Biomedical Engineering Department

Biomaterial Lectures

Biomaterials- MEE 220

Lecture 1
1- Overview
Many materials are subjected to forces or loads when in use. In such situations, it is necessary
to know the characteristics of the material and to design the member in order to avoid failure
during the expected life and service environment of the material. Key mechanical design
properties are stiffness, strength, hardness, ductility, and toughness. Factors to be considered
include the nature of the applied load and its duration, as well as the environmental conditions.
The applied loads could be tensile, compressive, or shear and their magnitudes may be constant
with time or may fluctuate continuously. Application time may be only a fraction of a second, or
it may extend over a period of many years. There are many important factors. In this course, we
will introduce how the various mechanical properties, surface properties are measured and what
these properties represent.in addition to many application and state advanced materials used in
field.

By the end of this lesson, you should be able to:

 mechanical properties, practical tests

 Define stress and strain.
 Define elastic region, plastic region, fracture point, elasticity, tensile strength, and the
yield strength.
 Given a stress-strain diagram, determine elastic region, plastic region, fracture point,
elasticity, tensile strength, and the yield strength.
 Distinguish between tensile, compressive, shear, and torsional stress.
 Define hardness, resilience, and toughness.
 Evaluate whether a material is ductile or brittle using a stress-strain diagram.

 Know what government body regulates medical devices;

 Be able to differentiate between the various classes of medical devices from a regulatory
perspective and be able to provide examples of each class of device;
 Understand what is meant by biocompatibility testing and why it is a necessary consideration in
the manufacture of medical devices;
 Understand what is meant by the phase, “biological response to contact with materials”;
 List the different procedures used to test biocompatibility;
 Be able to broadly differentiate between the different classes of biomaterials;
 Explain what a materials is and how they are used clinically;
 From a biomedical device standpoint, know what is generally required of a biomaterial to be
incorporated within a biomedical device
 Nano-technology
 Surface Properties of Biomaterials , Wound healing response
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 Surface Characterization and treatment

 Examples and description of some materials and their application

2- Course Contents
Topics
Definition of Biomaterial.
Outline about materials used in each field and its requirements.
Outline about various class of biomaterials. Natural and artificial materials.
Characteristics of biomaterials Artificial materials: ceramics ,metals and alloys.
Describe the crystal arid Atomic structures of engineering materials.
Discuss the mechanical tests : Static tension test and fracture in tension. Discuss
the effect of different variables on tensile properties.
Phase diagram ,discuss the mechanical tests :compression test and failure of
materials undercompression. Describe analytical methods used to characterize
biomaterials. Static tests and solved examples. Analysis the loads and factors that
affect on implant.
Describe various aspects of biomedical device design, fabrication and testing.
Analysis the loads and factors that affect on implant.
Introduction to tissue engineering ,preparation and evaluation of tissue
engineering implant. Characteristics of biomaterials surfaces.
Characterization methods of Biomaterials.
Characteristics of biomaterials surfaces.
Characterization methods of Biomaterials. Applications in Dentistry.
Surface & Protein Interactions
Types and application in human body.
Tissue engineering as an application, Adhesives and Composite
Structure.Applications in Drug Delivery.
Project Presentations
Degradation of biomaterials in biological environments.
Project Presentations
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Lecture 2

Introduction

The Biomedical Materials Science course offers you the opportunity to gain a
comprehensive background in the medical science and engineering of the
biomaterials used to repair or replace damaged, diseased or missing tissues in
the human body.

Biomaterials: Materials used to safely replace or interact with

biological systems

A very short history of biomaterials

 The Romans, Chinese, and Aztec used gold in dentistry more than 2000
years ago. Glass eyes and wooden teeth have been used trough much of
the recorded history.
 Synthetic plastics became available at the turn of last century.
 PMMA (Polymethyl methacrylate) was intoduced in dentistry in 1937.
 Experiments with parachute cloth (Vinyon N) as vascular prosthesis after
world war II.
 In the early 1960s total hip replacement made of PMMA, ultrahigh-
molecular-weight polyurethan, and stainless steel.

