BN4201 Compilation

Introduction
Tissue = Extra Cellular Matrix (ECM) + cells
4 Main Types of tissues:

Connective Tissue mechanical Support

Epithelial Tissue lining sheets of cells (Mechanically weak)
Muscular Tissue produce force by contraction
Nervous Tissue transfer action potentials

Functions of Soft Tissue

Soft tissues consist of all tissues except for bones, undergo large finite deformation. Examples: skin,

cartilage, blood vessels.

Soft tissues bind, support and protect our body
Soft tissues perform specific mechanical functions
Sometimes they fail and need replacement (need to know their behaviour in the normal env.)
Early signs of diseases are often reflected in soft tissue biomechanics (Diagnosis therapy)

Extracellular Matrix (ECM) defines the form and function of tissues

Major components of the ECM provides strength to cells

Collagen and Elastin are the most important fibre proteins

Collagen

Triple-stranded helical rod

most collagen molecules consist of 3 amino acids
linked to each other by covalent bonds to form collagen fibrils
Type I is most abundant
Intra- and inter- molecular cross links give strength and stability to tissues
main load bearing elements of tissues

Elastin

present as thin strands in tissues

intertwined with collagen
joined together by covalent bonds to form a 3D cross-linked network
sustains large deformations without rupturing (stretched up to 2.5 times initial length)
gives tissues their elasticity (regain original shape)
in contrast to collagen, elastin network does not have a pronounced hierarchical organization

Nonlinearity: Stiffness increases with strain (tested via uniaxial loading applied to soft tissue strips)

Crimp collagen represents their original form

Linear response occurs when all collagen

fibres are straight

Toe Region: physiological range
Linear Region: Won't happen under normal

conditions unless during accidents

e.g. a healthy artery expands alot less
collagen depletion causes a weaker stiffness
response

Anisotropy: stiffness depends on direction (tested via small angle light scattering)

Ligaments are stronger along the longitudinal direction

Transverse mechanical response is linear (almost no collagen

fibres aligned in this direction)

Longitudinal mechanical response is non-linear (more collagen

fibres aligned in this direction)

Collagen fibres reinforce tissues along specific orientations

(highest stress)
Anisotropy is caused by collagen (long), not elastin (short &
coiled)

Biaxial Testing: Anisotropy + Nonlinearity

Different curves: Represent Anisotropy

Different slopes: Represent Nonlinearity

Hyperelasticity

Soft tissues can exhibit large deformations

Hooke's Law is not valid for soft tissues
Finite (large) strain theory needs to be used
Not covered in BN4201

Viscoelasticity (4 types of Time-dependent Mechanical behaviour)

1. Creep
After the intial deformation, the tissue continues deforming at
constant stress which causes the tissue to weaken over time
e.g. people are taller in the morning than in the evening
2. Stress Relaxation
After the initial deformation, the stress experienced by the
tissue continues to decrease at constant strain.

3. Rate Dependency

At increasing strain-rate, tissue gets loaded faster

Soft tissue stiffness is rate dependent
Useful for body to adapt during a dynamic event

4. Hysteresis

Indicates that internal energy is dissipated

during the loading-unloading cycle

Loading phase: Tissue stores energy
Unloading phase: Tissue loses energy to

surroundings
Useful for body to adapt during a dynamic
event

Viscoelasticity is caused by viscous (fluid) and elastic (solid) characteristics

Viscous part dissipates energy, elastic part stores energy

Viscoelasticity helps soft tissues respond to dynamics of mechanical loading
Mechanism: Intermolecular friction between collagen, elastin and proteoglycan polymeric chains
and other complex intermolecular interactions (fluid movement causes viscoelasticity)

Heterogeneity (Different behaviors at different parts of the material)

Example: Arterial Wall
Intima (Inner Layer) consist of epithelial cells and basement membrane
Media (Middle layer) consist of smooth muscle cells, collagen, elastin and proteoglycans
Adventitia (outer layer) consist of fibroblast, collagen and microcapillaries around the blood vessel
Soft tissues are heterogeneous: Stiffness varies spatially
Intima, Adventitia and Media sections all show different
mechanical responses

Adaptive (Tissue behavior changes with time/age)

Nonlinearity, anisotropy, hyperelasticity, viscoelasticity
and heterogeneity constantly change:

Through life (homeostasis)

With pathology (e.g. aneurysms)
With age

Growth and Remodeling example: Arteries exhibit wall thickening in response to increased blood pressure
Why: To reduce stress in the arterial wall (law of laplace, hoop stress)

Muscle Tissues 1
In contrast to other tissues, muscle tissue cells have the ability to contract and convert the chemical energy
of ATP into mechanical energy
Goal is to generate forces and movements used in the regulation of the internal environment and to
produce movements in the external environment.
3 Main types of Muscles
1. Smooth Muscle

Smooth muscle cells have a single nucleus

surround the lumen of blood vessels, urinary and gastrointestinal tracts
Under involuntary control

2. Cardiac Muscle

Makes up majority of heart mass

composed of striated, tubular, branched, and uni-nucleated fibre cells (myocytes)
Under involuntary control

3. Skeletal Muscle

Most abundant tissue in the human body

Usually attached to bones via tendons (transmit load to bones)
Very long cells (up to 30 cm), tubular and multi-nucleated
Usually under voluntary (conscious control)

Skeletal Muscle Function:

Locomotion and positioning of body segments in space

Maintenance of body posture
Stabilisation of joints
Strength and protection to skeleton (by load distribution and absorbing shocks)
Heat generation
Mostly collagen type I. As opposed to
muscles, tendons have no active
contractile properties.
Epimysium: Connective tissue that
surrounds the muscle and protects it from
friction against other muscles and bones.
It connects with tendons.
Perimysium: Connective tissues that
surrounds groups of muscle cells (i.e.

fascicles)
Endomysium: Connective tissue that surrounds each individual muscle cell (muscle fibre)
Forces produced by the contracting muscles are transmitted to bone through the connective tissues (epiperi- endo-mysium) and tendons.
Muscle fibres = Muscle cells = Myofibres

Muscle Fibre: Structural unit of skeletal muscle. Long cylindrical cell with hundreds of nuclei

Consist of many myofibrils, invested by a plasma membrane called the sarcolemma

Cytoplasm of a muscle cell is Sarcoplasm

Myofibrils are composed of 3 types of myofilaments:

Thin filaments: actin (5nm to 8nm)

Thick filaments: myosin (12 to 18 nm)
Elastin filaments: titin (acts like a spring, helps relaxation)

Repeat unit in myofibrils is called a sarcomere (the contractile unit of the muscle fibre). There are hundreds
of myofilaments in 1 myofibril
Sarcomere
A-band:

