Lecture 10

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BME 322

Biomechanics of Articular Cartilage


Introduction

• There are three types of joints in the human body


• Fibrous (fixed or immovable, ex/joints in the skull)
• Cartilaginous (more movable than fibrous but with
limited degree of freedom, ex/ spine)
• Synovial or diarthodial (allow a large degree of
motion, example knee, hip, elbow, shoulder)
Cartilage
There are three types of cartilage in the human body. They are similar embryologically
and histologically but have different mechanical and biochemical properties

3
Articular Cartilage

Synovial joints are the only type of joint


which allows high degrees of
movement.
The joint itself is defined by the synovial
sac between the articulating bones, but
the bones themselves are also covered
with a thin layer of material called
articular cartilage (sometimes hyaline
articular cartilage).
Articular Cartilage
This is a thin (1-6mm) layer of tissue
that covers the ends of the bone. It is
unusual as tissues go:
• It has no blood vessels
• It has no lymphatic vessels
• It has no nerves
• It is immuno-privileged
• And it has the lowest cell density in
the body.
Its function is to distribute the load at
the bone ends, and reduce friction.
Articular Cartilage
• Rather than being composed primarily
of cells, cartilage largely consists of a
cross-linked matrix of the protein
collagen in a solution of
proteoglycans.
• Chondrocytes (cartilage-producing
cells) make up only 10% of the
cartilage.
• Since there is no blood supply to the
cartilage, chondrocytes receive
nutrition from the synovial fluid which
is distributed through the tissue by
mechanical compression.
Articular Cartilage
• Chondrocytes are there to repair damage
to the extracellular matrix by production
of new collagen.
• Articular cartilage is divides into three
zones:
The superficial tangential zone has dense
fibres parallel to the surface
The middle zone has fibres that are more
dispersed and randomly oriented
The deep zone has fibres oriented at right
angles to the connecting surface
Structure of articular cartilage
• Given the low cell density, what is
articular cartilage made of?
Aggrecan
• Three main components: Hyaluronan

Interlinked Collagen fibrils Interstitial fluid


Hyaluronans (made of hyaluronic Collagen fibril
acid) to which are attached
aggrecans (Proteoglycans, PGs,
and Glycosaminoglycans, GAGs) Attached aggrecan

Water (and dissolved ions)


Collagen: The name collagen comes from the Greek, with the prefix
kólla, meaning “glue", and suffix -gen, denoting "producing"

• Collagen is the one of most abundant


protein in the human body
• In cartilage, collagen has a high level
of structural organization providing a
fiberous ultrastructure.
• The fundamental biological unit of
collagen is Tropocollagen
• Tropocollagen is made from three
procollagen polypeptide chains (alpha
chains)
Collagen

• Three alpha chains are further coiled into a


right-handed triple helix forming the
tropcollagen molecule.
• This rod-like molecule is 300 nm long and
has a diameter of 1.4 nm
• The molecules polymerize into collagen
fibrils (dia = 25-40 nm)
• Three polypeptide chains alpha chain
Triple Helix (3 alpha chains)
Tropocollagen molecule collagen fibrils
collagen fibers collagen bundles
Collagen: Biomechanical Properties
• Collagen in cartilage is inhomogeneously distributed

• Has a high tensile stiffness and strength, but is weak


in compression

• Highly anisotropic (its properties differ with the direction


of loading): Attributed to collagen fibre arrangement,
cross-link density, collagen-PG interactions

In tension, anisotropy is described


with respect to the direction of the
articular surface split lines.

The origin of the pattern is related to


the directional variation of the tensile
stiffness and strength characteristics
of articular cartilage.
Proteoglycan (PGs)
• Large protein-polysaccharide molecule,
composed of a protein core to which one or
more glycosaminoglycans (GAGs) are
attached

• Not homogenously distributed in collagen:


• Highest concentration in middle zone
• Lowest concentrations in superficial and
deep zones

• Adds stability and rigidity to ECM (Extra


cellular Matrix)

• Proteoglycans stick to one another to form


supramolecular structures called “aggrecans”.
These in turn stick to hyaluronic acids to
form “bottle brush” structures.
Water
• Most abundant component of cartilage

• Most concentrated near articular surface

• Contains free mobile cations (e.g. Na+, K+, Ca2+)

• Allows movement of gas, nutrients, waste products

• Its movement influences cartilage mechanical behavior.

• Essential to the health of this avascular tissue, as it permits gas, nutrient, and waste product movement
between chondrocytes and the surrounding nutrient-rich synovial fluid

• Most of the water occupies the interfibrillar space of the ECM and is free to move when a load or
pressure gradient are applied to the tissue.

