Bioelectricity - refers to the electrical

phenomena of life processes, and is a

parallel
to
the
medical
subject
electrophysiology.
Biopotentials - a voltage produced by a
tissue of the body, particularly muscle tissue
during a contraction.
Electrophysiology - The biomedical field
dealing with the study of electric activity in
the body. Electrophysiology includes the
study of the production of electrical activity
and the effects of that electrical activity on
the body.
A. Historical perspective:
Bioelectricity first discovered by Luigi
Galvani in 1780s
Originally termed animal electricity
Galvani thought that a special
electrical fluid was prepared by the
brain, flowing through the nerve tubes
into muscles
B. Modern perspective:
Bioelectricity is now known to obey
the same fundamental laws of
electricity
in
the
atmosphere,
conducting wires, semiconductors, etc.
However, there are some substantial
differences
between
bioelectrical
systems and man-made electrical
systems.
Comparison of bioelectricity and
man-made electrical systems:

Man-made
electrical
systemsCharge carriers are electrons within a

conductor ; Current flow within

(insulated) conductors
Bioelectricity -Charge carriers are
ions within an electrolyte ; Current
flow inside and outside of (partiallyinsulated) cell membranes
Membranes
Bioelectricity has its origin in the
voltage differences present between
the inside and outside of cells. These
potentials arise from the specialized
properties of the cell membrane,
which separates the intracellular from
the extracellular volume. Much of the
membrane surface is made of a
phospholipid bilayer, an electrically
inert material. Because the membrane
is thin (about 75 ), it has a high
capacitance, about 1F/cm2.
One basic mechanism is the energyconsuming cell membrane ion pumps
polarizing a cell, and the action
potential generated if the cell is
triggered and ion channels opened.
The depolarization process generates
current flow also in the extracellular
volume, which again results in
measurable biopotential differences in
the tissue. An important part of such
activity is the intracellular and
extracellular single cell measurement
results in microelectrodes. Single
neuron
activity
and
signal
transmission can be studied by
recording potentials with multiple
microelectrode arrays.
Conduction Along an Intracellular
Path
Flow of electricity along a nerve or
within a muscle occurs passively
through the conducting medium inside
the cell. The nature of the intracellular
current path is closely related to the
function of the current within that kind
of cell. Nerve cells may have lengths
of a meter or more, so intracellular
currents can flow unimpeded and
quickly throughout this length.
Conduction Along an Extracellular
Path
Current flow outside of cells is not
constrained to a particular path but
rather flows throughout the whole
surrounding conducting volume (the
volume conductor), which may be the

whole body. Currentintensity is highest

near the places where current enters
or leaves cells through the membrane.
Current flow from bioelectric sources
through
the
volume
conductor
generates small potential differences,
usually with a magnitude of a millivolt
or less, between different sites within
the volume or on the body surface.
Electrical Activity at Cellular Level
Source of bioelectric potentials
electrochemical activity of a certain
class of cells known as excitable cells
Excitable Cells
Cells that can generate electrical
potentials and currents are referred to
as excitable cells.
These potentials and currents can be
observed in the cells interior volume,
across their membranes, and in their
surrounding conducting volume.
Excitable cells include:
nerve cells (neurons),
muscle fibers, and
sensory receptor (transducer) cells
Electrical State of Excitable Cell
Resting State/Resting Potential
Action State/Action Potential
CELL MEMBRANE POTENTIALS
Cell Membrane
very thin (7-15 nm) lipid-protein
complex
transmembrane ion channels (pores)
allow flow of ions across the
membrane
like a leaky capacitor: a thin dielectric
material acts as a charge separator
impermeable to intracellular protein
and other organic anions
selectively permeable to sodium (Na+)
potassium (K+) and chlorine (Cl-) ions
ion concentration difference across
membrane creates a diffusion gradient
ions flow, creating an electric field that
opposes flow, until an
equilibrium is established
similar to p-n junction, ions flow by
diffusion and create a potential
difference which inhibits further flow
of charged ions
RESTING STATE
All cells (not just excitable cells) have
a resting potential: an electrical