Important definitions
 Biomaterial — it is a nonviable material used in a (medical) device
intended to interact with biological systems (Williams 1987).
 Biocompatibility — The ability of a material to perform with an
appropriate host response in a specific application (Williams 1987).
 Host Response — The response of the host organism (local and
systemic) to the implanted material or device. As hemodialysis system
serving as an artificial kidney requires materials that must function in
contact with the patients`s blood and exhibit appropriate membrane
permeability and mass transport characteristics.
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Examples of biomaterial applications

Substitute heart valves
Artifical hips
Dental implants
Intraocular lenses

Interdisciplinary interactions are needed

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Different disciplines have to work together, starting from the identification of a need
for a biomaterial through development, manufacture, implantation, and removal from
the patient.

Lecture 3

Biomaterial Types
Artificial biomaterials can be classified into three categories according to
the nature of their interaction with the surrounding environments;

a- bio-inert material : it is nontoxic and biologically inactive (nearly inert), a

fibrous tissue of variable thickness forms;
b- bioactive material : it is nontoxic and biologically active (bioactive), an
interfacial bond forms;
c- biodegradable or bioresorbable material :it is nontoxic and dissolves, the
surrounding tissue replaces it.

Biomaterials generations

There are three different generations seemed to be clearly marked:

First generation of biomaterials When synthetic materials were first used
in biomedical applications, the using requirements were a suitable physical
properties to match those of the replaced tissue with a minimal toxic
response of the host, so biologically inert or nearly inert materials were
used in order to reduce the corrosion and the releasing ions and particles
after implantation to minimise the immune response and foreign body
reaction.

Mechanical properties and toxicity also play a leading role in the selection
of materials for implant manufacture. When inert biomaterials placed
inside the body, it would elicit a foreign fibrous capsule around the
material which isolates it from the surrounding tissue.

Examples for the first generation biomaterials:

Metals (stainless steel and cobalt–chrome-based alloys, Ti and Ti alloys).
Ceramics (Alumina Al2O3 and Zirconia ZrO2).
Polymers (silicone rubber, acrylic resins).
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The second generation of biomaterials used bioactive materials ‘ability to

interact with the biological environment to enhance the biological
response and the tissue/surface bonding’, and resorbable biomaterials
that have ability to degradation while new tissue regenerates and heals.
Examples for the second generation biomaterials:
Metals (None of the biometallic materials are bioactive; However, two
approaches can be considered to obtain bioactive metals. The first one
consists of coating the surface of the metal with a bioactive ceramic. The
second one is to chemically modify the surface of the metal so as to induce
proteins and cell adhesion and other tissue/material interactions.
Ceramics (Bioactive glass, glass–ceramics and calcium phosphates (CaPs)).
Polymers (Biodegradable polymers of synthetic and natural origin such as
polyglycolide (PGA), polylactide (PLA).

The third-generation biomaterials used bioactive and bioresorbable

materials as temporary three-dimensional porous structures which are able
to activate genes that stimulate regeneration of living tissue. For these
biomaterials, the bioactivity and biodegradability concepts are combined,
so the combination of bioactivity and biodegradability is the most
characteristics of the third-generation biomaterials.
Metals have been used in the development of porous structures that
focused on titanium and titanium alloys.

Summary:

Classification of Materials

1. Metals - one or more metallic element, sometimes non-metallic

elements (C, N, O) in small amounts - good electrical conductivity, good
thermal conductivity; ductile,

2. Ceramics - oxides, nitrides, carbides; good insulators; brittle; refractory

(good thermal resistance) eg. Alumina (Al2O3), silica (SiO2), magnesia
(MgO),
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3. Semi-conductors – intermediate between conductor and insulator; very

important in electronics; important in catalysis; eg. Silicon (Si),
Germanium (Ge), Titania TiO2

4. Polymers - organic macromolecules (plastics, rubber, )

5. Composites - consists of two or more structural materials; trade off in

properties; eg. reinforcement of matrix

6. Advanced Materials: Nanoengineered materials - Mechanical, electronic, magnetic,

catalytic and other properties designed from the molecular level in a “bottom-up” approach as
opposed to a top down approach
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Lecture 4