Thick (myosin) and think (actin) filaments overlap

Strongly Anisotropic (optically)

I-Band

Only thin filaments (actin)

Isotropic (optically)

H-Band:

Only thick filament (myosin)

Z-Line:

Defines sarcomere region

Bisects I-band
Connection between actin proteins

M-Line:

The original lengths of thick and think filaments

are maintained.
Shortening of the I- and H-bands as the Z-lines
move closer to each other. (Sarcomere length
decreases). The A-band (myosin) remains
constant.
Twitch: Muscle fibres contract when all sarcomeres
shorten simultaneously in an all-or-nothing fashion
(due to titin compression)

Connection between myosin proteins

Elastin filament (Titin)

Titin connects the Z-line to the M-line in sarcomeres and is part of myosin.
Contributes to the passive stiffness of skeletal muscles by limiting the range of sarcomere motion in

tension
Stores energy in compressed state
Helps to relax muscle by bringing it back to original shape after contraction
Without titin, muscles fall apart in the relaxed state as myosin heads are not attached to actin in this
state

Thick filaments (mostly myosin) contain several myosin molecules

Each myosin molecule consists of 2 protein chains wrapped around each other with 2 globular
heads pointing outwards

Each globular head contains 2 binding sites: 1 for actin and 1 for ATP

Thin filaments

Attached at either end of each sarcomere

Consist of 3 different proteins: Actin protein (main component), tropomyosin protein, troponin protein
Actin has the shape of a double helix and contains the myosin-binding site where the head of the
thick filament binds to during contraction

Role of Calcium in muscle contraction

Tropomyosin blocks the myosin binding site went muscle is relaxed (no contraction possible)
Each tropomyosin molecule is held in its blocking position by Troponin (a protein bound to both actin

and tropomyosin)
Contraction occurs when calcium ions bind to troponin
Binding of calcium produces a change in the shape of troponin which troponins linkage to
tropomyosin, drags tropomyosin away from the myosin-binding site (myosin-binding site is exposed

and contraction) can occur

Removal of calcium reverses the process

Sarcoplasmic Reticulum

Stores calcium ions

Can pump and release calcium ions when prompted by the T-tubules (not part of the cell)

T-tubules:

Allows the propagation of action potentials from outside the cell into the interior of the cell

Cross-Bridge Cycle
Step 1 : A new cross-bridge cycle begins with the binding of an energised myosin cross-bridge to actin in a
thin filament
Step 2 : The binding of energised myosin (M*) to actin triggers the release of the strained conformation of
the energised cross-bridge, which produces the movement of the bound cross-bridge and the release of
ADP and inorganic phosphate (Pi). ATP binding site becomes free, new ATP can come in. (Power stroke
the myosin head releases energy, tugging the thin filament along)
Step 3 : ATP binds to myosin, causing the cross-bridge to detach from actin
Step 4 : Hydrolysis of ATP energises the cross-bridge. This produces an energised form of myosin (M*) to
which the products of ATP hydrolysis, ADP and Pi are still bound.
In summary, (1) cross bridge attaches to a think filament (actin), (2) cross bridge moves and produces
tension in the thin filament, (3) cross-bridge detached from thin filament, (4) cross-bridge gets energised.
Rigor Mortis

Stiffening of skeletal muscles (begins several hours after death)

After death, the sarcoplasmic reticulum breaks down releasing calcium, which causes a contraction

to occur.
ATP concentration in cells declines after death (due to low oxygen supply).
There is no ATP to unbind thick and thin filaments
Muscles stay contracted until disintegration of muscle tissue

Excitation-Contraction Coupling (sequence of events where action potential leads to cross-bridge activity)

Skeletal muscles never contract unless stimulated by nerves. After an action potential, there is a rapid
increase in cytosolic calcium concentration (due to T-tubules and sarcoplasmic reticulum activation).
Calcium binds to troponin, removing the blocking effect of tropomyosin and allow cross-bridge cycling

Axons of the nerve cells (motor neurons) innervate muscle fibres. They are myelinated for speed.
Upon reaching a muscle, the axon of a motor neuron divides into many branches, each branch forming

a single junction with a muscle fibre.

Each muscle fibre is innervated by only 1 motor neuron
Motor unit: Motor neuron + the several muscle fibres it innervates

Number of muscle fibres forming a motor unit is closely related to the degree of control
For small muscles that perform fine movements (eye movements). Smaller unit = better control
For large muscles that perform coarse movements (biceps). Larger unit = more force
Motor End Plate: Region of the muscle fibre plasma membrane that lies directly under the terminal portion
of the axon
Neuromuscular Junction: Junction of an axon terminal with the motor end plate
Excitation-Contraction Coupling

Axon terminals of a motor neuron contain a neurotransmitter, acetycholine

When an AP arrives at the axon terminal, acetylcholine is released into the extracellular cleft and

then binds to receptors on the motor end plate

This binding allows opening of ion channels to yield an end-plate action potential
Since most neuromuscular junctions are located near the middle of a muscle fibre, this newly

generated AP propagates in both directions towards the fibre ends.

Calcium is released, and contraction occurs

How does relaxation occur?

After calcium ions are released within muscles to cause contraction, special calcium ion pumps get

immediately activated. They are located within the membrane of the sarcoplasmic reticulum.
They pump calcium back-in (requires ATP).
They take a longer time than calcium release, allows contraction to occur for some time after a

single AP.
Net effect is a twitch (a transient contraction of the motor unit)
Relaxation is aided by spring-like action of titin molecules as they uncoil

Skeletal Muscles 2

Each cross-bridge works independently and 1 power-stroke only produces a very small movement

of a thin filament relative to a thick filament.

At any 1 instant during contraction, only a portion of the cross-bridges overlapping a thin filament
are attached to the thin filaments and produce tension

Isotonic Contraction

Constant tension is applied to muscle and length is

recorded during contraction

All 4 steps of the cross-bridge cycle are performed
Muscle changes its length and moves a load

Isometric Contraction

A muscle is held
at constant

length and tension generated by the

muscle is
Tension in the

recorded during contraction

muscle increases but muscle does not

change length
The bound

cross-bridges are unable to move the

thin filaments

because of the load acting on the muscle

fibres, but they

do exert a force on the thin filaments

(isometric

tension)

Isotonic VS Isometric Twitches

Twitch: Mechanical response due to a single AP

After an AP, there is a latent period until tension starts to

increase.
For an isometric twitch, the developed tension reaches a

maximum then declines to the resting state

For an isotonic twitch, there is no muscle motion until enough
force is developed to overcome load. There is an actual period of
isometric contraction before shortening. The higher the load, the
longer the delay

Wave Summation Isometric Contraction

A maintained contraction in response to repetitive stimulation is a tetanus (2 types)

Unfused tetanus: At low stimulation frequencies, tension may oscillate as the muscle fibre partially

relaxes between stimuli.