charge across the plasma membrane,

with the interior of the cell negative
with respect to the exterior. The size of
the resting potential varies, but in
excitable cells runs about 70
millivolts (mv).
excitable cells maintain a steady
electrical potential difference between
the
internal
and
external
environments (-50 to -100 mV)
membrane is
slightly permeable to sodium ions
(Na+)
freely permeable to potassium and
chlorine ions (K+, Cl-)
The resting potential arises from
two activities:
The sodium/potassium ATPase.
This pump pushes only two
potassium ions (K+) into the cell
for every three sodium ions (Na+)
it pumps out of the cell so its
activity results in a net loss of
Positive charges within the cell.
Some potassium channels in the
plasma
membrane
are
"leaky"
allowing a slow facilitated diffusion of
K+ out of the cell (red arrow).

MEMBRANE ION FLOW

Maintaining
steady
state
ionic
imbalance
requires continuous transport of ions
against electrochemical gradients
Active transport mechanism located in
the membrane
the sodiumpotassium pump
actively transports Na+ out of cell and
K+ into cell in the ratio 3Na+: 2K+
associated pump current iNaK is a net
outward current that tends to increase
the negativity of the intracellular
potential
energy for the pump is provided by a
common source of cellular energy,
adenosine
triphosphate
(ATP)
produced by mitochondria in the cell

Factors influencing the flow of

ions across the membrane
diffusion gradients
inwardly directed electric field
membrane structure (availability of
pores)

active transport of ions against an

established electrochemical gradient

CELL MEMBRANE POLARIZATION

Three states of cell membrane
polarized: the cell membrane is at a
steady resting potential
depolarized: when the magnitude of
membrane potential decreases(from
negative/rest value)
hyperpolarization:
increase
in
magnitude of membrane potential
Return to resting state
repolarization: return to membrane
equilibrium after action potential
ACTION POTENTIAL
Action
potential:
brief
transient
disturbance of membrane potential
change in membrane potential due to
a
stimulus
adequate
to
bring
depolarization sufficient to exceed its
threshold potential and thereby elicit
an all-or-none action potential
change in potential from resting level
a certain amount (of potential) for a
fixed duration of time
for example: a nerve fiber, v 120
mV and the duration is 1 ms
further increases in intensity or
duration of stimulus beyond that
required for exceeding the threshold
level produce only the same result
Absolute refractory period
membrane cannot respond to any
stimulus no matter how intense
Relative refractory period
action potential can be elicited by an
intense superthreshold stimulus
Set upper limit action potential
frequency
EX: for nerve axon with absolute
refractory period of 1 ms max action
potential frequency is 1000 impulses/s
but, typical neuron firing rate is ~30
Hz
ELECTROPHYSIOLOGY OF THE MUSCLE
ELECTROMYOGRAM (EMG)
EMG detects the electrical potential
generated by muscle cells activated
electrically or neurologically
composed
of
superimposed
motor unit action potentials

(MUAPs) from several motor

units
Motor unit
a single motor nerve fiber and
the bundle of muscle fibers
smallest unit of skeletal muscle
that can be activated
Single motor unit (SMU) is a bioelectric
source located in a volume conductor
consisting of all other muscle fibers
The evoked field potential from the
active fibers of an SMU
has a triphasic form of brief
duration (3 to 15 ms)
amplitude of 20 to 2000 mV
frequency of discharge varies
from 6 to 30 per second
EMG results are often necessary
to help diagnose or rule out a
number of conditions such as:
Muscle
disorders, such as
muscular
dystrophy
or
polymyositis
Diseases
affecting
the
connection between the nerve
and the muscle, such as
myasthenia gravis
Disorders of nerves outside the
spinal cord (peripheral nerves),
such as carpal tunnel syndrome
or peripheral neuropathies
Disorders that affect the motor
neurons in the brain or spinal
cord, such as amyotrophic
lateral sclerosis or polio
Disorders that affect the nerve
root, such as a herniated disk in
the spine
ELECTROPHYSIOLOGY
OF
THE
HEART
ELECTROCARDIOGRAM (ECG)
Electrocardiogram:
measures
potentials on body surface due
to neuromuscular activity of the
heart
ideally,
but
often
see
interference
from
other
neuromuscular activities
Source of ECG signal
electrical activation sequence of
the hearts ventricle leads to
production of closed-line action
currents that flow in the
thoracic
volume
conductor
leading to

