is composed of three

Vessle Layer Thickness (mm)

Outer Vessle Diameter (mm)

Figure 2: Variation of geometrical properties and histological composition of the

2.1.2 Elastin structure

3 Mechanical properties and experimental ob-

4.1 Modeling frameworks

where m = FM denotes the push forward of the referential ﬁber direction M.

4.2 Purely phenomenological descriptions

4.3 Histo-mechanical descriptions

4.4 Damage and failure descriptions

4.5 Growth and Remodeling descriptions

R. Adolph, D. A. Vorp, D. L. Steed, M. W. Webster, M. V. Kameneva, and

H. Astrand, J. Stålhand, J. Karlsson, M. Karlsson, and B. Sonesson Band T.

S. Baek, R. Gleason, K. R. Rajagopal, and J. D. Humphrey. Theory of small on

C.A. Basciano and C. Kleinstreuer. Invariant-based anisotropic constitutive

C. L. Berry and S. E. Greenwald. Eﬀect of hypertension on the static mechanical

C. Bingham. An antipodally symmetric distribution on the sphere. Ann. Statist.,

J. E. Bishop and G. Lindahl. Regulation of cardiovascular collagen synthesis by

B. Calvo, E. Peña, P. Martins, T. Mascarenhas, M Doblaré, R. M. Natal Jorge,

X.-L. Chen, S. E. Varner, A. S. Rao, J. Y. Grey, S. Thomas, C. K. Cook, M. A.

H. S. Choi and R. P. Vito. Two-dimensional stress-strain relationship for canine

C. J. Chuong and Y. C. Fung. Three-dimensional stress distribution in arteries.

PF Davies. Flow-mediated endothelial mechanotransduction. Physiol. Rev., 75:

W. F. Decraemer, M. A. Maes, and V. J. Vanhuyse. An elastic stress-strain

P. B. Dobrin and T. R. Canﬁeld. Elastase, collagenase, and the biaxial elastic

J. L. Emery, J. H. Omens, and A. D. McCulloch. Strain softening in rat left

J. L. Emery, J. H. Omens, and A. D. McCulloch. Biaxial mechanics of the

G. Fessel and J. G. Snedeker. Equivalent stiﬀness after glycosaminoglycan de-

H. M. Finlay, L. McCullough, and P. B. Canham. Three-dimensional collagen

C. Forsell, T. C. Gasser, J. Swedenborg, and J. Roy. The quasi-static

C. Forsell, H. M. Bjrck, P. Eriksson, A. Franco-Cereceda, and T. C. Gasser.

P. Fratzl, editor. Collagen - Structure and Mechanics. Springer-Verlag, New

P. Fridez, A. Makino, H. Miyazaki, J. J. Meister, K. Hayashi, and N. Ster-

T. Fujiwara and Y. Uehara. The cytoarchitecture of the medial layer in rat

Y. C. Fung. Biomechanics. Motion, Flow, Stress, and Growth. Springer-Verlag,

Y. C. Fung, K. Fronek, and P. Patitucci. Pseudoelasticity of arteries and the

T. C. Gasser. An irreversible constitutive model for ﬁbrous soft biological tis-

T. C. Gasser and G. A. Holzapfel. Modeling dissection propagation in soft

T. C. Gasser and G. A. Holzapfel. Modeling dissection failure during balloon

T. C. Gasser, R. W. Ogden, and G. A. Holzapfel. Hyperelastic modelling of

T. C. Gasser, S. Gallinetti, X. Xing, C. Forsell, J. Swedenborg, and J. Roy.

T.C. Gasser, A. Nchimi, J. Swedenborg, J. Roy, N. Sakalihasan, D. Böckler, and

R.L. Gleason, E. Wilson, and J.D. Humphrey. Biaxial biomechanical adap-

D. Gomez, A. Al Haj Zen, L.F. Borges, M. Philippe, P.S. Gutierrez, G. Jondeau,

K. Grote, I. Flach, M. Luchtefeld, E. Akin, S.M. Holland, H. Drexler, and

S. S. Hans, O. Jareunpoon, M. Balasubramaniam, and G. B. Zelenock. Size and

J. Hokanson and S. Yazdani. A constitutive model of the artery with damage.

G. A. Holzapfel and T. C. Gasser. A viscoelastic model for ﬁber-reinforced