Fused tetanus: No oscillations are observed at the critical frequency (tetanized state)

Greater the stimulation frequency, the greater the tension

For frequencies higher than critical frequency, further increase in contraction force is very slight

Active Tension VS Length

The amount of active tension developed by a muscle fibre during contraction (and thus its strength) can
be altered by changing the length of the fibre before contraction.
a) When a muscle is highly stretched passively, no overlap between actin and myosin: No tension
b) At optimum length, there is maximum overlap between actin and myosin: maximum tension
c) For lengths less than optimum length, tension decreases because (1) the overlapping sets of thin
filaments from opposite ends of the sarcomere interfere with the cross-bridges ability to bind and
exert force; (2) the affinity of troponin for calcium decreases; (3) distortion of filaments occur for very
short fibre lengths

(Passive + Active Tension) VS Length

Tension VS Shortening Velocity

Muscles shorten more rapidly against light loads than they do against heavy ones
Suppose a muscle is subjected to high-frequency stimulation so that it goes into tetanus. If the muscle
is held isometrically and then suddenly released, the velocity of contraction, V can be measured for
different loads placed on the muscle, P.

Hills Equation

Active contraction Behaviour

Higher the load, lower the contraction velocity

Higher the velocity, the lower is the tension

Passive Viscoelastic Behaviour (opposite behaviour)

At higher strain rates, stiffness increases (higher tension) based on viscoelasticity rate-dependency
graph

Active contraction if a muscle has no resemblance to the viscoelasticity of a passive material

Hills Equation
Found to describe all skeletal muscles including cardiac and smooth muscles. Can be normalised:

Power has a maximum when the force and the

speed are between

a third and a quarter of their maximal values.

Limitation of Hills Equation
It only reveals one aspect of muscle behaviour

Cannot describe a single twitch

Cannot describe a wave summation
Cannot describe the tension-velocity relationship when a tetanized muscle is subjected to a strain

that varies with time

Cannot describe the passive mechanical behaviour of an unstimulated muscle

Tension VS Time (Viscoelasticity)

CE represents the contractile proteins (actin and myosin)

PEC represents the passive elasticity of connective tissues (epi/peri/endomysium) and titin
SEC represents the passive elasticity of the tendon
Only 1 interpretation as this remains a model so it is wrong by definition
(the rest + Skeletal Muscles 3 refer to notes)
Skeletal Muscles 4
Skeletal muscle fibres can be arranged either parallel to the muscle longitudinal axis or obliquely
When the fibres run obliquely to the long axis, the organisation is called a pennate
Unipennate muscles have the tendon running along one side
In a bipennate muscle, the tendon passes up the centre of the muscle and the fibres attached to it

on either side
Multipennate muscles have aponeuroses (layers) of tendon material approaching the belly of the
muscle from both ends, and the fibres run only a short distance from one aponeurosis to another.

Biomechanical advantage of pennate muscle, compared to parallel-fibered muscles (refer to notes)

Skeletal Muscle Fatigue

Muscle fatigue: When a muscle fibre is repeatedly stimulated, the tension developed by the fibre

eventually decreases even though the stimulation continues

Additional characteristics: decreased shortening velocity, and slower rate of relaxation
If a muscle is allowed to rest, it can recover its ability to contract. However, the rate of recovery depends
upon the duration and intensity of the previous activity (and rest period).
o High-intensity, short-duration exercise (weight-lifting): Fatigue with rapid recovery (high-freq. fatigue)
o Low-intensity, long-duration exercise (marathon): Fatigue with slow recovery (low-freq. fatigue)

Muscle fatigue: Not caused by ATP depletion (ATP concentration does not significantly change)
But ATP is depleted without muscle fatigue. Leads to a state (rigor) which is very damaging to muscle
fibres. Muscle fatigue is evolved as a mechanism for preventing the onset of rigor.
Types of Skeletal Muscle Fibres
All of them do not have the same mechanical and metabolic characteristics. Different based on:
(1) Their maximal velocities of shortening (fast or slow fibres)
(2) The major pathway used to form ATP (oxidative or glycolytic fibres)

Fibres containing myosin with high ATPase (enzyme to split ATP to form ADP) activity are classified as

fast fibres, and those with low activity as slow fibres

Rate of cross-bridge cycling is about 4X faster in fast fibres than in slow fibres
Oxidative fibres (red in colour) contain numerous mitochondria (to convert oxygen and nutrients into

ATP). They also contain a large amount of myoglobin (oxygen tank).

Glycolytic fibres (white in colour) have few mitochondria and little myoglobin but possess a high

concentration of glycolytic enzymes and a large store of glycogen.

3 types of muscle fibres exist:
o Slow-oxidative: Type I
o Fast-oxidative: Type IIa
o Fast-glycolytic: Type IIb
Glycolytic fibres generally have much larger diameters than oxidative fibres (good for supporting large
loads)

a) Fast-glycolytic fibres: Fatigue rapidly.

b) Slow-oxidative fibres: Very resistant to fatigue, which allows them to maintain contractile activity for long
periods of time with little loss of tension.
c) Fast-oxidative: Have an intermediate capacity to resist fatigue.

Back and leg muscles: Contain a large number of slow-oxidative fibres to maintain activity for long

periods of time without fatigue (support of posture)

Arm muscles: Contain a large number of fast-glycolytic fibres to produce large amounts of tension
over a short period (lifting of heavy objects)

Muscle Growth & Remodelling

Denervation Atrophy: If the neurons to a muscle die or if the neuromuscular junctions become nonfunctional, the denervated muscle fibres will become progressively smaller in diameter, and the amount
of contractive proteins will decrease.

Disuse Atrophy: Occurs if a muscle is not being used for a long period of time (e.g. broken limb in a

cast), but the nerve supply is intact.

Hypertrophy: Occurs with increased amounts of contractile activity (e.g. through exercise). Increase in
size of the muscle fibres and in their capacity to produce ATP.

With atrophy or hypertrophy, the number of muscle fibres does not change (only metabolic activity and
diameter)

Muscle Growth & Remodelling

Muscular Dystrophy: Genetic disease. Associated with the progressive degeneration of skeletal (and
cardiac) muscle cells, weakening of the muscles, and leads to death.

Exercising weakens dystrophic muscles.

Muscular dystrophy affects the expression of dystrophin thought to be involved with the structural
integrity of the sarcolemma and the ion channels.