• When loaded by a compressive force, approximately 70% of the water may be moved: important in
controlling cartilage mechanical behavior and joint lubrication
Mechanical properties of
articular cartilage
Cartilage Functions at Multiple Scales
Mechanical behaviour of articular cartilage
• The biomechanical properties of
cartilage are unusual – which derives
from its composition of two distinct
phases (Biphasic) a solid phase
(collagen/PGs) and a liquid phase
(water).

• This makes the material viscoelastic


(its mechanical properties change with
time to a constant force)
Mechanical behaviour of articular cartilage
Two types of viscoelastic behaviour
 Creep (a rapid initial deformation
followed by a slower deformation until
equilibrium)

 Stress relaxation (high initial stress on


deformation, followed by decreasing
stress until equilibrium)
Mechanical behaviour of articular cartilage

• How does this happen? It occurs because of


the water in the cartilage.

• Although both solids and water are


incompressible, when the tissue is
compressed, the water can be forced out of the
solid matrix.

• Consider a cylindrical plug of cartilage in a


container and compressed by a porous filter (A)
Under loading, fluid exudation occurs through the
porous platen in the vertical direction

1. Creep

• When compressed using the porous


filter, the water passes the filter and
collects above, whilst the solid
material below are compressed.

• Under a constant load this leads to a


rapid initial deformation, but less so
as the water leaves and the
incompressible solids remain.
2. Stress relaxation
• During deformation, the upper
layers become compressed (and
lose their water) first.

• Once the tissue is loaded to its


final capacity, the layers then
redistribute the remaining water
from the (uncompressed) bottom
to the (compressed) top.

• This continues until equilibrium is


reached, at which point the stress
reduces to a steady-state value.
The role of water
• How does the tissue get the water back?
• The PGs are very highly charged. When the water (and ions) is there, the
counter-ions “shield” these charges and keep things electrically neutral.
• When the water is squeezed out, these negative charges are no longer
screened.
• They repel each other which forces them apart, drawing the water back
in (also by electrostatics).
• This is to preserve electroneutrality, by maintaining what is known as a
Donnan equilibrium.
Tension
• Although articular cartilage in the
body is rarely subject to tensive forces,
we can still explore its behaviour to
understand the physiology behind it.

• The mechanical behavior of articular


cartilage in tension is highly complex

• When we stretch cartilage, there is an


initial non-linear (“toe”) region, then a
linear region until failure.
Tension
• The toe region occurs due to the realignment • We can observe this realignment using an
of collagen fibres along the axis of tension. electron microscope and measuring the angles
Once these are completely aligned, then the of the fibres.
behaviour will follow that of the collagen
fibres.
Dynamic Loading of Cartilage
1 Hz Faster compressive
loading results in a higher
0.1 Hz dynamic modulus
10 Hz
Stress (MPa)

40 Hz

0.01 Hz

Compressive Strain
Hysteresis

Elastic material Viscoelastic material

A viscoelastic material loses energy when a load is applied, then removed.


Hysteresis is observed in the stress–strain curve, with the area of the loop being equal to
the energy lost during the loading cycle
Behavior of Articular Cartilage in Pure Shear
If, articular cartilage is tested in pure shear under infinitesimal strain The intrinsic transient shear stress-relaxation
conditions, no pressure gradients or volumetric changes will be produced behavior of the collagen-PG solid matrix along
within the material; hence, no interstitial fluid flow will occur. with the steady dynamic shear properties

Steady dynamic shear experiment can be used to assess the viscoelastic


properties of the Collagen PG matrix (and not the fluid flow).
The magnitude of the dynamic shear modulus is a measure of the total
resistance offered by the viscoelastic material.
Permeability of Articular Cartilage
• Porosity, b, is geometric property defined as the ratio of a fluid volume to the total volume of a
material:
b=Vf/VT

• Articular cartilage is a material with high porosity (about 80%).


• Permeability is a measure of the ease with which fluid can flow through a porous material. It is inversely
proportional to frictional drag exerted by the fluid.
• The coefficient of permeability (k)is related to the frictional drag coefficient K:

k=b2/K

• Healthy cartilage has a very low permeability and thus high frictional resistive forces are generated
when the fluid flows through the porous solid matrix.
• The nonlinear permeability of cartilage suggests that the tissue has a mechanical feedback system (the
higher the loads, the stiffer the tissue and the more difficult it is to cause fluid exudation)
Permeability of Articular Cartilage
Experimental configuration used in measuring the permeability of articular cartilage, involving the application of a pressure
gradient (P1 – P2)/h across a sample of the tissue (h = tissue thickness).

