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Lecture 1 Introduction
1. Course Overview
The course will include:
2. Assessment
3.
60% examination
o Section A Short questions (no choice)
o Section B Long questions (two of three)
40% coursework
o Task will be set in late February
o Submission due mid-April (tbc)
A few basics
The scale of biological things might not be as usual as the scale of the things that are
manmade. One of the most fascinating characteristics of biology is how it organise
matter at a molecular level.
There are four organisational levels: cells, tissues, organs and systems. Cells are
important for tissue functions, mostly how tissue is created and regenerated. Cells dont
tend to provide the mechanical behaviour but they do generate and regenerate the tissue.
Cells are therefore very important for growth and healing. Tissues are cells organised
together and coordinated to provide a particular function. The cell structures formed in
the tissue are extremely complex. Each cell has a specialist job collaborating and
communicating with each other to provide a function. Organs are the organ level of the
tissues organised together. Engineers might not be able to create an organ similar to the
human organs, but they have created machines (e.g. dialysis machine) that can perform
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the same processes. The next step is to use tissue engineering to create a new organ that
has the same functions than the natural organ.
a. A generalised Eukaryotic Cell
Most of the eukaryotic cells share the structure shown in the picture above. The
nucleolus is where the DNA is stored. The DNA can be defined as the masterplan of a
human being, containing all the information required to build the human body as well as
running it. However, not every cell in the body has a nucleolus, for example the red
blood cells have not nucleolus.
The smooth endoplasmic reticulum is where the DNA information is captured, sent out
to the cell and the information is also processed. It takes the instructions included in the
DNA to actions to be performed by the cell.
A mitochondrion is an ancient bacterium. Therefore, a eukaryotic cell is a cell that has
an ancient bacteria stuck inside. The mitochondrion can be described as the cells power
plant, little energy units. They take molecules in and convert them to molecules that the
body can use as energy. The lysosome is used by the cell to eat up things and digest it.
There are two types of connective tissue in the body: tendons and ligaments.
Structurally, they are really similar. Tendons attach a muscle group onto a bone and
ligaments attach a bone onto a bone. Having said that, every single tendon and ligament
has a specific set of mechanical properties tailored to their exact position and the role
they provide. There are approximately 900 in the human body.
The largest structure in the above schematic is the tendon or the ligament itself. The
ligament or tendon then is split into smaller entities called fascicles. The fascicle
contains the basic fibril of the ligament or tendon, fibroblasts, which are the biological
cells that produce the ligament or tendon. There is a structural characteristic at this level
that plays a significant role in the mechanics of ligaments and tendons: the crimp of the
fibril. The crimp is the waviness of the fibril; we will see that this contributes
significantly to the nonlinear stress-strain relationship for ligaments and tendons and
indeed for basically all soft collagenous tissues.
Outside the ligament or tendon there is a membrane, the reticular membrane. The
membrane has two main characteristics: it helps feed the ligament or tendon from the
outside and it also helps the ligament or tendon slide. It is quite interesting that
ligaments and tendons do not have blood vessels. Therefore, ligaments and tendons
have very poor blood supply. This affects the healing properties of the ligaments and
tendons. The blood comes from the insertions, i.e. where the ligaments and tendons are
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connected to bones/muscles. This blood does not reach the middle; therefore the
nutrients are obtained from the membrane. Hence, it heals very poorly.
The fascicular membrane is located between the different fascicles (typically 3 or 4
fascicles within the ligament/tendon). The fibroblasts (within the fascicles) provide the
materials needed to create the ligament/tendon. Therefore, you rely on the fibroblasts to
generate the healing. Fibrils are used to sustain the ligament, i.e. it acts like a cable
made of several small cables.
The image on the left can be a bit confusing due to the fact that the darker and clearer
bits might look like thinner and thicker. However, this effect is due to the fact that the
ligament/tendon is desiccated before analysing it, so there no thinner and thicker parts.
Collagen is protein that makes up the majority of animal stuff. All the tissues a mammal
is made from are made from collagen. Fibroblasts manufacture short spans of collagen.
Collagen molecules find other collagen molecules forming a triple helix. This structure
is then assembled in fibril structures. It is a self-assembling process. The light and dark
parts are there because of the gaps between one and another (light) and no gaps (dark).
Although the light parts might seem structurally weak, the final structure is made to
avoid putting light parts together so distributing the strain.
The collagen is hydrophilic, i.e. it needs water. They need to suck in water. Therefore, if
you stretch it, the water comes out but you relax it, it goes back in the ligament/tendon.
The motion of water the ligament/tendon is really important as a mechanical entity. The
squeezing motion of water gives elasticity to the ligament/tendon.
There are three different types of collagen: Type I, Type II and Type III. Tendons
contain collagen Type I. It is interesting the fact that collagen is the only natural thing
with hydroxyproline in it. The main thing of the picture above is the blood supply
statements.
Blood supply is quite an important characteristic for tendons and ligaments. For
tendons, you have vessels in perimysium (membrane outside the tendon), periosteal
(steal means bone and peri means close to) insertions (where the tendon joints the bone)
and the surrounding tissues. For the ligaments, they use microvascularity from insertion
points and nutrition for cell population within the structure.
3. Connective Tissue Mechanical Properties
The figure above represents force vs. length for ligaments and tendons. It looks at the
mechanical response you get from different ligaments/tendons. Most of them have a
negligible response at the start of the action of the force. This is due to the waveform of
the collagen within the tendon/ligament. There is a reasonably elastic time and then it
reaches the top, it starts to tear up and fails. Different structures have different strengths.
The force applied to a tendon is equivalent to the force applied to the muscle. We are
overall strength not the stress-strain relationship. The Fascia lata joins a muscle group
around the hip to the side of the tibia. The Gracilis tendon goes from the ischial
tuberosity (sit bone) to the medium side of the tibia. The Gracilis tendon is often
sacrificed to be use elsewhere (usually reuse it as a ligament).
The Medial Patellar tendon joins the quadriceps to the knee cap and the Anterior
Cruciate ligament is one of the ligaments that sit in the middle of the knee.
Soft tissues are viscoelastic. Creep occurs when you apply strain and you hold it for a
certain period of time. Stress relaxation occurs when you apply stress to a
tendon/ligament and hold it and the ligament/tendon gets a bit longer with time. The
hydrophilic structure of the material is what makes it viscoelastic; therefore, the role of
water is very important with regard to mechanical properties.
4. Ageing and Soft Tissue Properties
The results shown in the
figure on the left are obtained
from New Zealand white
rabbits at 1.5, 6-7 and 40
months old. The stiffness and
strength of both ligament and
ligament-bone attachment
increased with increasing
maturity in the femur-mcltibia complex.
Collagen content and collagen
fibril diameter tend to
increase gradually in both
sexes until sexual maturation is reached. Collagen content is significantly greater in
males than in females after sexual maturation. The production of hormones oestrogen
and progesterone decreases collagen content.
As young organisms, the strength of ligaments/tendons is lower and it gets stiffer with
age.
Woo and colleagues tested FATC from young cadaver knees with an average age of 35
and older cadaver knees with an age of 76. They found that the linear structural stiffness
of the ACL decreased both when tested at 30 degrees of knee flexion and when tested
along the axis of the ligament complex. The structural stiffness in the ligament axis
averaged 183 N/mm for the younger group but only 158 N/mm for the older group.
Tests under flexion were 150 N/mm and 129 N/mm for the younger and older group
respectively. In addition, more specimens in the older group suffered avulsion failures
than the younger group.
All skeletal muscles roughly have the same structure (shown above). It can be seen that
the structure is quite similar to the hierarchical structure of soft tissue.
You have a membrane outside of the muscle, the epimysium. The purpose of the
epimysium is to allow movement of the muscle with respect to each other. The muscle
is constituted by muscle fibre (which is a single cell). When a muscle cell starts life,
cells are uni-nucleated. However, when the muscle starts growing, the cells are joined
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Depending on the purpose of the muscle, they will develop differently. For example, the
thigh muscle has to be strong whereas the spine muscle only help you maintain your
posture and therefore do not need to be that strong (fatigue-resistance muscle).
In the following figures, the contracting process is explained.
a. Attached
At the start of the cycle
shown in this figure, a
myosin head lacking a
bound nucleotide is
locked tightly onto an
actin filament in a rigor
configuration (so named
because it is responsible
for rigor mortis, the rigidity of death). In an actively contracting muscle, this state is
very short-lived, being rapidly terminated by the binding of a molecule of ATP.
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b. Released
A molecule of ATP binds
to the large cleft on the
back of the head (that
is, on the side furthest
from the actin filament)
and immediately causes a
slight change in the
conformation of the
domains that make up the
actin-binding site. This
reduces the affinity of the
head for actin and allows
it to move along the filament. The space drawn here between the head and actin
emphasises this change, although in reality the head probably remains very close to the
actin.
c. Cocked
The cleft closes like a clam shell
around the ATP molecule, triggering a
large shape change that causes the head
to be displaced along the filament by a
distance of about 5 nm. Hydrolysis of
ATP occurs, but the ADP and
inorganic phosphate (Pi) produced
remain tightly bound to the protein.
d. Force-generating
A week binding of the myosin head to a
new site on the actin filament causes
release of the inorganic phosphate
produce by ATP hydrolysis,
concomitantly with the tight binding of
the head to actin. This release triggers
the power stroke the force-generating
changing in shape during which the
head regains its original conformation.