Muscle Cramps:
Involuntarily tetanic contraction of skeletal muscles produces muscle cramps
During cramping, nerve APs fire at abnormally high rates
Probably related to electrolyte imbalances in extracelluar fluid surrounding both the muscle and nerve fibres

Clinical Application of Muscle Biomechanics

Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by
skeletal muscles.

EMG signals can be analysed to detect skeletal muscle pathologies.

While an EMG signal reflects contraction and thus active tension, the exact relationship between an
EMG signal and its associated muscle force is poorly understood. (e.g. difficulty in comparing data
from 1 patient to another). No link between electric signal and force generated by muscles.

Several interpretations have been given for the EMG vs Force relationship
(1) Linear or nonlinear relationship between EMG signal (absolute value) and muscle force
(2) Root mean square of the EMG signal is related to muscle force
(3) Mean or median frequency of the EMG signal is related to muscle force
Additional problems with EMG

The amplitude of the EMG signal is affected by the location of the electrode
Electric potentials from other nearby muscles may also reach the recording site thus contributing to

the recorded EMG signal. This is referred to as crosstalk.

Crosstalk can be filtered but cannot be fully avoided.

In Vivo Measurements of Muscle Deformations

3D skeletal muscle strain due to contraction can be measured in vivo using Magnetic Resonance Imaging
(MRI) and Image processing.
In Vivo Measurements of Muscle Fibre Direction
Muscle fibre direction can be obtained in vivo using Magnetic Resonance Diffusion Tensor Imaging (MRDTI)

Tendon & Ligament 2

Role of tendons:

Attach muscle to bone

Transmit tensile forces from muscle to bone
Act as dynamic restraint
Enable the muscle to be at an optimal distance from a joint without requiring an extended length of
muscle

Role of ligaments (which connect bone to bone):

Augment the mechanical stability of joints

Guide joint motion
Prevent excessive motion
Act as static restraints (prevent excessive motion)

Composition and Structure of Tendon & Ligaments

Share structural and mechanical characteristics

Do not have the ability to contract (unlike muscles)
Are dense connective tissue structures known as parallel-fibered collageneous tissues
Are sparsely vascularised (have very few blood vessels)
Consist of relatively few cells (fibroblasts) and of an abundant ECM
ECM primarily composed of collagen (main component), elastin fibres, and proteoglycans (to resist

compression)
Will return to their original length when unloaded (due to elastin)

ECM is responsible for viscoelastic properties. Collagen is responsible for stiff-response. Tendons are stiffer
than muscles.
Some specialised ligaments contain a large amount of elastin to limit ligament buckling during extension of
the spine.
Fibroblast

Most common type of cells found in tendons and ligaments

Synthesize(or replace) the ECM components (collagen, elastin or glycosaminoglycans, etc)
Align longitudinally along collagen fibre bundles
Monitor the mechanical environment and produce proteins in response to local mechanical stimuli
for maintenance and repair (Important in growth and remodelling)

Nonlinearity of Tendons & Ligaments

For ligaments, stress-strain nonlinearity (stiffening) protects the joints from excessive relative

movements between bones

For tendons, nonlinearity ensures efficient load

transfer from muscle to bones.

Tendons are usually stiffer than ligaments

The
tangent modulus vs stress relationship is also valid to model the passive mechanical behaviour of skeletal
and cardiac muscles.
Recruitment of collagen fibres: One by one start contributing to resistance (recruited at different times).
Collagen fibres have different length (provide resistance at different displacement).

Anisotropy for Tendons & Ligaments

Collagen fibre organisation differs in tendons and ligaments and is suited to the function of each. Larger
stiffness response in longitudinal direction for both. Collagen alignment is more messy for ligaments.
Tendons: Must provide high tensile strength and stiffness to transmit muscle forces to bone (as fast as
possible) without substantial deformation. The highly orientated parallel fibre bundles provide the high
tensile strength and minimal extensibility.
Ligaments: Must provide high tensile strength but since they need to maintain exoskeleton stability, they
may experience off-axis loads and therefore require some strength in off-axis direction.
Viscoelasticity for Tendons and Ligaments

General Kelvin Solid model consists of 1 spring element with n

Maxwell elements in parallel.

The stress relaxation behaviour of the General Kelvin Solid is

Such a model offers many parameters and a better fit.

However, there are several sets of parameters that would give the
same stress response (uniqueness problem). 2 sets of different

values giving the same curve.

The number of parameters can be reduced to 3 if we take n =
infinity

During walking or jogging, cyclic stress relaxation occurs,

in

which the peak stress within the tissue decreases with

each

cycle. This trend could help prevent fatigue failure of

tendons and ligaments.

Tendon & Ligament 3

Both tendons and ligaments are surrounded by loose connective tissue (paratenon) consisting

mostly of collagen and elastin.

The paratenon forms a sheath that protects the tendon/ligament and reduces friction with

neighboring tissues.
In location where tendons are subjected to particularly high frictional forces (e.g. at the level of wrist

joint), a synovial membrane (epitenon) is found just beneath the paratenon.

Synovial fluid is produced by the synovial cells of the epitenon to reduce friction.

Insertion into Bone

Structure of the insertions into bone is similar in tendons and ligaments and consist of 4 zones.
At the end of the tendon (zone 1), the collagen fibres intermesh with fibrocartilage (zone 2) - a

cartilage rich in Type I collagen fibres.

This fibrocartilage (zone 2) gradually becomes mineralised fibrocartilage (zone 3) and then merges

into cortical bone (zone 4).

The change from more tendinous to more bony material produces a gradual increase in tissue
stiffness thought to decrease stress concentrations that would be detrimental and could yield disinsertion.

Vascularisation

Tendons and ligaments have a limited vascularisation (more blood vessels make tendons and

ligaments mechanically weaker), which affects directly their healing process and metabolic activity.
Tendons receive their blood supply directly from vessels in the perimysium (connective tissue that
surrounds group of muscle cells), the bone insertion, and the surrounding tissue via vessels in the

paratenon.
Vessels enter the tendon from many points with a longitudinal system of capillaries.

Growth & Remodelling for Tendons & Ligaments

They remodel in response to the mechanical demands placed on them. Become stronger and stiffer

when subjected to increased stress, and weaker when stress is reduced.

Immobilization (body cast) has been found to reduce the biomechanical properties o the bone-

ligament complex.
Immobilized ligaments displayed more elongation and significantly less stiff.
After immobilization, there is an increase in immature collagen and a decrease in the amount and

quality of cross-links within and between collagen fibrils.