Darcy’s law: describes the flow of a Permeability decreases exponentially


fluid through a porous medium as a function of both the increasing
compressive strain and and increasing
k: permeability pressure
k=Qh/A(P1-P2)
Q: volumetric flow rate
h: tissue thickness
A: cross sectional area
P: pressure
Lubrication of Articular Cartilage
• Lubrication processes limit wear of cartilage which has near frictionless
properties
• The minimal wear of normal cartilage indicates highly sophisticated
lubrication

Boundary lubrication:
• Surfaces protected by adsorbed layer of boundary lubricant
• Prevents surface to surface contact

Fluid-film lubrication:
• Uses film of lubricant causing a bearing surface (area of contact between 2
surfaces)
• Load is supported by pressure developed in fluid-film
• Two types: Squeeze Film and Hydrodynamic
Boundary Lubrication
• Surfaces protected by adsorbed layer of boundary
lubricant

• Prevents surface to surface contact

• Independent of the physical properties of the lubricant


(such as viscosity) or the bearing material (such as Low Loads, long duration
stiffness)

• Depends entirely on chemical properties of the lubricant

• In synovial joints, the main boundary lubricant is a


glycoprotein called Lubricin inside the synovial fluid

• Lubricin is adsorbed as a macromolecular monolayer to


each articulating surface.
Elasto-hydrodynamic (Fluid-Film) Lubrication

• Fluid-film utilizes a thin film of lubricant • Hydrodynamic lubrication


that causes a fluid separation. • The bearing surfaces move tangentially
with respect to each other
• The load is mainly supported by the • the load bearing capacity determined by
pressure developed in the fluid film fluid viscosity, gap geometry and sliding
speed
• The thickness required should exceed
three times the combined statistical • Squeeze film lubrication
surface roughness of cartilage. • The bearing surfaces move
perpendicularly with respect to each
other
• The two classical modes of fluid-film are • the load bearing capacity determined by
hydrodynamic and squeeze-film. fluid viscosity, size of the surfaces, and
velocity of approach

High Loads, Short duration


Lubrication of Articular Cartilage:
possible scenarios
There are two joint lubrication scenarios that can be considered a combination
of fluid-film and boundary lubrication or simply mixed lubrication

• Mixed lubrication : Combination of fluid-film and boundary lubrications:


 Temporal coexistence of both at distinct locations

Boundary lubrication occurs when the thickness of the fluid-


film is on the same order as the roughness of the bearing
surfaces. Fluid-film lubrication takes place in areas with
more widely separated surface.

During such instances, boundary lubrication between the


asperities may come into play. If this occurs, a mixed mode
of lubrication is operating
Lubrication of Articular Cartilage:
possible scenarios
• Boosted Lubrication
• In boosted lubrication, articular surfaces are protected by the
ultrafiltration of the synovial fluid through the collagen-PG matrix which
allows water and small electrolytes to pass leaving a concentrated gel of
HA protein complex that coats and lubricates the surfaces.

Boosted Lubrication is based on the


movement of fluid from the gap between
the approaching articular surfaces into the
articular cartilage
Wear of articular cartilage
• Unwanted removal of material from solid surfaces by mechanical action:

1. Interfacial wear:
• Bearing surfaces come into direct contact, with no lubricant film
separating them.

2. Fatigue wear:
• Accumulation of microscopic damage within the bearing material
under repetitive stressing

3. Wear due to synovial joint impact loading


Wear of articular cartilage (continued)
Once collagen-PG matrix is disrupted it can induce:

• Further disruption of collagen-PG matrix due to repetitive matrix


stressing

• Increased “washing out” of PGs due to violent fluid movement and


thus impairment of articular cartilage’s interstitial fluid load support
and lubrication capacity

• Gross alteration of normal load carriage mechanism in cartilage, thus


increasing frictional shear loading on the articular surface
Hypotheses on the Biomechanics of Cartilage Degeneration

• Cartilage failure progression relates to:

• Magnitude of imposed stresses


• Total number sustained stress peaks
• Changes in intrinsic molecular and microscopic structure of
collagen-PG matrix
• Changes in intrinsic mechanical property of tissue

• This is associated with decreased cartilage stiffness and increased


cartilage permeability.
ROLE OF BIOMECHANICAL FACTORS

• Articular cartilage has only a


limited capacity for repair
and regeneration, and if
subjected to an abnormal
range of stresses can quickly
undergo total failure

• Degenerative changes to the


structure and composition of
articular cartilage could lead
to abnormal tissue swelling
and functionally inferior
biomechanical properties. In
this weakened state, the
cartilage ultrastructure will
then be gradually destroyed
by stresses of normal joint
articulation
Normal vs. Eroded Cartilage
Cartilage failure
Functional Tissue Engineering of Articular Cartilage
• Cartilage has poor healing capacity.

• Role of tissue engineering :


• Incorporating an appropriate cell.
• This cell will grow fabricated tissues.
• These tissues will be used for repair and replacement of damaged or diseased
tissues and organs.
Homework:

1- Revise the topics taught in the class, and highlight the subjects that were
unclear

2- Survey those topics online, and present the list of sources that helped you
clear the subjects.

3- Answer the question:


Considering the Biomedical Engineering career, in which scenario do you
foresee the use of the subjects learned? Highlight its importance.

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