considered a purely passive

medium containing no electric
sources or sinks
potentials that can be measured
on the outer surface of the
medium
An ECG/EKG is done to:
Irregularities in your heart
rhythm (arrhythmias)
If blocked or narrowed arteries
in your heart (coronary artery
disease) are causing chest pain
or a heart attack
Structural problems with your
heart's chambers
A previous heart attack
How well ongoing heart disease
treatment,
such
as
a
pacemaker, is working
Diseases diagnosed by ECG:
Enlargement of the heart
Congenital
heart
defects
involving
the
conducting
(electrical) system
Abnormal rhythm (arrhythmia)
rapid, slow or irregular heart
beats
Damage to the heart such as
when one of the hearts arteries
is blocked (coronary occlusion)
Poor blood supply to the heart
Abnormal position of the heart
Heart
inflammation

pericarditis or myocarditis
Cardiac
arrest
during
emergency room or intensive
care monitoring
Disturbances of the hearts
conducting system
Imbalances
in
the
blood
chemicals (electrolytes) that
control heart activity.
ELECTROPHYSIOLOGY
OF
VISION
ELECTRORETINOGRAM (ERG)
When retina is stimulated with a
brief flash of light
characteristic
temporal
sequence
of
changes
in
potential can be recorded
between
exploring electrode (placed on
inner surface of retina or on the
cornea)
and an indifferent electrode
placed elsewhere on the body

These potential changes are

collectively
known
as
the
electroretinogram (ERG)
they are clinically recorded with
the aid of an Ag/AgCl electrode
embedded in a special contact
lens
Conditions
diagnosed
by
ERG
retinitis pigmentosa,
retinitis punctata albescens,
retinitis
pigmentosa
sine
pigmento
related
hereditary
retinal
degenerations,
disorders that mimic retinitis
pigmentosa,
Leber's congenital amaurosis,
choroideremia,
gyrate atrophy of the choroid,
gyrate atrophy of the retina,
Goldman-Favre syndrome,
congenital
stationary
night
blindness,
X-linked juvenile retinoschisis,
achromatopsia,
cone dystrophies, and
Usher syndrome

ELECTROPHYSIOLOGY OF THE NEURONS

ELECTRONEUROGRAM (ENG)
ENG measures electrical activity of
neurons in the central nervous system
(brain, spinal cord) or peripheral
nervous system (nerves, ganglions)
done by placing an electrode in
the neural tissue to record
neuron action potential or one
or a group of neurons
ENG can measure conduction velocity
in a peripheral nerve
done by stimulating motor
nerve at 2 points a known
distance apart and recording
difference in arrival time at
measurement point
conduction velocity can show
nerve regenerating following
nerve injury
ELECTROPHYSIOLOGY OF THE BRAIN
ELECTROENCEPHALOGRAM (EEG)
EEG measures potential fluctuations
recorded from the brain