Decrease in cross-sectional area of ligaments after immobilization (collagen degradation)

Ageing

During maturation, the number and quality of intra- and inter- molecular collagen cross-links
increases, resulting in increased tensile strength of the tendon and ligament. An increase in

collagen fibril diameter is also observed.

Collagen fibril diameter decreases remarkably in the elderly (contributes to a decrease in stiffness

with age).
However, ageing is associated with an increase in collagen cross-links in the elderly and an
increase in brittleness of the collagen fibrils (contributes to an increase in stiffness with age).

Ageing is associated with more injuries (rupture at smaller strain)

Injuries

Mechanisms are similar for both tendons and ligaments

Injuries from high rotational torque (increases tensile loads)
Injuries from overuse (subjected to high strain rate during frequent loading cycles and insufficient
time is allowed for healing process).

Tendinopathy

Describes a variety of painful conditions that develop in and around tendons in response to overuse
Associated chronic diseases include disorganization of collagen fibres, increased cellularity,
inflammation, tendon swelling, loss of mechanical properties, pain, increase in production of MMPs

(degrading ECM enzymes), fibroblast apoptosis.

Net result is tendon degeneration, weakness, tearing an pain
Age and environmental factors (diet & smoking) contribute to the development of tendinopathy.

Can be detected by:

Ultrasound Imaging
Magnetic Resonance Imaging

Grafts

Reconstruction of torn ligaments

Allograft: From different individuals of the same species
Autograft: From the same individual
Achilles tendons are usually used as allograft tissue. Parts of the patellar tendon or Hamstring

tendon are commonly used as autograft.

Replacement tissue may undergo considerable biomechanical remodelling, material properties may
not always return to normal levels.

True for vein grafts to replace damaged arteries, vein grafts will remodel and slowly turn into arteries
Artificial ligament grafts (polyester) are not adaptive.

How to measure tendon/ligament biomechanics in vivo?

Using an ultrasound technique: Shear wave elastography (supersonic shear imaging)

Ultrasound energy is focused at one point in the tissue (create force in tissue by making it vibrate),
which elicit the propagation of a shear deforming wave in a direction perpendicular to that of

imaging.
The elastic modulus (tangent modulus) is proportional to the speed of propagation.

Measuring Tendon Anisotropy in-vivo using Shear Wave Elastography

Tendon Anisotropy can be measured in vivo if the probe is rotated at different angles to acquire data
(1) in the plane of the fibres and (2) in the plane perpendicular to the fibres (by shifting probe 90
degrees).

Measuring Tendon Nonlinearity in-vivo using Shear Wave Elastography

Tendon Nonlinerity can be measured in vivo if the tendon is imaged at different degrees of stretch.
Different positions have different degrees of stretch.

Advantages of Shear Wave Elastography (SWE)

Useful to detect local defects in tendons (decrease in tangent modulus ), to characterise injuries,
manage recovery following injuries, and guide treatments.

Limitations of Shear Wave Elastography (SWE)

It is a 2D technique. Since tendons and ligaments are highly anisotropic, a difference of a few
degrees in the positioning of the ultrasound probe can be responsible for significant differences in

measurement.
Difficult to achieve different grades of flexion (to assess nonlinearity) in patients with local pain (not

ethical).
SWE cannot provide stress or strain measurements (can only give stiffness). However, SWE
measurements could e used in patient-specific biomechanical models (e.g. finite element models) to
predict pathologies.

Cartilage 1

Exist on the articulating surfaces of synovial joints

Dense layer of fibrous tissue covering articular surfaces of bones in synovial joints
Withstanding a highly loaded joint environment without failure during an average lifetime
An isolated tissue, devoid of blood vessels
Nourished and drained only by diffusion and convection from surrounding synovial fluid
Lowest cell density of all tissue

Cartilage Function

Distributes joint loads over a wide thus decreasing the stresses sustained by the contacting joint

surfaces
To allow relative movement of the opposing joint surfaces with minimal friction and wear
Synovial fluid (between opposing cartilage layers) acts as a lubricant and reduces the coefficient of
friction

Cartilage Composition
Chondrocytes:

Sparsely distributed cells (less than 10% of the tissue's volume)

Manufacture, secrete, organize and maintain the organic component of the ECM
Isolated and nourished through diffusion of substances
Surrounded by a protective cover of pericellcular matrix and capsule, believed to protect them from
excessive stresses and strains during cartilage compression

Cartilage ECM:

Dense network of collagen fibrils (Type II) (trap proteoglycans and has a different stiffness from

Type I), enmeshed in a concentrated solution of proteoglycans.

Remaining 60-85% is water, inorganic salts, other matrix proteins, glycoproteins and lipids
Content and structure of collagen and proteoglycans in articular cartilage vary with depth from

articulating surface.
Collagen fibrils and proteoglycans are the structural components supporting the internal mechanical

stresses that results from loads being applied to cartilage.

Collagen fibrils, proteoglycans, water (provide resistance to compression) determine the
biomechanical properties of cartilage

Collagen provides support for other articular cartilage components

Type II collagen provides tensile strength (but not compressive strength) for articular cartilage
Proteoglycans

Large protein-polysaccharide molecules composed of a protein core to which 1 or more

glycosaminoglycans (GAGs) side chains are attached

Bind to Hyaluronic Acid to form large Proteoglycan Aggregates
Side-chains contain negatively charged molecules that repel each other
Mutual repulsion of these negative charges causes an aggregated proteoglycan molecule to spread
out and occupy and large volume

When the cartilage is compressed, the negatively charged sites on proteoglycans are pushed closer
together, which increases their mutual repulsive force and add to the compressive stiffness of

cartilage
PG aggregation promotes immobilisation of PGs within the fine collagen meshwork adding
structural stability and rigidity to the ECM

Water (most abundant component)

Most concentrated near articular surface ad decreases linearly with depth.

Essential to the health of avascular cartilage cartilage as it permits gas, nutrient, and waste product

movement back-and-forth between chrondrocytes and nutrient-rich synovial fluid

Water can flow out of cartilage tissue with applied pressure
The permeability of articular cartilage is low, which helps retain water within the collagen matrix

when it is compressed
Retention of fluid and its pressurisation with compression of the tissue allows cartilage to support
large compressive loads (protects cells + ECM from a high stress/strain environment)

Cartilage Microstructure
Structurally heterogeneous: biomechanical properties change as a function of depth (4 zones)

1. Superficial Tangential Zone (10-20% thickness): Organisation of collagen fibres parallel to the

surface (high anisotropy) helps to resist shear forces generated by joint movement
2. Middle Zone (40-60 thickness): Random collagen fibre organisation (isotropy) helps trap

proteoglycans
3. Deep Zone (30-40% thickness): Collagen fibres come together, forming larger, radially orientated

bundles. Perpendicular fibres (with high anisotropy) allow cartilage to anchor to underlying bone.
Tidemark: Interface between articular cartilage and calcified cartilage

Arrangement of Chondrocytes

Superficial Tangential Zone: Oblong with their long axes aligned parallel to the articular surface
Middle Zone: "round" and randomly distributed
Deep Zone: Chrondrocytes are arranged in a columnar fashion orientated perpendicular to the
tidemark, the demarcation between the calcified and non-calcified tissue.