Properties of materials
Bulk properties, Suface properties, Synthetic materials have specific bulk
and surface characteristics. They must be known prior to any medical
application.in addition to the change over time in vivo must be evaluated
within the context of the intended biomedical use, since applications and
host tissue responses are quite specific within areas (e.g. Cardiovascular:
flowing blood contact; orthopedic: functional load bearing)

Properties and structure

Structure can be viewed at many levels:

–Atomic or molecular –Ultrastructural –Microstructural

Each level of structure in a material affects the overall properties of that

material in different, and sometimes conflicting, ways

Bulk properties of materials

Solids are held together by strong interatomic forces.

Metallic bonding -Covalent bonding -Ionic bonding

Metals and Metallic Bonding

A simple model from classical physics ignoring quantum

mechanical behaviour
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• valence electrons are not bound by a single atom, but are

delocalized and may be considered to form “a sea of
electrons”
• valence electrons are free to flow about the crystal lattice
which consists of stationary ion cores (atomic nuclei and non
valence electrons)
• Free electrons shield ion cores from repulsive forces
• Valence electrons are loosely bound
• High thermal conductivity (k)
• high electrical conductivity ()
• Metallic lattice is less stable than ionic solids
• low melting points (relative to ceramics)

Ceramics and Ionic Bonding

 Ions are created by the electron transfer from Na to Cl due to

large difference in electronegativities
 Ions are more stable, since outer shells become filled (Assignment
One – problem 3c)
 Unlike metals, the electrons are tightly bound by the ions
 Low electrical and thermal conductivities
 Very strong lattice energy results in very high melting points
(eg. Al2O3 Tmp=2020°C)
 Materials with very high temperature resistance are said to be
refractory.
 Ceramics have good insulative properties, thermal stability, are
usually hard and are strong
 Ceramics are also brittle and subject to fracture

Classification by Morphology:
Solids may be classified according to the inherent degree of
molecular order or disorder

1. Crystalline – most highly structured and ordered of all solids

- periodicy; unit cell is repeated in all dimensions of crystal
2. Amorphous - molecular structure is completely random and disordered
(Eg. glass) - the unit cell may be considered to
be infinite in size
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3. Semi-crystalline - Eg. Polymers; crystallinity is localized within

amorphous structure
4. Liquid Crystal Polymers – eg. Liquid crystal display

- do not fall into first three categories;

- a structurally unique and novel state of matter neither liquid nor

crystal in melt condition

- complex; extended rod shaped, rigid molecules

Conclusion:

Performance depends on material properties

• Macroscopic material properties are governed by the microstructure

• The microstructure is determined by crystal structure
• Crystal structure is determined by atomic bonding
• Classification of solids by atomic bonding and elemental constituents
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Lecture 5

Material Properties

• OBJECTIVES
• To introduce the fundamental mechanical and surface chemistry
properties of biomaterials
• OUTLINE
– Mechanical Properties
• elasticity, viscoelasticity, brittle fracture, fatigue

- Surface chemistry

Introduction to mechanical properties

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Let us take a cylinder and stress it. To stress it, I would fix one end of the cylinder and pull from
the other end as shown in the figure below.

Tensile Stress
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According to Newton's third law, the cylinder will experience a force downward on the lower
surface of the cylinder and an equal and opposite force on the upper surface of the
cylinder. cylinder has an original length of I o and surface area of Ao. As I pull on
my material with the force F the cylinder will lengthen and the resulting length will
be l. Stress, σ, is defined as the force divided by the initial surface area,
σ=F/Ao. This pulling stress is called tensile stress. Strain is what results from this
stress. Strain, ε, is defined as the change in length divided by the original
length, ε=ΔI/Io. Before we proceed further with stress and strain, let's define some
other types of stress. 