In the course of the power stroke, the head loses its bound ADP, thereby returning to the
start of a new cycle.
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e. Attached
At the end of the cycle, the
myosin head is again locked
tightly to the actin filament in
a rigor configuration. Note that
the head has moved to a new
position on the actin filament.
Type 2A or fast oxidative-glycolytic fibres have a fast contraction speed and a high
myosin ATPase activity. They are progressively recruited when additional effort is
required, but are still very resistant to fatigue. Their motor neurones show bursts of
intermittent activity. These cells are thin (high surface to volume ratio) with a good
capillary supply for efficient gas exchange. They are rich in mitochondria and
myoglobin which gives them a red colour. They are built for aerobic metabolism and
can cause either glucose or fats as a source of energy. These are general purpose muscle
fibres which give the edge in athletic performance, but they are more expensive to
operate than type 1.
Type 2B or fast glycolytic fibres have a fast contraction speed and high myosin ATPase
activity. They are only recruited for brief maximal efforts and are easily fatigued. Their
motor neurones transmit occasional bursts of very high frequency impulses. These are
large cells with a poor surface to volume ratio and their limited capillary supply slows
the delivery of oxygen and removal of waste products. They have few mitochondria and
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little myoglobin, resulting in a white colour (e.g. chicken breast). They generate ATP by
the anaerobic fermentation of glucose to lactic acid. These are sprinters muscle fibres,
no use for sustained performance.
5. Contractile Properties of Muscle
a. Isometric Force-Length Relationship
The Force-Length relationship, also called the Length-Tension curve is shown in the
Figure below.
IM represents the optimal muscle fibre length. Isometric represent constant muscle
length and isokinetic is the constant rate of change of muscle length.
Muscles operate with greatest active force when close to an ideal length (often their
resting length). When stretched or shortened beyond this (whether due to the action of
the muscle itself or by an outside force), the maximum active force generated decreases.
This decrease is minimal for small deviations, but the force drops off rapidly as the
length deviates further from the ideal. As a result, in most biological systems, the range
of muscle contraction will remain on the peak of the length-tension curve, in order to
maximise contraction force. Due to the presence of elastic proteins within a muscle, as
the muscle is stretched beyond a given length, there is an entirely passive force which
opposed lengthening. Combined together, we see a strong resistance to lengthening an
active muscle far beyond the peak of active force.
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b. Force-Velocity Relationship
The Force-Velocity relationship is the rate at which a muscle is stretched or shortened.
External forces, such as load or other muscles, usually regulate this; hence, it also
affects the force it can generate. Concentric defines when the muscle shortens as it
contracts and eccentric is when the muscle lengthens as it contracts.
As the shortening velocity increases, the force it can generate compared to when
isometric decreases in a hyperbolic fashion, eventually reaching zero at some maximum
velocity. However, the reverse holds true for when the muscle is stretched force
increases above isometric maximum, until finally reaching an absolute maximum. This
has strong implications for the rate at which muscles can perform mechanical work
(power). Since power is equal to force times velocity, the muscle generates no power at
either isometric force (due to zero velocity) or maximal velocity (due to zero force).
Instead, the optimal shortening velocity for power generation is approximately one-third
of maximum shortening velocity.
6. Tetanus
The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the
Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani. Infection
generally occurs through wound contamination and often involves a cut or deep
puncture wound. As the infection progresses, muscle spasms develop in the jaw and
elsewhere in the body.
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2. Engineering Materials
a. Linear Elasticity
Hookes Law defines linear elasticity, which is an
appropriate assumption for many materials. Many
engineering materials can be assumed to be Hookean
for small strains. In reality, all materials are nonHookean.
b. Linear Viscous Fluids
Fluids behave in a similar way,
differentiating between Newtonian fluids
and non-Newtonian fluids.
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3. Viscoelasticity
Three characteristic behaviours are observed, as shown in the figures below.
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It this case, you have a simple model of a spring in parallel with a dashpot. This can be
defined as follows:
= ! + ! (1)
= ! = ! (2) and therefore = ! = !
We also know that:
! = ! ! ! = ! !
where E is the Young Modulus. Using (1):
= ! + ! = ! ! + ! ! (3)
Combining (2) and (3):
! = ! + !
b. Maxwell Fluid Model
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!
+
Hence,
= ! = ! =
!
!
+
+
!
as = ! = ! ,
=
+
+
!
Multiplying through by + ,
+ = +
+ =
+ 1 +
!
!
!
+ =
+ !
+
!
!
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!
!
cos !! = sin
!
!
The loss angle d, or the loss tangent tan d, may be considered as the fundamental
measure of damping in a linear material. Other measures, such as those developed
before, are often cited in analyses of viscoelastic behaviour.
5. Non-Linear Viscosity
The relaxation modulus G(t) varies
with the initial stress. Also, it can be
observed that the error bars are large,
which implies that there is an
inherent problem with empirical
work on biological systems.
The experiment shows an isochronal
curve at time 2.4s obtained from
stress relaxation tests performed on
15 Rabbit Medial Collaterals (MCL).
The graph shows the non-linear strain-stiffening behaviour found in ligaments. The
error bars represent the standard deviation.
The rates of creep and relaxation vary, as shown in the figures below.
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The figure on the left shows stress vs. rate of creep relaxation. The rate of creep is seen
to be non-linear with respect to stress. This figure represents the data pooled together
from both testing protocols (multiple stress level and repeated stress level) for creep
tests. The graph shows that the rate of creep (n) changes by an order of magnitude
through the low load region.
The figure on the right shows strain vs. rate of stress relaxation. The rate of stress
relaxation is seen to be non-linear with respect to strain. The figure represents the data
pooled together from both testing protocols (multiple strain level and repeated strain
level) for stress relaxation tests. The graph shows that the rate of relaxation (n) changes
by an order of magnitude throughout the low load region.
Additionally, the rate of creep decreases
when the stress level is increased, as can
be see in the figure on the left. Indeed, the
graph shows creep at multiple levels of
stress (Log-Log scale).
In case the strain varies smoothly with time the superposition of the effects of the
!!
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Note that this means that the elementary increment of strain at the previous time
leads to an elementary increment of stress at the current time t given by:
= ( )()
The integration starting at = means that the effects of all relevant previous strain
changes must be taken into account.
Assuming that the deformation starts at =0, with (=0) for <0, and that possibly nonvanishing jump exist at = 0 0 0 = 0 , it follows from (S) and (I) that:
All the above developments show that in linear viscoelasticity the stresses depend
linearly on the strains and the stress at the current time t results from the linear
superposition of the effects of the strain changes in all relevant previous times .
b. Fungs Quasilinear Theory for bio-viscoelastic solids (1D)
Fungs theory is also based on the idea of linearly superposing at the current time the
effects from past changes in the system, and leads also to a hereditary integral. But the
theory cannot preserve the linear dependence of the stresses on the strains, since, as
already observed, the elastic behaviour of the soft tissues typically is highly non-linear.
Let T be the nominal stress, the stretch ratio, and let T(e)() denote the instantaneous
elastic response of the material, i.e. the stress instantaneously generated in the tissue
when a step stretch ratio is imposed on the tissue. In other words, T(e)() characterises
the elastic constitutive law that holds when relaxation effects are not taken into account.
T(e)() is typically a non-linear function that frequently involves exponential
contributions.
In the figure below, (t)=1, T(e)(t)=0, for t<0. At t=0, a step stretch ratio is imposed on
the tissue such that, for all t>0, (t)=(0*) and by definition of T(e)
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Comparing these results with the linear viscoelasticity, it should be clear that:
Assuming that ()=1, T(e)( )=0 for <0, the proposed 1D quasilinear constitutive
equation for soft tissues has the form:
Consequently, this constitutive law involves linear superposition of the effects of the
instantaneous elastic stresses at all previous times. Linear viscoelasticity involves linear
superposition of strains, which is not valid in quasilinear viscoelasticity.
It is important to consider the fact that the rate of stress decreases as creep increases, as
shown in the figure below. The QLV model fails to fit experimental data at higher
initial strain levels.
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Postoperatively, the arm was placed in a full-length splint. Perfusion to the free flap was
monitored for one week using continuous Laser Doppler Flow (LDF) readings. The
hand and elbow were immobilised for four weeks at which time sutures and the
proximal radio-ulnar pin was removed. The wrist remained splinted but active ROM
was begun at the MCP, PIP and DIP joints of the figures and at the elbow.