Mechanical Role of Molecular Components

Collagen: Resist tensile stress

Proteoglycan: Resist compressive stress
Water: Resist compressive stress

Articular cartilage forms a porous-permeable, fibre-reinforced composite matrix possessing all the essential
characteristics of a solid that is swollen with water and ions and tht is able to resist high stresses and
strains of joint articulation.
Biphasic
Two incompressiable phases:

Interstitial Fluid Phase: Water

Porous-permeable Solid Phase: ECM

Viscoelasticity of Articular Cartilage

Can be mechanically tested in tension (to assess collagen resistance) or in compression (to assess

PGs/GAGs/Water resistance)
3 Common techniques: (1) Confined Compression, (2) Unconfined Compression, (3) Indentation

Confined Compression of Articular Cartilage

A cylindrical cartilage specimen is fitted into a cylindrical, smooth-walled container

No radial deformations are possible
The amount of compression equals the volume of fluid loss because both the water and ECM are

each intrinsically incompressible

Advantage: Creates 1D flow and deformation fields. There is no dependence on radial properties,
and therefore no influence from tissue anisotropy.

Origins of Viscoelasticity in Tissues

Tendons & Ligaments: Viscoelasticity is a result of internal friction caused by the motion of the long

polymeric chains sliding over each other

Bones: Viscoelasticity is caused by the relative slip of lamellae within osteons along with the flow of

the interstitial fluid

Articular cartilage: Viscoelasticity is caused by the flow of interstitial fluid within the porous ECM and

by the frictional drag associated with this flow

Linear viscoelastic models (e.g. Generalised Kelvin Solid) fail to capture the biomechanical
behaviour of articular cartilage and biphasic theory needs to be used to take into account fluid
movement within and out of ECM

Biphasic Compressive Creep Response

Creep is caused by exudation of water

Water exudation is most rapid initially then

diminishes gradually
Creep stops when the compressive stress developed within the solid matrix is sufficient to balance

the applied stress alone. No fluid flow & equilibrium strain is reached
Time taken to reach equilibrium varies inversely with the square of the cartilage thickness
Under high loading, 50% of water may be exuded but this is fully recoverable when stress is

removed
Rate of creep is governed by that of fluid exudation, experimental data can be used to measure

tissue permeability
At equilibrium, no fluid flow occurs, and thus equilibrium deformation can be used to measure the
stiffness of the collagen-PG solid matrix alone.

Direct Measurement of Cartilage Permeability

Permeability in cartilage indicates the resistance to fluid flow through the ECM

Darcy's Law states that the aveage fluid velocity (v) through a soil sample (or cartilage) is
proportional to the pressure gradient. The constant proportionality (k) is called the permeability.

The pressure gradient is approximated by:

Direct Measurement of Cartilage Permeability

Permeability varies with tissue deformation

Under increasing compression, cartilage's permeability will decrease (protective mechanism). Stops

fluid from flowing out to resist higher compression

Deformation-dependent permeability may be a valuable-mechanism for maintaining load sharing

between the solid and fluid phases of cartilage

If fluid flowed easily out of tissue, then the solid matrix would bear the full stress (more prone to
failure)

Biphasic Compressive Stress Relaxation Response (Compressive Behaviour)

Biphasic Stress Relaxation Test (confined compression): A constant compression rate is applied to
the tissue (stress increases) until a fixed displacement u0 is reached and maintained (stress

relaxation to reach an equilibrium.

Loading phase: Applied constant displacement (water needs time to flow out)
Stress-Time graph: Initially high stiffness because water needs time to come out. Easier to

compress after water flows out

Stress rise in the compression phase is associated with fluid exudation, while stress relaxation is
associated with fluid redistribution within the porous solid matrix

Nonlinear Cartilage Behaviour in Tension (Tensile Behaviour)

The biomechanical behaviour of articular cartilage in tension is nonlinear due to the presence of

Type II collagen fibres.

Articular cartilage also exhibits viscoelastic behaviour in tension due to internal friction of the ECM

components (same as ligament & tendons)

Articular cartilage anistropy in the superficial zone follows a radial pattern (prevents expansion)
In tension, articular cartilage is strongly anisotropic. Being stiffer and stronger for specimens
harvested in the direction parallel to the 'split line' pattern (along collagen fibres).

Heterogeneity of Articular Cartilage

Highly Heterogeneous (in tension and

compressive behaviour)

A correlation was found between the

compressive modulus of articular cartilage
(under

creep

behaviour)

and

its

glycosaminoglycan (GAG) content. (More

GAG, more compressive resistance)

Proteoglycans

(and

thus

GAGs)

are

inhomogeneously distributed throughout

the matrix, with their concentration being
the highest in the middle zone and lowest

in

the superficial and deep zones.

Cartilage Growth & Remodelling
Aggrecan synthesis is elicited when cartilage is cyclically compressed. GAG content is increased and so is
the compressive modulus of cartilage
Osteoarthritis (OA)

Degradation of joints, including articular cartilage and subchondral bone

Chronic disease and early symptons cannot be detected since cartilage is aneural
Associated with cracking, fibrillation and wear of articular cartilage
OA depends on a combination of factors including age, sex, heredity, etc.
In OA, there is a decrease in the compressive modulus and an increase in permeability of articular

cartilage (more water flows out, less resistant to compression)

Bone needs to thicken to pick up load (remodeling of trabecular bone). Vascular invasion of calcified
cartilage

Ageing and Osteoarthritis (OA)

Tensile strength of the superficial zone increases with maturation to reach a maximum value at 30

years of age
Thereafter, cartilage's tensile strength decreases with increasing age
Age-related biomechanical changes may contribute to cartilage degeneration in OA

Repeated Loading & Osteoarthritis

Repeated Tensile Loading (Fatigue): Lowers tensile strength of articular cartilage
Repeated Tensile loading may contribute to development and progression of OA

Ocular Biomechanics 1

Important of Vision

Blindness (Most
Vision Loss is a

feared disability)
serious problem (Increased risk

of injuries, loss of

independence, etc.)