If instead of pulling on our material, we push or compress our cylinder we are

introducing compressive stress. This is illustrated in the following figure:

if instead of applying a force perpendicular to the surface, we apply parallel but

opposite forces on the two surfaces we are applying a shear stress. This is
illustrated in the following figure:
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Shear Stress

Stress related to shear is torsional stress. If we hold one end of our cylinder fixed
and twist the other end as shown in the figure below, we are applying a torsional
(or twisting) stress.

Torsional Stress

Elastic Region
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It is the region where the material can be deformed and when released will return
back to its original configuration. Many metals in the elastic region have a
resulting strain that is proportional to the tensile load when the applied tensile load
is small. Mathematically, this can be written as ε=Eσ , and more generally is
known as a form of Hooke's law. E is the proportionality constant and is called the
modulus of elasticity or Young's modulus. Physically, the larger the value of the
modulus of elasticity the stiffer the material is, i.e., the more resistant to bending
the material is. If we look at a stress-strain diagram for a metal in the elastic region
such as that shown in the figure below, the slope of the curve is the modulus of
elasticity.

Stress-Strain Diagram

Plastic Deformation
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For most metallic materials, the elastic deformation region is relatively small. At
some point, the strain is no longer proportional to the applied stress. At this point,
bonds with original atom neighbors start to break and reform with a new group of
atoms. When this occurs and the stress is relieved, the material will no longer
return to its original form, i.e., the deformation is permanent and nonrecoverable.
The material has now moved into the region referred to as plastic deformation. In
practice, it is difficult to identify the exact point at which a material moves from
the elastic region to the plastic region. As shown in the figure below, a parallel line
offset by 0.002 strain is drawn. Where that line intercepts the stress-strain curve is
identified as the yield strength. The yield strength is equal to the stress at which
noticeable plastic deformation has occurred.

Stress-strain curve.

For many materials, the stress-strain curve looks like the curve shown in the figure
below. As the stress is increased from zero, the strain increases linearly until it
starts to deviate from linear at the yield strength. For increasing stress, the curve
proceeds to a maximum at which point it curves downward toward the fracture
point. The maximum corresponds to the tensile strength, which is the maximum
stress value for the curve and is indicated by M in the figure. The fracture point is
the point at which the material ultimately breaks, indicated by F in the figure.
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Maximum on stress-strain curve appears at the onset of noticeable necking.

Resiliency and Toughness

When a person is resilient, we mean that they bounce back from change to their
original personality. Resiliency in the material sense is similar. We can define
resilience of the material to be the amount of energy the material can absorb and
still return to its original state. If we are talking about stressing the material and
having it return to its original state, we are talking about the material remaining in
the elastic region of the stress-strain curve. It turns out that we can get the energy
of elasticity by taking the area under the curve of the stress-strain curve. That area
has been highlighted in the figure below, which is the area under the curve from
the origin to the yield strength.
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Energy of elasticity shown under the curve of the stress-strain curve. 

Credit: Callister

Toughness, in contrast to resilience, is how much energy can be absorbed and still
keep going. One analogy that can be used when describing toughness is that of a
car in a demolition derby. The car is allowed to continue the competition as long as
it is capable of moving. It does not matter how many hits and how much
destruction has been done to the car, but rather as long as the car can move it can
stay in the competition. The toughness of the car is based on how many hits and
how much damage the car can sustain and continue in the competition. In the case
of materials, the amount of energy that the material can absorb plastically before
fracturing is the toughness.
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In the figure below, we can see that a material can have a high tensile strength
(ceramics) and yet have a small toughness. In addition, materials can be extremely
ductile (unreinforced polymers) and also have a small toughness. So, a large
toughness (metals) is obtained by having a high tensile strength and a high
ductility.

Stress-strain curve for a material with a high tensile strength (ceramics) and a small
toughness.

What is a Brittle Material?