At the six week mar, the pin across the MP joint of the thumb was removed, and a
removable thermoplastic splint was applied. Aggressive physiotherapy of the elbow
(flexion / extension / pronation / supination) was begun, as was active and passive ROM
of the fingers. Two months postoperatively, the patient was doing well, had regained 15 to 90 degrees of flexion at the MCP joints of her fingers, full ROM of the PIP/DIP
joints, and could pro/supinate 60 degrees each direction. The free flap remained viable
and this young woman is scheduled for debulking of the free flap approximately six
months from her last surgery.
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The mid-section, called diaphysis, is made of cortical bone. The end-sections, i.e.
metaphysis and epiphysis, are made of cancellous bone. The physis, or growth plate,
are the start from where the bone grows.
Why do we have cancellous bone at the end and compact bone in the middle? Bending
moments are higher in the mid-section so a nice, thick tubular structure is more
appropriate (tube greater bending stiffness, 2nd moment). Also, cancellous bone is
found at the end of the bone, where bones are connected to the joints, which is a large
surface area used to transfer loads. Besides, if it were compact bone, the shell would
collapse under the loads.
Lamellar bone may be formed as a solid mass in compact (cortical) bone or as an
open, sponge-like network in cancellous (trabecular or spongy) bone. Most bones are
organised such that they have a rigid, outer cortical shell of compact bone and an inner
cancellous zone, the strength of which is provided by its connecting meshwork of
trabeculae. The spaces between trabeculae and the central medullary cavity are filled
with bone marrow where haematopoiesis (blood cell formation) occurs (red bone
marrow) or adipocytes are found (yellow bone marrow).
Lining Haversian canals and internal surfaces of the marrow cavities is the endosteum, a
layer of stem cells and inactive osteoblasts. A fibrocollagenous connective tissue layer,
the periosteum surrounds most outer surfaces of bone and contains numerous stem cells
and the neurovascular supply of the bone.
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c. At a Molecular Level
At a molecular level, we observe collagen and
Hydroxyapatite (Ca5(PO4)3(OH)). Collagen for bone has
become mineralised, i.e. it has embedded crystals of
calcium.
A natural composite material, protein + ceramic (matrix of
collagen) makes up the compact bone.
2. Hierarchical Bone Structure
There are two paths: (A) come from tissue stem cells and (B) come from blood stem
cells. Osteoblast, osteocyte (A) and osteoclast (B) differentiation is shown in the figure
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above. Preosteoblasts start to differentiate slowly from mesenchymal stem cell in the
bone marrow until they have the location and phenotype of osteoblasts. As the osteoid
becomes mineralised by osteoblasts, these cells become enclosed in lacuna as
osteocytes. Osteoclasts are giant multinucleate cells that differentiate from
hematopoietic cells of the monocytes/macrophage lineage in the bone marrow.
4. Mechanical Properties of Bone 1
a. Healthy Cortical
The figure on the left shows the typical stress-strain behaviour for human cortical bone.
The bone is stiffer in the longitudinal direction, indicative of its elastic anisotropy. It is
also stronger in compression than tension, indicative of its strength asymmetry
(modulus is the same in tension and compression).
The figure on the right shows the creep response of cortical bone for three different
stress levels. When a low stress is applied to the bone, the strain remains constant over
time, and there is no permanent deformation after unloading. For stress just below yield,
strains increase with time at a constant rate, and a small permanent deformation exists
after unloading. As the magnitude of the stress is increased, the rate of creep increases,
and a larger permanent deformation exists after unloading.
For bone, we know that it is stronger on compression than on tension.
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Several points can be extracted from the figures above (dependence of UTS of human
cortical bone on volume fraction in % (ages ranged 20-100) on the left and the modulus
versus calcium content in 18 different species on the right:
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b. Healthy Trabecular
It can be observed in the figure on
the left that the trabecular bone of
the femur is much stronger than the
trabecular bone found in the
vertebra.
For both of these, it is interesting to
see how it becomes weaker with
age, in a linear sort of way.
The figure above shows the dependence of yield stress in tension, compression and
torsion on apparent density for bovine tibial trabecular bone specimens oriented
longitudinally and transverse to the principal trabecular orientation. Overall, strength is
greatest in compression and least in shear. In compression, the strength-anisotropy ratio
[SAR = (longitudinal strength)/(transverse strength)] increases with decreasing density.
5. Bone Fatigue
The figure on the left shows fatigue and creep
behaviours for human cortical bone versus
time to failure. For fatigue loading, the
ordinate on this graph can be converted to
cycles by multiplying the time to failure by the
frequency, which is typically one cycle per
second for normal walking. Note that creep
and fatigue resistance are lower in tension,
consistent with the monotonic behaviour.
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IF you are rigorous exerciser, there is a point where you will be exposed to fatigue
damage, really quite quickly.
The figure on the left shows the comparison of loading and reloading tensile stressstrain curves for human cortical bone. On reloading, the modulus is similar to that for
initial loading but it is quickly reduced to a value that is close to the perfect damage
modulus, the secant modulus at the unloading point. Substantial residual strains are
evident after 1 and 2 minute holds between cycles. Nf represents cycles to failure and
delta epsilon is the applied strain amplitude.
The figure on the right shows the compressive load-unload-load behaviour of human
vertebral trabecular/cancellous bone. Similar to cortical bone tested in tension, an initial
overload causes residual strains and a reloading curve whose modulus quickly reduces
from a value similar to the intact modulus to a value similar to the perfect damage
modulus.
As a general note, generic difficulty with in vitro fatigue measurements that bodys
healing processes are not occurring over the timeline. These experiments have to be
assumed to be worst-case scenarios.
6. Bone Fracture Mechanics
The figure shows the variation of
cortical bone fracture toughness Kc,
with bone density for longitudinal
slow crack growth. Solid circles are
bovine femoral data at 0.06 cm/min
and open circles are 0.003 cm/min.
Fracture toughness Kc is the
measurement of the resistance of a
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The toughness of the bone can be increased by making it difficult for the crack to grow.
Presumably, there are many mechanisms involved in this process in bone, two of which
are illustrated above unbroken collagen fibrils bridge the crack and damage ahead of
the notch at a Haversian canal consumes energy and may cause the crack from the
growing tip to deflect.
Stress fracture by micro-cracking:
9. Bone Remodelling
The figure on the left
represents Wolffs
Law.
This law holds that
every change in the
form or function of a
bone is followed by
adaptive changes in its
internal architecture
and its external shape.
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38
Closed or simple fracture the bone is broken, but the skin is not lacerated
Open or compound fracture the skin may be pierced by the bone or by a blow
that breaks the skin at the time of the fracture. The bone many or may not be
visible in the wound
Transverse fracture the fracture is at right angles to the long axis of the bone
Greenstick fracture fracture on one side of the bone, causing a bend on the
other side of the bone. This is common in children due to the fact that their
bones are more flexible (less mineralised)
Comminuted fracture a fracture that results in three or more bone fragments,
which is interesting in terms of how to manage the healing process
Spiral fracture fracture due to torsion
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2. Bone Healing
Primary versus secondary mineralised tissue repair. (A) When a small fracture gap
occurs and bone remains stabilised, osteoblasts deposit bone perpendicular t the bones
long axis, filling the gap and serving as a scaffold for future remodelling. (B) In primary
contact repair, fractured ends are held in direct apposition. No excess ECM is required.
Cutting cones are formed as osteoblasts absorb damaged bone, followed by osteoblasts
synthesising osteoid, which becomes mineralised to form lamellar bone. (C)
Unstabilised fractures are initially repaired through ECM production by fibroblasts and
chondrocytes arriving from the periosteum to form a stabilising soft callus. The
collagenous ECM becomes mineralised, forming woven bone, also referred to as hard
callus.
In conclusion, bone healing is not necessarily just one process.
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around and get release home Over the next two years, hard callus will be
gradually replaced: woven bone replaced by cortical via the osteons
moving around. The ballooning would be completely replaced under
perfect healing circumstances and become as it used to be; this is
unlikely in practice, so the callus will remain there for many, many
years. Obviously this depends on age, but such breaks are unlikely to be
encountered in young people.
a. Pagets Disease
Pagets disease of bone is a condition in which the normal cycle of bone growth is
disrupted. This can cause bones to become weakened and deformed.
After osteoporosis (brittle bones), Pagets disease is the second most common type of
bone disease.
For reasons that are unclear, Pagets disease is most common amongst people of British
descent. The condition is most widespread in the UK, and is relatively widespread in
countries that have experienced high levels of migration from the UK, such as the US,
Australia, New Zealand and South Africa.
Pagets disease is an age-related condition. It is estimated that 1-2% of white adults who
are over 55 years of age have Pagets disease. This figure rises to 5-8% for white people
who are over 80 years of age.
The causes of Pagets disease are unknown, but it has been suggested that it could be
triggered by a combination of environmental and genetic factors.
3. Mechanobiology of Bone Healing
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The bone wants to get back to the lamella bone stage. As part of the process, we will
create woven bone. But there are different types of it and different routes to it.