Glaucoma

Ocular disorder
Irreversible blindness
Damage to the optic nerve head
Increase in intraocular pressure (IOP) increases risk of glaucoma

Lamina Cribrosa

Attached to the sclera at the optic nerve head

Very porous (mechanically weak)
Mostly collagen fibres + some blood vessels

Hypothesis

Optic nerve head biomechanics indicates a patient's susceptibility to glaucoma

Ocular Hypertension = Stiff ONH
High pressure (due to high IOP) at the ONH causes glaucoma
Normal ONH deformations = No glaucoma
Normal Tension Glaucoma = Weak ONH (at normal IOP)
High ONH deformations = Nerve Cell Death (Shear cells and axons)

Laplace's Law: Perfect Sphere (Thin Wall)

Limitations:

Valid only for simple geometries (perfect sphere). Eye is not a perfect

sphere
Simple materials (isotropic, homogenous, linear and elastic). Eye tissues have none of these
properties.

Finite Element Method: IOP-induced Strain

Increasing pressure increases strain

Increasing modulus reduces strain
Increasing thickness reduces strain
A bigger eye increases strain

Limitations:

Geometry is considered idealized

Connective tissues (sclera and lamina cribrosa) are modeled as isotropic, homogenous and linear
elastic.

Sclera Anisotropy: Idealized Finite Element

Circumferential: Most deformation is along

transverse direction (but LC unaffected)

Helicoidal: Sclera twist. Bad for LC (alot of

shear)
Meridional: LC will stretch alot

Nonlinearity Measurements (Sclera)

Measured by using Electronic Speckle Pattern Interferometry

Eyeball is inflated and 3D scleral displacements recorded in x, y, z displacements at different
pressures.

Nonlinearity Sclera Changes with Glaucoma

Early Glaucoma: Glaucoma eye is less stiff

Moderate Glaucoma: Glaucoma eye gets alot
stiffer to prevent further damage

Sclera Nonlinearity

Sclera is nonlinear (collagen Type I - 90% of dry weight)

Sclera stiffness changes are present at the earliest stages of glaucoma
Important to develop techniques to detect such stiffness changes in vivo

Sclera Heterogeneity

Thickness: Sclera is thicker towards the ONH

Effect Elastic Modulus: High elastic modulus at areas of low thickness
Structural stiffness is obtained by multiplying thickness and elastic modulus

Measuring In-Vivo Biomechanics

Optical Coherence Tomography (OCT): Digital Volume Correlation/Digital Image Correlation

Two different images are captured and compared at different situations

Therapy for Glaucoma

Sclera Stiffening: Chemical injected at the back of the eye.

Keratoconus

Microstructural disorder of the Cornea: Cornea bulges out due to collagen disorganization in the

cornea
Current Therapy: Collagen cross-linking of the cornea

Retinal Detachment

Fluid applies more force to the tear

Current Therapy: Sclera Buckling Surgery. Ring is placed to squeeze the eyeball to push retina back
to place. Bad idea as it causes glaucoma

Myopia: Biomechanical Disorder of the Sclera

In myopia, the eye elongates and the sclera weakens.

High myopia can lead to retinal detachment and glaucoma (myopic eye is weaker, lower stiffness)
Current therapy: None. LASIK surgery does not stop the progression of Myopia

Blood Vessel Biomechanics 1

3 Main Types of Blood Vessels:

Arteries
Veins
Capillaries

Mechanical Environment of an Artery

Mechanotransduction: Cells inside blood vessels

react to fluid forces and transform these forces into
chemical responses

Blood vessel experiences cyclic circumferential stress due to

blood pressure
Experiences Axial stress due to blood pressure
Experiences Normal stress perpendicular to the Endothelial cell surface due to blood pressure

Veins

Sustain much smaller pressure

Diameter much thinner
Presence of valves to limit backflow of blood

Capillaries

Smallest blood vessels

Enable the exchange of oxygen, carbon dioxide, nutrients because they are very thin
Red blood cells (high deformability) can squeeze through capillaries

Kinetics of Vein Graft Hyperplasia: Association with Tangential Stress

Vein graft used to replace a damaged artery:

Mechanical properties of vein changes over time to
match that of artery. Stress in the vein graft is
decreasing over time, eventually becomes similar to
stress in artery. (Graft gets thicker over time)

Limitation of Laplace Law:

the

Valid only for simple geometries (perfect cylinder)

Valid only for simple materials (isotropic, homogeneous, linear and elastic). Not for soft tissues.

Nonlinearity: Biomechanical Testing

Nonlinear behavior of arteries.

Multiple curves: Arteries are loaded under different forces

At certain levels of force, artery does not elongate when

we

increase pressure (vertical line graph). This phenomenon

limits deformation of arteries in the body.
Anisotropy: Finite Element Simulations

Tube-like artery subject to axial stretch and internal

pressure
Collagen fibers as the main load bearing constituent of

the

extracellular matrix adapt their orientation and align with respect to the principal stress directions
(maximize strength) in order to minimize wall stress
Residual Stresses

Stress that exists in the body in the absence of

external forces
Are thought to develop in growing arteries so as
reduce stress gradients across wall thickness

Artery opens up after cutting due to residual stress

(presence of internal forces). After elastin is removed,
opening decreases. Thus, elastin is responsible for
internal stresses
Residual Stresses

Without Residual stress: Strong stress gradient

With Residual stress: Low stress gradient

Residual stress tries to keep artery close

Pressure tries to push artery open
Both of them oppose each other

Aneurysms: Disorder of the Artery

Normal abdominal aorta has a much higher tensile

strength and higher maximum strain than AAA.

AAA has a lower maximum strain and tensile
strength

ECM Synthesis in AAA

SMCs and fibroblasts in AAA wall can synthesize ECM components

to

Studies have shown both accelerated and reduced collagen and elastin synthesis (conflicting

studies) in the AAA wall as compared to healthy aorta

Spatially variable: Increased in some areas, decreases in others

ECM Degradation in AAA

Degradation occurs via specific proteolytic enzymes: Matrix Metalloproteinases (MMPs) and

Plasminogen activators (PAs)

SMCs, fibroblasts and macrophages can synthesize MMPs and PAs
Studies have shown both accelerated and reduced synthesis of MMPs and PAs (and their inhibitors)

in the AAA wall as compared to healthy aorta.

Spatially variable: Increased in some areas, decreases in others

Blood Flow Disruption: Thrombus Formation

At the vortex, velocity is not very high so

things can accumulate there. A blood clot

is

created there due to low velocity and

thus low shear stress.

Blood Flow Disruption: Thrombus Formation

The stability and integrity of the aortic wall depends on a normal supply of oxygen.
A thrombus is commonly found in AAA and can serve as a barrier to oxygen flow from the lumen to

the inner layers of the aortic wall (outer layers are supplied by the vasa vasorum)
This may cause hypoxia and result in further ECM degeneration
At blood clot region, endothelial cells do not get blood supply (blocked by thrombus).