Brain electrical activity recorded with

three types of electrodes
scalp - electrode cap, relatively
far from the brain, traditional
EEG
Cortical - electrodes are placed
on the exposed surface (cortex)
of the brain; recording is called
an electrocorticogram (ECoG)
depth
electrodes
thin
insulated
needle
electrodes
placed into the neural tissue of
the brain; often called neural
probes
o surprisingly little damage
to the brain tissue using
micro-electrode arrays
Recorded
fluctuating
potentials
represent a superposition of the field
potentials produced by a variety of
active neuronal current generators
within the volume conductor medium
although neural probes can
record single neuron events
Signal intensity: EEG activity is quite
small, measured in microvolts (mV).
Signal
frequency:
the
main
frequencies of the human EEG waves
are:
Delta: has a frequency of 3 Hz
or below. It tends to be the
highest in amplitude and the
slowest waves
Theta: has a frequency of 3.5
to 7.5 Hz and is classified as
"slow" activity
Alpha:
has
a
frequency
between 7.5 and 13 Hz
Beta: beta activity is "fast"
activity. It has a frequency of 14
and greater Hz
Biomaterials
and
Engineering
Russell Aaron S. Tolentino

Tissue

MATERIALS
IN
MEDICINE:
FROM
PROSTHETICS TO REGENERATION

Biomaterials
use
increased
rapidly in the late 1800s, particularly
after the advent of aseptic surgical
technique by Dr. Joseph Lister in the
1860s.

The term asepsis often refers to

those practices used to promote or

induce asepsis in an operative field in

surgery or medicine to prevent
infection.

The first metal devices to fix

bone fractures were used as early as
the late eighteenth to nineteenth
century; the first total hip replacement
prosthesis was implanted in 1938; and
in the 1950s and 1960s, polymers
were
introduced
for
cornea
replacements and as blood vessel
replacements.

There
are
still
many
unanswered questions regarding the
biological response to biomaterials
and the optimal role of biomaterials in
tissue regeneration that continue to
motivate biomaterials research and
new product development

Over most of history, minimal

understanding
of
the
biological
mechanisms of tissues meant that the
biomedical engineering approach was
to completely replace the tissue with
lost function with a simple biomaterial.
As our understanding of tissues,
disease, and trauma improved, the
concept of attempting to repair
damaged tissues emerged

The notion of a biomaterial has

evolved over time in step with
changing medical concepts. Williams
in 1987 defined a biomaterial as a
nonviable material used in a medical
device, intended to interact with
biological systems.

The expectations for biomaterial

function
have
advanced
from
remaining relatively inert in the body
to being bioactive and assisting with
regeneration. Bioactive materials have
the capability to initiate a biological
response after implantation such as
cell adhesion, proliferation, or more
excitingly, the differentiation of a stem
cell leading to regeneration of a
damaged tissue or whole organ.
BIOMATERIALS: PROPERTIES, TYPES,
AND APPLICATIONS
Mechanical
Properties
and
Mechanical Testing

The most common way to

determine mechanical properties is to
pull a specimen apart and measure
the force and deformation. Materials

are also tested by crushing them in

compression or by bending them.

The vast majority of those used

in the biomaterials field are from the
American Society for Testing and
Materials (ASTM). For example, tensile
testing of metals can be done
according to ASTM E8, ASTM D412 is
for rubber materials, and ASTM D638
is for tensile testing of rigid plastics.

Several other terms are applied

to the test results. The slope of the
elastic portion, the elastic modulus, is
often called stiffness. If the metal
stretches a great deal before failure it
is said to be ductile. If the material
does not deform or yield much before
failure, it is said to be brittle. The area
under the curve has u is called
toughness. Stronger materials are
typically harder. Hardness is tested by
measuring the indentation caused by
a sharp object that is dropped onto the
surface with a known force. Hardness
is perhaps the most important
property
when
considering
a
materials wear resistance.

An additional property that is

not depicted in the figure is the
fatigue strength or endurance limit of
a material.

An additional property that is

not depicted in the figure is the
fatigue strength or endurance limit of
a material.

Clearly, fatigue strength is a

critical property in the design of loadbearing devices such as total hips
which are loaded on average a million
times a year or heart valves which are
loaded 40 million times a year.
Metals
Metals used as biomaterials have high
strength and resistance to fracture
and are designed to resist corrosion.