If the body gets strain across the fraction (motion at the wound site) while healing, it
directs towards fibrous cells, laying down the random collagen spaghetti. If you do not
have motion (no strain) but you have hydrostatic pressure in the wound, you get tissue
more skin to cartilage laid down. Over time, it will be re-mineralised into lamella bone.
measureable indents due to extremely high compliance of the tissue at those indent
locations. (B) Approximately matched CT cross-section to (A). Indentation modulus
and TMD for each of the five VOIs are also defined.
For indentation modulus, the height of each bar and of each error bar represents the
mean and standard deviation, respectively, of all indents in the VOI for both calluses
(e.g. n = 176 for the centre of the gap). In contrast, each callus yields only one value of
TMD for each VOI. Hence, for TMD, the height of each bar and of each error bar
represent the mean and standard deviation, respectively, of the average TMD values of
the two calluses (n = 2 for each VOI). Bars that are not labelled with the same number
(indentation modulus) or letter (TMD) are significantly different from one another
(P<0.05).
b. Time of Healing
The mechanical properties of the bone that will be stabilised are changing with time.
Therefore, in the best case, our stabilising material would change its properties too. The
main characteristics are:
b. External Fixator
This device was invented by Lizarov in Russia and then
used in western countries. Until recently, it was only used
for severe trauma involving soft tissue damage.
Improvements in bone screw design and insertion
techniques allied to easier mechanics of frame assembly
have widened its appeal.
There is nothing going happening on the inside. Pins are
located into the bone, which provides external support.
This technique is interesting because you really tune the
stiffness to the particular time point. As fracture heals,
you can reduce the amount of metalwork, reducing the
stiffness of the fixator as the stiffness of the callus starts
to increase.
The design gives freedom to make adjustments over time to correct skeletal deformity
and leg lengthening. Note the use of multiplanar pin insertion and circular frames.
Because you can use the external to drive the deformity, it is good for deformity
healing.
As the callus mineralisation increases so does the stiffness.
When the load taken by callus is increasing, two things must
be done:
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For cortical bone, a very shallow, less open, self-tapping screw thread is used. This is
due to the fact that this screw is less likely to pull out.
The canulated has a characteristic hole in the middle. You are often not able to maintain
a good field of view in the wound (blood, etc.); hence, using these screws you can use a
guide wire to help you control the wound. This kind of screws would probably stay in
the body for good.
Many designs and sizes of bone plates
are used for myriad fracture types and
locations.
This is particularly used in fractures of
the arm as well as the face (e.g. jaw),
you would not tend to see them used in legs simply because they are not strong enough.
There are two different types, with a difference in how the head of the screw interacts
with the top of the bone plate.
a. Conventional plates Non-locking screws
In conventional plate fixation, as the
screws are tightened, and the screws
displace the bone into compression, a
compressive force is generated between the
plate and the bone. This compressive force
must be sufficient in order to generate
46
enough friction between the plate and the bone to maintain stability of the fracture. As
long as the resultant load from body weight and muscles do not exceed what the
frictional interface can support, the construct will remain stable and prevent collapse.
As you screw down, the bone is pushed to the side () due to the way the screw head is
made. This helps get the two bones closer together, promoting direct contact type of
healing. It will not be proper contact repair because the periosteum is broken. However,
no fracture is of a certain perfect type, but a mixture of the types of healing.
The big concern with this type of healing process is the fact that you have created a
huge contact stress between the bone and the plate, seriously squashing the periosteum
as well as compromising blood supply and possibly damaging the periosteum.
We must also take into consideration Wolffs Law, i.e. bone responds to its mechanical
environment. In this case, the stiff piece of metal is taking a lot of the load, so it is
possible that the bone will decide it is not need and in the long term this could lead to
resorption, i.e. a weakened bone. This is why you would usually want to take it out after
a time.
Taking a plate in/out is a very invasive operation since you need to get through nerves,
which might lead to significant risk of damage (e.g. in the arm it could be the muscles).
Therefore, plates are now reserved for special cases.
b. Locking Plates
The figure above shows the initial stress in the bone due to tightening (roughly 0).
When the bone is loaded along the axes of the bone, the bone around the screw is
compressed on the load side of the fracture.
The main difference with conventional plates is the fact that the screws have heads wit
thread in them. This system eliminates the contact between plate and bone, preserving
the periosteum and bone supply. There is also less chance for stress shielding (which
causes bone resorption). You are not trying to put the bones together.
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c. Comparison of plates
The figure above shows the initial stress in the bone due to tightening. When the bone is
loaded along the axes of the bone, the bone around the screw is compressed on the load
side of the fracture.
As the load is increased, and the angle between the screw and the plate starts to change,
the resultant loading vector on the screw changes from pure compression to a
compressive and a tensile component. It is this additional tensile component which,
when the elastic limit of the bone is exceeded, will cause toggling and eventual collapse
across the fracture gap. On the other side, the bottom figure shows no load transfer, i.e.
a much more efficient system.
For the figure on the top, the cortical bone has a grain to it due to the osteons, so the
screws will find it easier to move along those grains. Also creep will help with the
screws moving. This reason why is not currently used in leg is because the leg is
exposed to frequent, high and continuous loads.
Regarding the plate, hardly any strain will be found on the plate side whereas more
strain will be observable on the non-plate side. This will create a bending moment. A
complex strain environment is created, which is not great for the healing process since
an ideal, controlled strain environment is preferred.
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d. Unstable Constructs
A construct in which compression cannot be achieved across the fracture is unstable and
at risk for failure. Plates alone cannot tolerate the functional loads of a limb, and if the
fracture does not heal, the construct may eventually fail due to fatigue under cyclical
loading.
This situation may be due to:
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e. Nails
Factors that affect the rigidity of intramedullary nailing include the cross section of the
rod, whether distal screws are used (especially to increase torsional rigidity), and the
material from which the rod is made. Although in general less stiff than either plate or
external fixation, the advantage of intramedullary nailing for femoral shaft is early
ambulation, ease of surgery, and the ability to remove rod relatively easily.
There are two types of nails:
Reamed (left)
o Early designs
o Out of favour
Unreamed (right)
o Various configurations of locking screws
Unreamed nails are pushed into the canal of the bone. Then,
the nails are screwed into place at either end.
Reamed nails require removing the canal to then put the
nail in.
Screwing the nail in will make it much stiffer at either end. The reamed one relies on the
friction between the nail and the bone to transfer the load whereas the unreamed ones
transfer the load using the screws.
This technique is good for fractures in the area of the diaphysis. Also, because the nail
is in the middle of the bone, this method provides very good strain environment for the
healing, but there is a possibility of stress shielding if you leave the nail; therefore, you
will want to take it out as soon as possible.
The figure bellow shows different nail cross sections:
The Kntscher one is based on the use of reaming and undersized slotted nail that
results in compression of nail and a force exerted on the IM canal and interference fit.
Early ones were solid. Then, they decided these were to stiff so they made them hollow.
However, they later realised they were not stiff enough and so on. They were optimised
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over time, being the Russel-Taylor the most common at that stage. However, the most
common is the AIM, which strives for isoelasticity.
Different results of nail bending stiffness are shown in the figure below.
Slots are introduced since they make things less thick from the torsions point of view.
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Fibrous
o Gomphosis it is a joint that binds the teeth to bony sockets (dental
alveoli) in the maxillary bone and mandible.
o Syndesmosis it is a slightly movable articulation where the contiguous
bony surfaces are united by an interesseous ligament. For example,
tibiofubular syndesmosis is formed by the rough, convex surface of the
medial side of the lower end of the fibula, and a rough concave surface
on the lateral side of the tibia.
o Suture a type of fibrous joint, which only occurs in the skull (or
cranium). They are bound together by Sharpeys fibres.
o Interosseous membrane it is a broad and thin plane of fibrous tissue
that separates many of the bones of the body, e.g. in the forearm and
shank.
Cartilaginous
o Synchondrosis it is where the connecting medium is hyaline cartilage.
For example, you can find it as the sternocostal joints.
o Symphysis it is a fibrocartilaginous fusion between two bones. It is a
type of cartilaginous joint, specifically a secondary cartilaginous joint. A
symphysis is an amphiarthrosis, a slightly movable joint. For example,
the pubic symphysis and the intervertebral disc.
Synovial
Synovial
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In the figure:
Fibrous
o (A) syndesmosis (tibiofibular);
o (B) suture (skull)
Cartilaginous
o (C) symphysis (vertebral bodies);
o (D) synchondrosis (first rib and sternum);
Synovial
o (E) condyloid (wrist)
o (F) gliding (radioanular)
o (G) hinge or ginglymus (elbow)
o (H) ball and socket (hip)
o (I) saddle (carpometacarpal of thumb)
o (J) pivot (atlantoaxial)
2. Synovial Joints
There are several different types of synovial joints, as it can be observed in the figure
below.
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The superficial or tangential zone contains the highest collagen content, about 85% by
dry weight. In addition, the collagen fibrils are oriented parallel to the joint surface,
54
indicating that the purpose of this may be primarily to resist shear stress. The amount of
collagen decreases in each zone moving closer to the tidemark, dropping to 68% in the
middle zone.