Brittle material breaks while little to no energy is absorbed when stressed. The
material fractures with no plastic deformation. The material in the figure below
marked with (a) shows what a brittle material will look like after pulling on a
cylinder of that material. Typically, there will be a large audible snap sound when
the brittle material breaks. A brittle material is also known as a material having low
ductility. A stress-strain curve for brittle and ductile materials is shown in the
figure below.
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Stress-strain curve for brittle and ductile materials.

why are ceramics so much more brittle than metals? It has to do with the bonding.
In metals, their metallic bonds allow the atoms to slide past each other easily. In
ceramics, due to their ionic bonds

Malleability and Ductility

Malleability and ductility are related. A malleable material is one in which a thin
sheet can be easily formed by hammering or rolling. In other words, the material
has the ability to deform under compressive stress.
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A malleable material is one in which a thin sheet can be easily formed by

hammering. Gold is the most malleable metal.

In contrast, ductility is the ability of a solid material to deform under tensile stress.
Practically, a ductile material is a material that can easily be stretched into a wire
when pulled as shown in the figure below. Recall pulling is applying tensile stress.

Ductility test.

If we pull on a rod of material, some of the possible profiles of the rods at fracture
are shown in the figure below.
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Fracture Samples

Profile (a) is an example of the material that fractures with no plastic deformation,
i.e., it is a brittle material. Profile (b) is an example of a material that fractures after
very little plastic deformation. These two profiles would be classified as having
low ductility. Profile (c) in contrast is a material that plastically deforms before
fracture. This material has high ductility. The stress-strain curves for the brittle,
profile (a), and the ductile material, profile (c), are shown in the figure below.
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Ductile and Brittle Stress-Strain Curves

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Lecture 6

Surface Energy

• Interface
– boundary between 2 layers

protein adsorption to materials

blood coagulation/thrombosis due to material contact

cellular response to materials

• At the surface (interface) there are intermolecular forces and intramolecular

forces of attraction and repulsion.

Surface Electrical Properties

• surface may become charged by

– adsorption of ionic species present in sol’n or preferential adsorption
of OH-
– ionization of -COOH or -NH2 group
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Electric Double Layer

• it is a structure that appears on the surface of an object when it is placed into

a liquid.
• The DL refers to two parallel layers of charge surrounding the object.
• The first layer, the surface charge comprises ions adsorbed directly onto the
object due to chemical interactions.
• The second layer is composed of ions attracted to the surface charge via the
coulomb force, electrically screening the first layer.
• This second layer is loosely associated with the object, because it is made of
free ions which move in the fluid under the influence of electric attraction
and thermal motion .

Surface Energy and the Contact Angle

LV


SV SL
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We denote the solid–vapor energy as , the solid–liquid interfacial energy as and the liquid–vapor
energy (i.e. the surface tension) as simply , we can write an equation that must be satisfied in
equilibrium (known as the Young Equation):
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The contact angle can also be used to determine an interfacial energy (if other
interfacial energies are known). This equation can be rewritten as the Young-
Dupre equation:

where W is the adhesion energy per unit area of the solid

Critical Surface Tension, gc

The critical surface tension is the surface tension of a liquid that would
completely wet the solid of interest.
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Lecture 7: Revision sheet and solved problems

Lecture 8: Mid Term Exam
Lecture 9
Surface Modification for Biomaterials Applications

The cellular response to the material should be evaluated by performing in vitro

and in vivo experiments.–Cell adhesion–Cell motility–Protein or enzyme
production–Gene expression–Cell death or toxicity
- Surface Modification Techniques
-Biological Surface Modification Techniques
-Surface Patterning Techniques
a-- Protein Adsorption
Factors affecting adsorption:
• Surface energy
• Surface hydrophobicity
• Surface charge
• Important Definitions:
• Hydrophobic: water fearing
• Hydrophilic: water loving
• Adsorption: adhesion to solid surface
• Absorption: penetration of molecules into bulk
Surface Tension
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 Adding molecules that prevent adsorption is called steric

hindrance.
for example : polyethylene glycol (PEG) attaches to the surface
(hydrophobic) preventing protein adhesion
 Surface modification with no overcoat, and laser methods for
surface modification make surface locally attractive for adhesion
of desired species
Methods of surface coating: Plasma Discharge