The advantages of metals over other

materials such as ceramics and
polymers are that they are strong,
tough, and ductile (or deformable,
particularly as compared to ceramics).
Disadvantages include susceptibility to
corrosion due to the nature of the
metallic bond (free electrons).
Ceramics and Glasses

The advantages of the class of

materials known as ceramics are that

they
are
very
biocompatible
(particularly with bone), are inert,
have low wear rates, are resistant to
microbial attack, and are strong in
compression.
Some disadvantages include
brittleness, the potential to fail
catastrophically, and being difficult to
machine.
Certain
compositions
of
ceramics, glasses, glass-ceramics, and
composites have been shown to
stimulate direct bone bonding, which
is important in securing orthopedic
medical devices such as replacement
hips and knees and spinal fusion
devices.

Polymers

Polymers are well suited for

biomedical applications because of
their diverse properties. For example,
polymers can be flexible or rigid, can
be low strength or high strength, are
resistant to protein attachment or can
be modified to encourage protein
attachment, can be biodegradable or
permanent, and can be fabricated into
complex shapes by many methods.

Some
disadvantages
of
polymers are that they tend to have
lower strengths than metals or
ceramics, deform with time, may
deteriorate during sterilization, and
may
degrade
in
the
body
catastrophically or by release of toxic
by-products.
Natural Materials

Natural
materials
are
synthesized by an organism or plant
and are typically more chemically and
structurally
complicated
than
synthetic materials. The directional
bonds within proteins give rise to the
very high mechanical properties of
natural polymers.

Natural materials exhibit a

lower incidence of toxicity and
inflammation
as
compared
to
synthetic materials; however, it is
often expensive to produce or isolate
natural materials.

There is also variability between

lots of natural materials, which makes
it difficult to maintain consistency and

sometimes
prevents
widespread
commercial use.
Composites

Composite materials consist of

two or more distinct parts. Although a
pure material may have distinct
structural subunits such as grains or
molecules, the term composite is
reserved for materials consisting of
two of more chemically distinct
constituents that are separated by a
distinct interface.

Composites are made by mixing

two
components
and
molding,
compacting, or chemically reacting
them together.

Composites are well suited for

devices that require a combination of
properties
such
as
total
joint
replacements, dental fillings, and bone
plates.

The advantages of composites

are that the properties can be tailored
to fit nearly any application
LESSONS
FROM
NATURE
ON
BIOMATERIAL
DESIGN
AND
SELECTION
An Overview of Natural Tissue
Construction

Biomedical engineers are asked

to design medical devices or systems
that repair, monitor, or assist the
functions
of
the
human
body.
Approaches that mimic or replicate
natures
techniques,
known
as
biomimetics, are often at the heart of
a successful medical device or
therapy.
Cells Build Natural Tissues

There are over 200 different cell

types in the human body and
approximately 100 trillion cells per
person. Bone tissue alone has more
than ten types of cells:
Osteoblasts which make bone
Osteoclasts which degrade bone
Osteocytes which maintain bone
Cells in blood vessels that run through
bone [erythrocytes (red blood cells)
and immune cells (lymphocytes,
monocytes, macrophages, neutrophils,
and eosinophils)]
Lipid cells and mesenchymal stem
cells that are not yet differentiated

into a specific type of cell, which are

both found in bone marrow

Cells not only manufacture the

tissue constituents, they also maintain
the tissue and adapt the tissue
structure
to
the
changed
environments, including mechanical
load environments. Key elements in
the assembly of tissues are:

Cellcell
signaling:
Cellular
interactions are controlled by complex
molecular communication between
cells. Cell signaling molecules are
typically proteins, known as cytokines
and chemokines. Cytokines (also
called
growth
factors)
cause
proliferation (cell replication) and
differentiation. Chemokines induce cell
migration.

Apoptosis:
As
part
of
the
coordinated function of tissue growth
and morphogenesis (pattern or shape
formation)

Necrosis: In contrast to apoptosis,

another form of cell death due to
trauma or toxin is known as necrosis,
in which the cell swells and bursts,
releasing its intracellular contents.