Cartilage is slivery due to the fact there is no blood supply. It also des not have any
nerve cells because you would not want it to feel pain.
The bone at the bottom of the first picture is impervious (from the tidemark) so nutrients
cannot pass. The top right figure shows the collagen fibre orientation, which, as can be
seen, changes with how close it is to the bone.
Cartilage is not stiff, as it has no mineral crystals like bones do. The collagen only has
strength in tension, where as it is basically always in compression. Cartilage collagen
fibres form hoops, which are in tension because the water absorbing molecules inflate
the space like a balloon. So this explains how the fibres in tension transferred
compression.
Chondrocytes manufacture the collagen constantly. All their nutrients come through the
synovial fluid since there is no blood supply. The synovial joint is also where the water
comes from. Additionally, the top surface has all these molecules that act as lubricant.
The figures at the bottom show the relation between water molecules (proteoglycans)
and the collagen molecules. This is another example of how hierarchical structures lead
to the different abilities and functions.
a. Composition
The composition of the articular cartilage is shown in the table and figure below.
determined by the swelling pressure due to the fixed charge density (FCD) of the
proteoglycans. In other words, the proteoglycans have strong negative electric charges.
The proteoglycans are constrained within the collagen matrix. Because the
proteoglycans are bound closely, the closeness of the negative charges creates a
repulsion for that must be neutralised by positive ions in the surrounding fluid. The
higher concentration of ions in the tissue compared to outside the tissue leads to
swelling pressures. The exclusion of water raises the density of fixed charge, which in
turn raises the swelling pressure and charge-charge repulsion. The amount of water
present in turn raises the swelling pressure and charge-charge repulsion. The amount of
water present in cartilage depends on (1) the concentration of proteoglycans, which
determines FCD and swelling pressure, (2) the organisation of the collagen network,
and (3) the stiffness and strength of the collagen network. The collagen network resists
the swelling of the articular cartilage. If the collagen network is degraded, as in the case
of OA, the amount of water in the cartilage increases, because more negative ions are
exposed to draw in fluid. The increase in fluid can significantly alter the mechanical
behaviour of the cartilage.
The third major components of cartilage are the proteoglycans. Proteoglycans are large
biomolecules that consist of a protein core with glycosaminoglycan side chains. These
molecules normally occupy much larger space when compacted by a collagen network.
The compaction of the proteoglycans affects swelling pressure as well as fluid motion
under compression. This also allows for better holding of the water particles.
b. Mechanical Properties
As perhaps can be gleaned from the previous sections, there are three major factors that
contribute to articular cartilage mechanical behaviour. First, there is the swelling
pressure due to the ionic affects in the tissue. Second, there is the elastic behaviour of
the solid matrix itself. Third, there is the fluid-solid interaction in the cartilage under
compressive load.
As you squeeze the cartilage, the water can only go sideways. This creates the fluidsolid interaction, i.e. the viscosity of the fluid and the fluid interacting with the solid
matrix.
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This theory (figure above) captures the basic behaviour of cartilage under compression.
As an example, the behaviour of cartilage under compression is shown above.
In this case, cartilage is subjected to a fixed displaced at point (B). Because the fluid
cannot immediately leave, it carries a good portion of the load. As the fluid leaves the
cartilage, load is shifted to the solid matrix and stress is reduced. The spike at (B) in the
graph is due to the fact that a finite amount of time is needed for the fluid to move
initially.
Two key material properties in biphasic theory are equilibrium modulus and
permeability. Equilibrium modulus is the stiffness of the cartilage as all the fluid flows
out.
5. Synovial Fluid
Synovial fluid is produced by the synovial membrane. The main outcome is to dialysate
(ultrafiltrate) the blood. No cells are found and it is stripped of high Mw proteins.
The protein encoded by this gene is a large proteoglycan specifically synthesised by
chondrocytes located at the surface of articular cartilage, and also by synovial lining
cells. This protein contains both chondroitin sulphate and keratin sulphate
glycosaminoglycan. It functions as a boundary lubricant at the cartilage surface and
contributes to the elastic absorption and energy dissipation of synovial fluid.
The synovium adds particular biomolecules to the synovial fluid, i.e.:
o Viscosity modifier
Lubricin
o A.k.a. PRG4
A controversy is whether the lubricin actually exists, since it is considered more like a
cluster of different molecules coming together to form these lubricant ball bearings at a
Nano scale.
a. Viscosity
The synovial fluid is a non-Newtonian fluid, i.e. has pseudo-plastic, shear thinning
properties. It is however not known how the biomolecular components achieve this.
The figure on the left shows the shearrate-dependent-viscosity of the CACPhSF, BSF (normal synovial fluid), ETBSF, UHA and UHA with added
lubricin measured in the rheometer.
After the addition of lubricin, the zeroshear viscosity of UHA decreased
considerably. An increase in zero-shear
viscosity was also noted in BSF after
digestion with trypsin. The onset of
power-law behaviour (between arrows)
at greater shear rates in the CACP-hSF
sample may be attributable to a wider range in the molecular weight distribution of HA.
Captodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is cased by
truncating mutations in the gene PRG4, leading to no lubricin expression.
In conclusion, the graph shows that:
6. Lubrication
Considering a day in your day, you could observe a vast range of tribological
conditions. You stand around or lie around amounts of time and then within an instant
when you start to move you want perfectly frictionless, perfectly mobile joints. You
also want to keep the same friction over, for example, the entire 4 hours of running a
marathon.
There are several types of lubrication. However, nature achieves a better type of
lubrication by combining all lubricants simultaneously.
Hydrodynamic
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Squeeze film
Boosted
Weeping
Boundary
a. Hydrodynamic
You do not want to have
the two sides touching
each other. Lubricant is
entrained in the front end.
This results in fluid
pressurisation and load
support.
b. Squeeze Film
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d. Boundary
This method allows the surface of the cartilage to hold to water better. The body can use
different modes or combinations of lubrication.
7. Diseases Osteoarthritis
This disease is attributed to wear &
tear. It is a traumatic event related to
obesity. Indeed, 8.5 million Britons are
affected.
In this disease, cartilage becomes
thinner. It also loses strength as well as
increases the amount of calcification.
The pain comes late in the process
when cartilage is severely degraded.
Regarding the synovial fluid, the
viscosity is reduced but the volume is
increased.
The reduction of tensile strength is shown in the table below.
The concept of fibrillation is
the initial degenerative
changes in osteoarthritis,
marked by softening of the
articular cartilage and the
development of vertical clefts
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Analgesics
Non-steroidal anti-inflammatory drugs (NSAIDs)
Disease-modifying anti-rheumatic drugs (DMARDs)
Corticosteroids
61
The elbow and ankle are the next most common joints affected. In the elbow, it affects
the capitellum of the humerus and, in the ankle, it affects the talar dome.
In conclusion, 5% of OA suffered have had OD.
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The hip joint is supplied with blood from the medial circumflex femoral and lateral
circumflex femoral arteries, which are both usually branches of the deep artery of the
thigh (profunda femoris), but there are numerous variations and one or both may also
arise directly from the femoral artery. There is also a small contribution from a small
artery in the ligament of the head of the femur, which is a branch of the posterior
division of the obturator artery, which becomes important to avoid avascular necrosis of
the head of the femur when the blood supply from the medial and lateral circumflex are
disrupted (e.g. through fracture of the neck of the femur along their course).
The hip has two anatomically important anastomoses, the cruciate and the trochanteric
anastomoses, the latter of which provides most of the blood to the head of the femur.
These anastomoses exist between the femoral artery or profunda femoris and the gluteal
vessels.
a. Huge Range of Motion
Lateral or external rotation
(30 degrees with the hip extended, 50
degrees with the hip flexed)
Medial or internal rotation
(40 degrees)
Extension or retroversion (20
degrees)
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Avascular necrosis is a disease resulting from the temporary or permanent loss of the
blood supply to an area of bone. Without blood, the bone tissue dies and the bone
collapses. If avascular necrosis involves the bones of a joint, it often leads to destruction
of the joint articular surfaces, or Osteochondritis dissecans.
c. Congenital (or developmental) Dysplasia of the Hip
The cause for this is unknown. However, there are several risk factors:
This case occurs in about 1 out of 1,000 births. Several treatments for CDH are
available, depending on when it is caught:
Methods for reconstructing the hip have been changed and improved over the years:
3. Hemiarthroplasty
Different options are available:
High-density polyethylene is the most common polymer for total hip arthroplasty.
4. Total Hip Arthroplasty
It is important to consider how the cup is located in the pelvis; indeed, it is meant to be
about 45 degrees and neutral (not open or closed orientation). They are often put in too
vertically leading to it being much easier to dislocate. If it is to open, no many problems
65
are encountered. On the other hand, if placed to closed-oriented (i.e. hole facing the
back), the neck of the other part of the replacement will hit the rim of the cup, easily
leading to dislocation. Additionally, it is really not possible to fix misplaced joints.