Charged particles are attracted to the sample surface, which acts as the
cathode. Particles may be positive or negative ions, free radicals,
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electrons, atoms, molecules or photons. Often used to add OH or NH 2

groups to surface as a precursor to further modification
Plasma Discharge
• Advantages:
– Coatings are conformal
– Free of voids/pinhole defects
– Easily prepared
– Sterile when removed from reactor
– Produce low amount of leachable substances
– Demonstrate good adhesion to substrate
– Allow unique film chemistries to be produced
– Easily characterized
• Disadvantages
– Chemistry within reactor may be undefined
– Equipment often expensive
– Uniform reaction within long, narrow pores may be difficult
– Care must be taken in sample preparation to prevent
contamination
Vapor Deposition: Physical (PVD)
Physical Vapor Deposition (PVD) may be from evaporation or
sputtering. Sometimes a plasma is used to create high energy species
that collide with target .
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Vapor Deposition: Chemical (CVD)

In Chemical Vapor Deposition (CVD) a reactive gas is passed over the
substrate to be coated, inside of a heated, environmentally controlled
reaction chamber. In this case , CH 4 gas is introduced to create a
diamond-like coating.
Physiochemical coatings
Physiochemical coatings are used to coat biomaterials with biologically
active molecules. These methods include solution coatings and
Langmuir-Blodgett films.
Coatings are amphiphilic, having a hydrophilic head and hydrophobic
tail. This causes the heads to remain in the water and the tails to extend
above the surface. The molecules at the head may be tailored to enable
crosslinking with other molecules or to the biomaterials surface

Study more modification methods from refrance

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Lecture 10, 11
Nanotechnology
What is Nanotechnology?

• Lycurgus cup,4th century AD (now at the British Museum, London).

• Depicts King Lycurgus of Thrace being dragged to the underworld
• When illuminated from outside, it appears green. However, when
illuminated from within the cup, it glows red.
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Size-Dependent Properties
If you cut a block of gold into smaller & smaller pieces, it would still look
like gold. Not true of gold at the nanoscale, where properties change.

Optical Properties of Gold

Bulk gold appears yellow in color while, Nanosized gold appears red in
color
 The particles are so small that electrons are not free to move about as
in bulk gold (the energy gap between conduction and valence bands
increases with decreasing size)
 Because this movement is restricted, the particles react differently
with light
Optical Properties of Zinc Oxide (ZnO)
 Large ZnO particles
- Block UV light
- Scatter visible light
- Appear white
 Nanosized ZnO particles
- Block UV light
- So small compared to the wavelength of visible light that they
don’t scatter it
- Appear clear
Optical Properties - TiO2 and ZnO
• Scattering of visible light (whitening effect) is influenced by particle size
and the difference between the refractive index of the pigment and the
surrounding media.
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• Maximum scattering occurs when size equals 1/2 the wavelength and
particles are uniformly dispersed (Mie theory).
Mention method of preparation nano-particles

For Lycurgus cup, The colors originates from metal nanoparticles

embedded in the glass. At places, where light is transmitted through the
glass it appears red, at places where light is scattered near the surface,
the scattered light appears greenish.
This is due to: Suspensions of spherical gold particles with various
diameters (150, 100, 80, 60, 40, 20 nm) in water. The difference in colors
is due to different scattering and absorption behaviour of small and
large gold particles.
• Gold nanoparticle can be suspended in water to make a colloidal gold,
used for centuries as a medical treatment . [ ‫مصطفى السيد‬.‫]د‬
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Lecture 11
Physical Properties of nanoparticles
Physical Properties Change: Melting Point of a Substance
Melting Point (Microscopic Definition)
 Temperature at which the atoms, ions, or molecules in a substance
have enough energy to overcome the intermolecular forces that
hold them in a “fixed” position in a solid
 Surface atoms require less energy to move because they are in
contact with fewer atoms of the substance

Melting Point of Small Objects

- The smaller a solid object gets, the larger the percentage of its
atoms residing at the surface. If it keeps shrinking, eventually
it's practically all surface.
- Inside a crystalline solid the atoms are constrained by the
crystal lattice, but at the surface the atoms have more freedom
to move.
- As the temperature increases, they begin to vibrate; when the
vibration of the surface atoms reaches a certain percentage of
the bond length between them, melting begins and then starts to
propagate through the solid
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At the macroscale At the nanoscale