Angiogenesis: Cells cannot survive

without a supply of oxygen and
nutrients and a way to remove waste
products. Blood vessels provide these
functions, and the lymphatics assist
with additional waste removal. The
formation of new blood vessels, or
angiogenesis, must occur rapidly
during new tissue growth or the newly
formed tissue will die or necrose.

Neurogenesis: The nervous system

consists of several cell types, neurons
that conduct electrical impulses; glial
cells that protect, support, and nourish
neurons
Hierarchical Design

Similar to a nested set of eggs or

Russian dolls, in which you open up
one just to find another smaller one
inside, natural tissues have nested
structures.
During
cell-mediated
tissue
construction, the smallest units selfassemble first, then these units selfassemble to form larger units, and
finally the larger units self-assemble.
The Wound Healing Response after
Biomaterial Implantation

The implantation of a biomaterial

creates a disruption of the anatomic
continuity of tissue and, as such,
creates a wound. The body has a
highly developed wound healing
response that is immediately triggered
by the biomaterial implantation.
Hemostasis: Platelet cells control
bleeding through coagulation by
adhering to the proteins attached to
the biomaterial surface and by
releasing clot-forming proteins.
Inflammation:
Clot
formation
induces
the
production
of
cell
signaling molecules (cytokines) that
induce
the
recruitment
of
inflammatory cells from a nearby
bloodstream.
Proliferation/initial repair: As a
result of all the growth factor signaling
by the inflammatory cells, there is a
proliferation and population of the
biomaterial with cells that can
recreate the lost or damaged tissue.
Remodeling: The rapidly formed
neotissue will be remodeled by cells
into functional tissue more similar to
the original tissue
Unlike bone, cartilage is acellular and
has a very limited capacity for repair.
Therefore, damage to cartilage is often
permanent and often progressive.

APPLICATION-SPECIFIC
STRATEGIES
FOR THE DESIGN AND SELECTION OF
BIOMATERIALS
Musculoskeletal Repair

Bone, cartilage, tendons, ligaments,

and muscles are all part of the group
of musculoskeletal tissues. Each one
must be considered individually in
terms
of
implant
design
and
biomaterials selection.

Bone is the only tissue capable of

undergoing spontaneous regeneration.
It is constantly in a state of
remodeling, always optimizing its
structure to best meet the needs of
the body. This ongoing cellular activity
is why astronauts rapidly lose bone
mass during zero gravity conditions.
Skin Regeneration

As the largest organ in human

physiology, the skin plays a vital role
in maintaining homeostasis, providing

immunity, and supporting sensory

feedback.
Cardiovascular Devices

The primary requirements for

biomaterials used for blood-contacting
circulatory applications such as heart
valves and blood vessel replacements
or stents are resistance to platelet and
thrombus deposition, biomechanical
strength
and
durability,
and
biocompatibility and nontoxicity.
Drug Delivery

Biomaterials play an important role as

delivery vehicles for pharmaceuticals
and biomolecules. The pharmaceutical
industry has long made use of
powdered biomaterials such as talc
and calcium carbonate to form pills
and tablets containing a drug.
TISSUE ENGINEERING
WHAT IS TISSUE ENGINEERING?

Tissue engineering is a biomedical

engineering
discipline
integrating
biology with engineering to create
tissues for the human body.

Translation of tissue engineering

constructs to clinical applications will
involve other scientific disciplines so
that novel engineered tissues will be
easily accepted and used by clinicians.
Bone Marrow Transplantation (BMT)

Bone marrow is the bodys most

prolific organ. It produces on the order
of 400 billion myeloid cells daily, all of
which originate from a small number
of pluripotent stem cells.
Skin and Vascular Grafts

Skin is the bodys third most prolific

tissue.
It basically consists of two layers:
(1) the dermis, the main cellular
components
of
which
are
stroma or fibroblasts
(2) the epidermis, the main
cellular components of which
are epidermal cells that are at
various stages of differentiation
into keratinocytes

This transplant technology is easily

applied to victims of burns and
patients with diabetic ulcers who have
severe problems with skin healing. To
treat these problems, skin can be
cultured ex vivo and applied to the
affected areas.