Philip Wiles worked out a replacement based on stainless steel against itself, with screw
and bolt fixation. The weight of the replacement does not matter (100 g does not make a
difference for the full body weight).
Bone cement was developed by Haboush in the 1940/50s. Joint replacements are held in
place by bone cement or interference fit with spaces in metal to which the bone can
grow into. The process starts with the replacement being hammered inside a bit, and
then stopping to let the bone creep, then hammering it again achieving initial
interference fit.
There was a general concern called cement disease due to the fact that an
inflammation was detected and was thought to be caused by cement particles.
Mc-Kee-Farrar introduced the metal on metal design and Charnley introduced the metal
on polymer one, as it can be observed in the figures below.
McMinn introduce the resurfacing method (BHR) with a metal-on-metal. This process
was the result of efforts to minimize amount of bone being taken out. This involves:
Do not cut femoral head. Instead, reshape it. The pin fits in the head but it does
not go all the way down.
The cup is metal because the cup is too thin to use plastic.
5. Ostelolysis
Osteolyis, also called aseptic loosening is a lesion that is considered
the principal cause of long-term failure for the hip replacement. This
happens to 10% of THR at 10 years time. This disease was first seen in
the 60s but not really recognised. This is observable in the figure on the
left.
66
67
macrophages die once its too full (it cant digest plastic compared to bacteria),
releasing all those wear particles all over again.
Cytokine release represents the signal that is sent to other macrophages to come in. The
severity of response depends on:
Material
Number of particles
Size/volume of particles
Morphology of particles
b. Hypothesis 2
Per Aspenberg suggested a cyclical hydraulic erosion of the
joint due to use. The osteolytic cavity created due to the
hydraulic pressure. The debris gets in by accident.
It was found that bigger debris stays near the joint whereas
small debris travels far away, even to your brains.
Macrophages cannot wrap around things over 5 microns,
but they can join to form bigger cells to deal with these.
Only at sizes of ~millimetres are ignored by the body
system.
6. THR Wear
The data gathered is from ultra high molecular weight PE data, but it is not really used
anymore.
68
69
In this equation, is the coefficient of friction. For dry contacts, this coefficient is 0.10.4. For lubricated contacts, 0.001-0.1.
Friction is independent of the contact
area between two surfaces. The
reason that force is the same in either
case is due to the differences
between the apparent area of contact
and the actual area of contact.
Surfaces are generally wavy and
bumpy, even at microscopic level.
Therefore, two adjacent surfaces, as
shown in the figure on the left, are
never in total contact. The upper
body is supported by the lower body surface at the top of roughness irregularities, called
asperities. Under load, these asperities bend and deform until the load is fully supported.
At that point, less than 1 part in 10,000 of the apparent area is usually in contact.
Friction is indirectly proportional to the real area of contact. Since this is almost always
a small portion of the total area, friction is effectively independent of the apparent area
of contact.
2. Coulombs Law
Coulombs Law states that friction is independent of velocity. Both Amontons and
Coulombs laws only apply to dry contacts.
3. Tribological Contacts
It is mandatory to explain the difference between friction and wear, since these terms
are often confused. Indeed, low friction is not necessarily low wear, e.g. early PTFE
THR low friction but high wear. On the other hand, non-lubricated steel has high
friction but low wear.
Wear is the erosion of material from a solid surface by the action of another solid. Four
main were processes are found.
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a. Modes of wear
Abrasive wear this happens when the material is removed by contact with
hard particles. The particles may either be present at the surface of a second
material or exist as loose particles between two surfaces. Abrasive wear can be
measured as loss of mass.
Adhesive wear it is also known as scoring, galling or seizing. It happens when
two solid surfaces slide over one another under pressure.
Fatigue wear it is a process by which the surface of a material is weakened by
cyclic loading, which is one type of general material fatigue
Three-body wear the removal of material is due to the inclusion of a third
material between the two layers.
b. Archards Wear Factor
Archards wear factor is defined
in the formula below, with the
variation of Archards constant k
shown in the figure on the right.
=
where W is load and S is the
sliding distance.
There are two ways to minimise
wear; you can make the patient
lighter or reduce the sliding
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5. Metal Wear
Metal wear occurs as it occurs with polyethylene, adding fretting and corrosion.
72
73
3. Metal-on-Metal
Metal-on-metal was a good bearing combination, which was popular in early days. For
this system, the hydrodynamic lubrication is increased, which will provide tight radial
clearance with large diameters. Hard material are also used (CoCr alloy), e.g.
Birmingham Hip Resurfacing (BHR). This type of joint is better when operated in full
fluid film to make the joint float.
a. BHR Effect of Radial Clearance
The effect of radial clearance is shown in the two graphs above. The title of the graphs
determines the diameter of the femoral head. If R is smaller, you are reducing the wedge
angle, which provides a greater area to support but less pressurisation. The graphs show
the predicted separation between the two sides of the joint.
For the graph on the left, the optimal radial clearance will be at 20 microns, which is
very hard to get. This is the main reason to explain the unsuccessful use of metal-onmetal. For the graph on the right, the diameter of the head is increased, which reduces
the manufacturing challenge. This increases the chances of getting it right.
b. BHR Stribeck Curves
The graph on the left shows the results for a
pre-wear friction test, right as they were
taken out of packaging. It can be observed
that, as cycles of wear are applied (1, 2 and 3
million), the joint matures and performs
better. After 1 million, the joint is still in
mixed lubrication. After 2 and 3 million, the
joint moves towards full fluid film
lubrication. The viscosity was changed
74
For the figure on the far right, two different materials are used. A stiffer polymer is
placed at the bottom, which is clipped into the base plate that goes into the bone. A
softer polymer is placed on top. The idea is to try and mimic the real behaviour of the
biological joint. However, it has never been used in humans.
Two main characteristics are applicable to this technique: biomimetic and
elastohydrodynamic lubrication.
The contact area increases if you have soft
material. Indeed, once the joint starts rotating,
the contact area increases, as it can be seen in
the figure on the left.
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As can be extracted from the data above, particle size comes down, but particle number
increases. These particles diffuse out in your body because the immune system does not
detect them due to their size. There is a general concern regarding its side effects in the
long-term because they are still unknown.
8. Problem Solved?
Several issues are encountered:
76
9. Problem Created?
XLPE is prone to fatigue, although wears very little. Sequential cross-linking &
annealing can give good wear and improved fatigue performance.
77
Toxicodynamic considerations
o Release of toxic compounds
Ions from metal corrosion, leachates from polymers
Hypersensitivity
o Allergy and intolerance
o Allergy Types I to IV
Type I mediated by IgE
Type IV delayed type (>12 hours to develop)
2. Measuring Biocompatibility
Assay methods
o Direct contact test
Material placed directly on the cells
o Agar diffusion
Cells grown in agar, biomaterial placed on top
o Elution
Solvent used to extract
Record cell death / health
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3. Natural Materials
The patient may be progressing well, or may be reporting pain in the groin or
anterior trochanteric area
Patient may have increase thigh pain
Patient may have significant pain when starting to walk, or buttock pain after
rising from seated position
X-ray may show possible migration of the component
79
At 3 months post-op:
A line around the acetabular component and possible migration can be seen
sometimes only on Lauenstein lateral x-ray, not AP x-rays
What sort of immune reaction was this? How could that help direct you to the cause?
Mineral oil leakage was found into coolant for machinery. The contamination was not
removed at the solvent wash stage. This residue causes DHT.
80
81
a. Manufacturing Processes
Four different types of Consolidation process are used to manufacture UHMWPE:
82
The graph below shows the different steps of the manufacturing process for UHMWPE.
You can vary pressure and temperature during the consolidation process. This will
modify the degree of crystallinity produced. Manufacturers usually change these two
parameters to differentiate their products.
b. Surface Properties
Hydrophobic surface
Differing roughness depending on
manufacture
Surface may be passivated (not clinically
applied)
c. Biostability
Essentially inert
o No biodegradation
o Limited oxidation (more dependent on shelf-life)
Immune response is muted
o Fibrous encapsulation
Only for bulk material
d. Sterilisation
Normally, high-pressure steam will be used to sterilise an object. However, this is not
appropriate for polymers. Several methods are available:
Ethylene Oxide gas (ETO) has been a commercially available sterilisation method
since the 1980s. Highly toxic, ETO neutralises bacteria, spores and viruses. UHMWPE
is a good candidate for ETO sterilisation because it contains no constituents that will
react with or bind to the toxic gas.
Low-temperature gas plasma is relatively a new commercially available sterilisation
method that was applied to UHMWPE in the 1990s. Gas plasma is a surface sterilisation
method that relies upon ionised gas for deactivation of biological organisms. Two
plasma methods are used: peracetic acid gas plasma or hydrogen peroxide gas plasma.