Predicting AAA rupture

The local strength of the AAA wall may be adequately predicted by certain clinical, non-invasively
measurable variables (thrombus size, patient's age, gender, etc..) using multiple linear regression

techniques.
Stress (obtained from finite element simulations) can be estimated non-invasively to predict rupture.

A better index should contain both non-invasive estimates of wall strength and wall stress

AAA progression and rupture is better predicted by the RPI than by any other parameter alone
Such technique might improve the clinical management of patients with AAA by optimizing the timing for
reparative intervention.

Bone Biomechanics 1
Function of bones:

Provides structural support for all other components of the body

Provides a framework for motion (muscles to pull something rigid)
Offers protection from impacts, falls and other trauma
Acts as a calcium repository
Houses the marrow (tissue that produces blood cells from stem cells

Composition of Structure of Bone (ECM)

Bone consists of cells embedded in an ECM

Bone ECM contains not only an organic collagen-based phase, but also a unique inorganic material

phase (hydroxyapatite)
Inorganic component makes bone hard and rigid
Organic component gives bone its flexibility and resilience

Bone composition differs depending on location, age, dietary history, presence of diseases, etc.
Bones have 3 types of cells:

Osteoblast: Bone-forming cells (secrete ECM). Located on the surface of bone, build bone to

surround themselves, stabilise to become osteocytes.

Osteoclast: Bone-removing cells (remove bone tissues by removing its mineralised matrix and

breaking up the organic core. Found in pits (called resorption bays) on the bone surface.
Osteocytes: Trapped (still active) osteoblast in the bone ECM matrix they secreted. Thought to be
mechanosensor cells that control the activity of osteoblasts and osteoclasts.

Types of Bones:
Cortical (compact) bone and Trabecular (cancellous or spongy) bone
Porous trabecular bone lies within the shell of the dense cortical bone. Porosity allows more blood
vessels and bone marrow.
Cortical Bone

Fundamental structural unit of cortical bone is the osteon (or Haversian system)
Centre of osteon: Haversian canal that contains blood vessels and nerve fibres
An osteon consists of lamellae of mineralised matrix surrounding the canal
Lacunae are small cavities each containing 1 osteocyte (trapped in lacunae)
Canaliculi are radiating canals reaching the Haversian canal
Cell processes extend from osteocytes into the canaliculi, allowing nutrients from blood vessels in
the Haversian canal to reach the osteocytes

Trabecular Bone

Generally exist only in the confines of the cortical bone coverings

In contrast to cortical bone, the matrix of trabecular bone is an organised 3D porous network of

interconnected struts called trabeculae.

Pores within the trabeculae are filled with bone marrow

Because of its higher porosity, trabecular bone is weaker than 'solid' cortical bone, but it is much

lighter
There are seldom blood vessels within the trabeculae, but there are vessels immediately adjacent to
the tissue.

Differences between soft tissues and hard tissues (Bone)

Bone is linear in the physiological range.

Bone is elastic as opposed to hyperelastic (does

undergo large deformations)

Bone is passive (does not create their own forces)

not

Linear Elasticity for Cortical Bones

Physiological range: cortical bone is a linear elastic

material and can be described with Hooke's law of
elasticity (usually same elastic modulus in tension

and

compression)
Cortical bone is strongest in compression, weakest

in

shear and intermediate in tension

Plastic region: Deformation cannot be recovered

Linear Elasticity for Trabecular Bones

Physiological range: trabecular bone exhibits

linear elastic behaviour in compression

The following region (plastic collapse)
corresponds to the progressive collapse of the

trabecular (trabeculae beams break down)

Once all pores have been eliminated (through
collapse),

the

(densification).

stress

increases

Trabecular

bone

again

becomes

compact bone.
With such protective process, large amounts of energy can be absorbed from impact without
generating high stresses (similar to foam packaging)

Predicting Elastic Modulus with Density

A bone specimen with a relative density more than 0.7 is considered cortical bone
(minor presence of porosity). Trabecular bone has relative density less than 0.7 (it
can approach 0.05).
The apparent density of trabecular bone can be used to predict the
apparent elastic modulus of trabecular bone
Bone exhibits small deformations in vivo (about 0.0025 strain)
Cortical Bone Anisotropy

Cortical bone is both stronger and stiffer when

loaded along the longitudinal direction

Adapted to resist uniaxial loading during habitual
activities such as gait

Cortical bone can be considered as a transverse

isotropic material (same as tendons & ligaments).
Isotropic only in the transverse plane but entire bone is still anisotropic. Perpendicular to the cortical
bone, stiffness is the same in every direction.

Trabecular Bone Anisotropy

Trabeculae must be aligned to resist principal stress directions in trabecular bone.

Anisotropy patterns can be obtaine in trabecular bone using an image processing technique known
as mean intercept length applied to micro-CT images

Bone Viscoelasticity

The stiffness and strength of both cortical and

trabecular bone is strain rate dependent (both

compression and tension)

In the physiological range (strain rates of 0.001 to
0.03/sec), this dependency is weak: both strength and
stiffness are proportional to the strain rate raised to the

power.
At very high strain rates (>1/sec) can represent
trauma. Increased strength and stiffness is
advantageous for such scenarios

0.06

Viscoelasticity in bone is caused by the relative slip of lamellae within the osteons along with the
flow of the interstitial fluid.

Bone Heterogeneity

Differences in mechanical behaviour between

trabecular and cortical bone (in compression)

can

be observed. (Different stiffness)

Bone Growth and Remodelling

Like any soft tissue, bone has the ability to

remodel, by altering its size, shape, and structure, to meet the mechanical demands placed on it.
Bone adapts its structure through the responsivenes of bone cells to local mechanical stimuli

(mechanotransduction) from osteocytes.

Wolff's Law: Bone senses and adapts to its mechanical environment
Bone Remodeling: A life long process where old bone is removed from the skeleton (bone

resorption) and new bone is added (ossification or bone formation).

Example: Humeral Hypertropy in response to exercise
Example: Atrophy. An implant can be used to heal a fracture bone. The implant carries high loads
and 'unloads' the bone to great extent. The bone may atrophy in response to diminished loads

Measuring Anisotropy in Trabecular Bone

The mean intercept length (MIL) is used in bone biomechanics
estimate local anisotropy in trabecular bones. The MIL is average distance, measured along a particular
straight line, between 2 bone/marrow interfaces. In 2D, the MIL is a function of the angle theta and can
describe tissue anisotropy.

to