Pancreatic b-Islet Cells

In insulin-dependent diabetics, the

pancreas has lost its ability to produce
and secrete insulin. These cells can be
injected into the portal vein leading to
the liver. The islets then lodge in the
liver and secrete life sustaining insulin.
Clinical Trials for Liver, Neuronal, and
Cardiovascular Stem Cell Therapy

Other forms of cell therapies that are

still under development include liver
stem cell therapies, neuronal cell
therapies, and cardiovascular cell
therapies, for which many are in
clinical trials and are on the verge of
completion.
Clinical Considerations
What Are Clinically Meaningful
Numbers of Cells?

Currently, the cells required for

clinical practice and experimental cell
therapy protocols fall into the range of
a few tens of millions to a few
billion
What Are the Fundamental Limitations
to the Production of Normal Cells?

The number of divisions a cell

can undergo is dependent on its
maturational lineage stage with key
stages being the (1) stem cells
(diploid,
pluripotent),
(2)
diploid
somatic
cell
subpopulations
(unipotent), and (3) polyploid cell
subpopulations.
How Rapidly Do Normal Cells Grow
in Culture?

Normal cells vary greatly in

their
growth
rates
in
culture.
Hematopoietic progenitors have been
individually clocked at 11- or 12-hr
doubling times, which represents the
minimum cycle time known for adult
human cells.
How These Cells Are Currently
Produced?

Expansion of cells is done in a

variety of culture dishes (T flasks,
roller bottles), in bags (T cells), in
suspension cultures
BIOLOGICAL CONSIDERATIONS
Stem Cells

All tissues consist of a stem cell

compartment that produces cellular
offspring that mature into all tissue
phenotypes.

Which Tissues Have Stem Cells?

For decades it was assumed that
stem cell compartments existed only
in the rapidly proliferating tissues such
as skin, bone marrow, and intestine.
Now, there is increasing evidence that
essentially all tissues have stem cell
compartments, even the central
nervous system
Roles of Stem Cells

The stem cell compartment of a

tissue is the ultimate source of cells
for
turnover
and
regenerative
processes. Stem cell commitment
initiates cell replacement and genesis
of the tissue and, therefore, tissue
repair and maintenance of tissue
functions.
Cellular Communications
How Do Cells Communicate?
1. They secrete soluble signals, known as
cyto- and chemokines.
2. They touch each other and communicate
via direct cellcell contact.
3. They make proteins that alter the
chemical microenvironment (ECM).
Functional Tissue Engineering
Tissue engineering is distinguished
from cell biology by the focus on the
emergent function that arises from the
organization of large numbers of cells into
higher-order structures, variously called
tissues or organs, depending on the level of
anatomical
complexity
and
structural
integration. The re-engineering of complex
human anatomical structures such as limbs
or organ systems is by definition a systems
engineering problem. Though it can be
argued that all tissue functions arise from
fundamental
cellular
mechanisms,
the
system-level organization of tissues and
organs confers function that is not possible
to achieve with individual cells or masses of
unorganized cells in a scaffold. A pile of
bricks does not provide the functionality of a
house, nor does a crate full of car parts
function like an automobile. Analogously,
engineered tissues must be viewed at the
systems level, and the success or failure of
the engineering effort ultimately rests upon a
quantitative assessment of the organ-level
function of the engineered tissue or organ.
Conclusion
Tissue engineering is an effort that is
still in an embryonic stage, but the use of

order of magnitude and dimensional analysis

is proving to be valuable in designing and
reconstituting tissue function. The ability to

engineer tissues will undoubtedly markedly

improve over the coming decades.