Starting in the 1960s, UHMWPE components for joint replacement have been stored in
air-permeable packaging and gamma sterilised with a nominal dose of 25 kGy (2.5
Mrad)(see graph below). Although the packaging of orthopaedic implants has evolved
during the past 30 years, gamma sterilisation of UHMWPE components remains an
industry standard today. Historically, UHMWPE components have received a dose
ranging between 25 and 40 kGy during sterilisation. Two methods are available:
83
In air
In inert gas this breaks the links of the different polymer fibres (see figure
below)
o Nitrogen, argon
3. Polymethyl-methacrylate (PMMA)
This is a widely used polymer material in many applications, such as bone cement,
intra-ocular lenses and dentures & dental moulds. The table shows the properties of
different PMMA polymers.
a. Biostability
These materials are biodegradable, following a hydrolytic process:
We often use a copolymer, which involves putting different monomers into a polymer
chain.
b. Mechanical Properties
Mechanical properties change
over time due to the degradation
of the polymer. The flex-strength
can be up to 200-250 MPa with a
modulus of 12-15 GPa. The graph
on the left shows the strength and
mass of the polymer over time. It
is clear that strength declines
faster than mass. The hydrophobic nature means that it tends to degrade from the
surface so you maintain a strong core.
An example of copolymer is shown in the left. Once
screwed, you tear off the head. It is used to screw bits
of bones (e.g. hand bone) that do not get huge amount
of load. The plastic would lose strength as bone heals,
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giving stable fixation early in the healing process. It is also used in birth control
implants.
5. Case Study Implanon
Implanon is a single-rod implant, with a length of 4cm and a diameter of 2mm. It
contains 68mg of etonogestrel. It is basically an Ethylene Vinyl Acetate (EVA) carrier,
i.e. low Youngs modulus, flexible and less palpable. The manufacturing process is as
follows:
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It is important to remember that the mass difference is not important in most medical
cases for the components (i.e. in terms of body weight). The next table provides
properties of several metallic biomaterials.
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When considering surface properties of metals, the main factors to be considered is the
hardness / ductility. Hardness is important when you are making smooth components
(e.g. femur head). For different materials:
SS: HV 275-300
Ti-6Al-4V: HV 360-400
CoCr: high carbon HV 450-470, low carbon HV 430-460
The picture on the left represents the femur head as it was put in and the right figure is
an image of the same femur head taken out later with the scratches due to the service.
Since the metal is a ductile material, it can self-heal to some
extent because the metal keeps moving. The two bumps
represented in the figure on the left are damaging the other
part (non-smooth surface), but they will wear away with
time.
To provide a harder surface to the metal biomaterial, several options are available:
TiN
Diamond-like Carbon (DLC)
Oxinium
and ceramic, as seen in the figure below. The Au part is there because you need some
conductivity to help in surgery, but it is not part of the bearing surface.
a. Biostability and Biocompatibility
All the metallic biomaterials form thick, stable, oxide
layers. Hence, biocompatibility is good. Indeed,
Titanium alloys deemed to be osseointegrative, as it can
be seen in the figure. In the figure, the bone (pink) can
go all the way into the titanium (black) in a way it could
not when using other alloys.
Several osseointefration technologies are available:
Texturing encourages bone to grow into the material, e.g. the knee joint has
below this porous coating so bone can grow into it
o Porous coating, sintered beads
o Wire mesh coating
Hydroxyapatite coating
Titanium wires used to create a metallic mesh, since you
cannot do beads with titanium because of its welding
properties. There are problems with both the beads and the
mesh since they have lower strength. Therefore, you get
more degradation, with the possibility of the material
chipping away.
Tissue attachment bioceramics these will degrade with time, promoting tissue
growth
o Hydroxyapatite coating
o Bioactive glass
o Tricalcium phosphates
Articular bioceramics
o Composition
Zirconia, ZrO2
Alumina Al2O3
Alumina matrix composite
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Surface area increases (powders > porous solid > dense solid)
Crystallinity decreases
Crystal perfection decreases
Crystal and grain size decrease
There are ionic substitutions of CO32-, Mg2+ and Sr2+ in HA
b. Articular Bioceramics
In the 1970s, early alumina ceramics were used. This design shown poor quality and
design flaws. Indeed, brittle failures were very common, up to 15%. This is not a
surprising to an engineer since ceramic material will have brittle failure under this kind
of load.
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The following material used was Ceramtec, De. In fact, 2.5 million alumina femoral
head were manufactured. In the old days, the cup had 90-degree edges; nowadays you
have radii. This is difficult to manufacture because you cannot machine a ceramic after
it is made. Therefore, you need to improve the manufacturing processes completely.
Using biolox femoral heads, the percentages of fail rates were:
In the last 40 years, engineers have come a long way; ceramics nowadays are very
unlikely to fail brittly. This is due to improvements in both manufacturing processes and
design.
Contemporary ceramic biomaterials are currently used. Zirconia was introduced in the
mid 1980s as part of the new era, with a hardness of HV1270. Zirconia properties
decline due to the sterilisation process. Even in the short time, the sterilisation process
reduces its performance.
Alumina 3rd generation had a hardness of HV2000
and a grain size of 1.8 microns. The graph on the left
shows the impact of the sterilisation onto three
materials: biolox delta (alumina matrix composite),
zirconia and biolox (alumina).
Phase instability was found in Zirconia, which leads to surface roughening. When you
manufacture zirconium, whole grains can change structure. The figure on the left shows
zirconia as manufactured. The right one shows the same material after some wear,
where the change in grain structure can be observed.
Zirconia ceramics have three phases of crystal structure, which transform according to
temperature. The monoclinic phase transforms into a tetragonal phase at less than
1100C, while the tetragonal phase transforms into the cubic phase at 2370C. Since the
tetragonal phase is unstable, but shows the greatest mechanical strength of the three
phases, Y-TZP was used for the surgical grade zirconia ceramics. Transformation from
the tetragonal phase into the monoclinic phase brings a 3% increase in the volume of
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ceramics. While this phase transformation plays an important role in increasing the
mechanical strength of Y-TZP, when it occurs extensively it may cause an increase in
the surface roughness. Phase transformation in Y-TZP is induced at a relatively low
temperature in the presence of water and pressure. Therefore, sterilisation of Y-TZP in
an autoclave is contraindicated.
4th generation Alumina was an alumina matrix composite is called Biolox delta,
consisting of ~75% alumina, 24% zirconia and other trace elements. The pink colour is
due to the chromium oxide (Cr2O3), with a hardness of HV 1950. This material is very
tough because of the grain structure. Plate-like grains help bind all the grains together.
ETO
Gas Plasma
Autoclaving (pressurised steam at 170C)
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External forces
Inertial forces
Gravitational forces
Mass
Length moment of arms
Position of centre of mass
Distribution of mass radius of gyration
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4. Gait
Flat is most efficient but demands more knee flexion. Gait is compromise to minimise
effort required.
Gait analysis includes 3D motion tracking systems, reaction plates and goniometers.
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interphalangeal joint; and between the proximal and the intermediate phalanges you find
the proximal interphalangeal joint.
2. Circulation / Innervation of Hand
The thumb is very
important because of
its functionality.
However, the hand
feels due to the huge
amount of nerves.
The most important
part that you don not
want to damage is
the bottom middle
part of your palm,
since that is where
your median nerve is.
The yellow line going through the middle of
the arm is the nerve that goes through the
carpal tunnel whereas the yellow line on the
left of the arm is the nerve that goes around it.
Regarding the muscles of the thumb, most of
these muscles come down from the arm. That
is why you can feel them in the arm when
moving your thumb.
3. Ligaments of the Finger
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The ligaments in the hand act much more like actual hinges. The side-to-side movement
of the fingers is restricted by the collateral ligaments, especially in the proximal and
distal interphalangeals.
The bollar ligaments (acting as cables in a bridge) and groove help to keep the volar
ligament in place. This system allows the finger to flex and bend.
4. Muscles & Tendons of the Hand
5. Wrist Motion
The motion of wrist can be divided into:
Flexion / extension
Adduction / abduction
Supination / pronation (figure on the left) it is
interesting to see that when you flip your hands, the
bones in the arm go from parallel to crossed.
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6. Grips
7. Tendon Biomechanics
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8. Finger Forces
Retinacular ligaments and tendon sheats
are responsible for the forces in the
fingers. Tendon sheats are the membrane
that act as a guide of the tendons,
although it also lubricates so the tendon
can slide easily (A-1). The retinacular
ligament is represented by C-1.
The symptoms include swelling in the region of the carpal tunnel. You get numbness
and pain, and maybe also tingling/needle sensation. This syndrome is associate with
repetitive injury to your hand.
10. DeQuervains Tenosynovitis
This is the inflammation of the abductor pollicis longus and extensor pollicis brevis
tendons. The predisposing factors for this disease are:
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Repetitive action
o Grip, squeeze, wringing
o Force >4kg
o Cold, gloves
o Vibration
The condylar structure of the MP joint, which permits motion in 2 planes, makes the
MP joint inherently more unstable than the IP joints; therefore, the distorting effects of
RA are more pronounced. The classic deformities associated with RA of the MP joints
are ulnar drift, which is made up of ulnar shift and ulnar deviation, and volar
dislocation. The cumulative effects of various factors contribute to these deformities.
Initially, the MP capsule and ligamentous structures are stretched by the proliferation of
the synovium, which loosens the collateral ligaments and decreases joint stability.
Normally, in the flexed position, minimal lateral movement occurs at the MP joint, but,
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reflected radially. Care is taken to not breach the integrity of the capsule at this time. An
incision is made longitudinally in the capsule of the MP joint. Using a periosteal
elevator, the metacarpal head is freed of any soft tissue attachments to the metaphyseal
flare.
Using an oscillating saw, a true cut is made, maintaining 90 in line with a long access
of the metacarpal and in the coronal plane. The metacarpal head is then discarded. An
electrical burr or a Christmas-tree type of rasp can be used to ream the medullary canal.
The medullary canal of the proximal phalanx is then identified through a burr hole on
the articular surface of the base of the phalanx. Osteophytes are removed from the
proximal phalanx at this time with a rongeur. The intramedullary canal of the proximal
phalanx is reamed. Care is taken so that the rectangular opening for both the metacarpal
and the proximal phalanx are square in line with the axial direction of both the
metacarpal and phalanx. Appropriate sizes are then placed inside the medullary canals.
Using a no-touch technique, the definitive prosthesis is then introduced. The capsule is
repaired, and the extensor tendon is subsequently aligned. Some authors prefer to
reconstruct the collateral ligaments at this time. Care is taken at the initial dissection to
preserve as much of the collateral ligament as possible. The skin is then closed using
nylon suture, and a splint is applied with the fingers in extension and in a neutral
position.
Approximately 4-5 days after the procedure, the patient is fitted for a dynamic outrigger
splint that maintains extension in an appropriate anatomical position of the fingers while
the patient undergoes active flexion exercises. Night splints are manufactured to
maintain the fingers in extension. Splinting is required for the next 4-8 weeks. Followup radiographs are obtained to confirm the appropriate positioning of the implants.
Crossed intrinsic transfer of the extensor tendons from the ulnar side to the radial side of
the adjacent finger to increase stability is another surgical option. Intrinsic release to
alleviate intrinsic tightness eliminates the dorsal digital expansion tightness that is one
of the subluxing forces on the MP joint. Finally, MP joint arthroplasties can provide
long-term relief. A patient with good hand function in the absence of pain is not a
candidate for arthroplasty, even if obvious MP joint deformity is present, because
surgery may not improve the hand function and could decrease grip strength.
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The simulator successfully recreated the failure mode observed in the Swanson MCP
joint.
b. Two-piece MCP joint
A two-piece replacement was introduced, with
resurfacing prostheses and made of ascension,
PyroCarbon material.
The characteristics of this model are show in the table below.
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Tissue Engineering is all about encouraging the body to repair/heal itself. Instead of
replacing something with a big intervention, we repair a patch by growing a new piece
cartilage.
It also helps reduce the scarcity of organ donors (skin, heart, kidney, liver, etc.).
3. Tissue Engineering Origins
The First Generations (1950s) goal was Bionertness, which means trying to create a
man-made material that you can put into the body and that the body will just integrate.
There will a minimum reaction from the body to the presence of the biomaterial.
The Second Generations (1980s) goal was Bioactivity, i.e. materials that can be
integrated in the body, and the body will grow around and in it and, after, the
biomaterial will be replaced by actual bone. This include resorbable materials that will
have a controlled reaction with physiological environment.
The Third Generations (2000s) goal is regenerate functional tissue. The concept of
re-growing tissue is main concept including in this third generation. There is a lot of
optimism but it still remains as an ambition rather than a real thing (very few products).
These Third Generation materials main characteristics are: biointeractive, integrative,
resorbable; stimulate specific cell response at molecular level.
4. Tissue Engineering Paradigm
There are three approaches to the use of tissue engineering:
Cell injection method You can just inject stem cells into a damage part of the
body and the cells will manage the healing process better.
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Closed system method you have the cells encapsulated in something. The
encapsulation process is a process of bidirectional trafficking of small
molecules, but protect cells from effector agents of immune system
(complement).
o Extravascular capsules
o Macrocapsules
o Microcapsules
Tissue Engineering using scaffold biomaterials hard-core version of tissue
engineering.
5. Scaffold Paradigm
To use scaffold
materials, there are two
things you need: cells
and scaffold.
A scaffold is a three
dimensional piece of
material which you can
saw cells into. Cells like
to grow on surfaces;
they like to be attached
to something. IF you
take those cells and you
try to grow them in the
lab, they are much
happier if they grow on
something, the scaffold. From an tissue engineering point of view, were going to take
the scaffold and we are going to make it into a piece of new tissue. The scaffold is going
to form part of the device we are going to implant. You manufacture the scaffold to be
the right kind of thing for the thing we want to do. For example, to re-grow cartilage,
we need scaffold that has the right architecture, etc.
We will then put the stem cells into the scaffold and hope that ultimately they become
cartilage cells. We need to make sure that the cells get all the right signals to turn them
from stem cells into cartilage cells.
The signals we are interested in are mechanical properties, right biological reactions,
right architecture, right nutrients, etc. Ultimately what we want to happen is that our
scaffold with the cells on it, over time, will no longer be there. It will be a natural piece
of cartilage. Therefore, the scaffold needs to be resorbable, i.e. replace by natural
materials.
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Maturation in bioreactor refers to taking scaffold and cells and letting them grow in the
lab.
The tissue engineering market is very significant, with $1.5 billion in 2008. It is
projected to grow at a 16.2% compound annual rate from 2008 through 2013, therefore
approaching $3.2 billion by 2013. This market is driven by the expectations that tissue
engineering will be able to replace many of the things that are currently manufactured
and used as devices.
6. Stem Cells
Stem cells are those cells are able to
generate other types of cells. It is a
vey basic type of cell but also a very
powerful type of cell. These cells are
highly used for tissue repair and
tissue maintenance.
At first, there was some ethical
controversy due to the fact that stem
cells had to be taken from the
embryo. Two options are available:
you can take it from the embryo or
you can make them in the lab.
Some workers have taken very early human embryos (a few days old), allowed the
embryo to develop a few more days, and removed the inner cells destined to form the
embryo; these cells in culture form embryonic stem cells or ES cells. Because they
are derived so early in development, they are said to be totipotent, i.e. totally potent to
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form any specific cell type in the body, or sometimes termed pluripotent, i.e. able to
form many potential specific cell types.
While this is a tantalising source of stem cells, it is perhaps because of this unlimited
potential and the numerous development signals needed to become a specific cell type
that it is also may be a less controllable source. A study with mouse embryonic stem
cells indicates that at times, these cells, when injected into mice, form tumours
(teratocarcinomas).
Another source of human embryonic stem cells is later human embryos, from 5-9 weeks
old. The primordial germ cells from these embryos (cells destined to form the egg or
sperm cells in the adult) also can form embryonic stem cells in culture. However, use of
these cells for treatment of disease or organ generation, as well as the use of embryonic
stem cells from early human embryos as proposed by NIH, faces a major hurdle
immune rejection. Even early embryonic cells already have the molecules on their
surface that lead to an immune response in the host, or even a response of the transplant
against the host (graft vs. host disease).
Thus, use of embryonic stem cells for tissue regeneration faces the same problem as
normal organ transplants. The body of the person receiving the embryonic stem cells
will reject them, unless large doses of toxic immunosuppressive drugs are used. One
way to avoid this problem might be to form a clone of the pation (but of course this
procedure is also highly controversial); the embryonic stem cells from this procedure
would not be rejected.
b. Adult (somatic) Stem Cells
Other stem cells are found in somatic tissues and are called either somatic stem cells or
adult stem cells. These stem cells are multipotent, i.e. they are committed to give rise to
cells that have a particular function. Examples of somatic stem cells include:
Most if not all tissues and organs contain a small number of undifferentiated cells that
can differentiate into the major cell types of the tissue or organ.
Induced pluripotent cells (iPSCs) push them backwards in time to become more basic
and powerful.
The tissue engineering process using iPSCs is shown in the figure below.
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7. Scaffolds
There are several factors that affect the degradation rate:
Polymer chemistry
o Composition, structure, molecular weight, chain motility,
impurities/additives
Scaffold structure
o Density, shape, size, surface texture, surface to volume ratio, pore size,
wettability, sterilisation
In vitro
o pH, temperature, ionic strength, mechanical loading, etc.
In vivo
o Vasculature, tissue, mechanical loading, enzymes, etc.
a. Materials
Open scaffold
o Cell seeding cells can get into it
o Nutrient perfusion nutrients can then get into it
o Control of resorption rate (surface-volume ratio)
Mechanical properties
o Bulk properties
o Time dependency
Static culture
Spinner flask culture
o Scaffolds suspended in media, mixed by stirrer bar
Rotary vessel culture
o Media is mixed by rotating whole vessel
Perfusion culture
o Continuous media flow pumped through scaffold
o
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3D
Printing
The structures are based on the solid freedom fabrication concept:
3D printing
Stereolithography
Selective laser sintering