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The majority …almost all on the …split between the

of the atoms inside of the object inside and the surface
are… of the object

Changing an …has a very small …has a big effect on

object’s effect on the the percentage of
size… percentage of atoms atoms on the surface
on the surface
The melting …doesn’t depend on … is lower for smaller
point… size particles
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Surface to Volume Ratio Increases

• As surface to volume ratio increases
- A greater amount of a substance comes in contact with surrounding material
- This results in better catalysts, since a greater proportion of
the material exposed
for reaction
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• Mixing two or more chemically dissimilar materials------Composites

• The goal is to achieve properties that are otherwise unreachable in individual
components
• Some advantages: High strength/light weight, low cost, environmentally
resistant, electrically and thermally conductive
• Natural Composites:
• Wood: mixture of flexible cellulose fibers and stiffer lignin
• Bone: mixture of soft collegen (protein) and brittle apatite (mineral)
• Combine strong, stiff, or electrically or thermally conductive, or
magnetic particles/fibers/layers with adhesive, soft, relatively ductile
plastics. -----polymer+ composite
• Nano-Products in medicine
• FeO nanoparticles injected into tumor site.
• Alternating magnetic field (similar to MRI) heats up nanoparticles,
destroying tumor from inside with minimal damage to surrounding tissue
• Nanosensor
• Particles that are smaller than the characteristic lengths associated with the
specific phenomena often display new chemistry and new physics that lead
to new properties that depend on size
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• When the size of the structure is decreased, surface to volume ratio increases
considerably and the surface phenomena predominate over the chemistry
and physics in the bulk
• The reduction in the size of the sensing part and/or the transducer in a sensor
is important in order to better miniaturise the devices
• Science of nano materials deals with new phenomena, and new sensor
devices are being built that take advantage of these phenomena
• Sensitivity can increase due to better conduction properties, the limits of
detection can be lower, very small quantities of samples can be analysed,
direct detection is possible without using labels, and some reagents can be
eliminated.
• A nanosensor probe carrying a laser beam (blue) penetrates a living cell to
detect the presence of a product indicating that the cell has been exposed to a
cancer-causing substance

Next lecture : tissue engineering

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Lecture 12
Tissue Engineering

Tissue engineering

Tissue engineering is a field whereby damaged or missing tissue is replaced or facilitated

in its regeneration.

Tissue engineering is based on isolating cells

from an individual and expanding them in
culture. These cells are then seeded on a
biocompatible, porous and biodegradable
carrier, called “scaffold”, where they start to
proliferate and secrete their extracellular matrix.

Properties of Ideal /Scaffolds characteristics

The following characteristics must be considered when designing a scaffold for tissue
engineering.
a. Biocompatibility

Biocompatibility is the ability of the scaffold to perform in a specific application without eliciting a
harmful immune or inflammatory reaction. For a scaffold to positively interact with cells and with
minimal disruption to the surrounding tissue, it should have an appropriate surface chemistry to allow for
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cellular attachment, differentiation and proliferation.[ surface roughness ]Cells primarily interact with
scaffolds via chemical groups on the material surface or topographical features.

b. Biodegradability

Biodegradation is the dissolution of the scaffold by the cellular and enzymatic reactions. This
occur when the scaffold is exposed to a biological environment, either in vivo or in vitro, a
different mechanisms may be involved in either setting.
In vivo, scaffolds are degraded during the foreign body response against the scaffold, a process
which may involve an immune response, release of enzymes, and deposition of replacement
extra-cellular matrix. Understanding the foreign body response to a given biomaterial is a key
step in developing a clinical therapy . In vitro, scaffold degradation is dependent upon the cell
type and medium content.
Degradation products should be non-toxic. If there is toxic products , it should have a
degradation rate slow enough for the body to manage .

c. Mechanical Properties

The scaffold provides structural integrity in 3D. It, also provides mechanical stability to support the
growing tissue during in vitro and/or in vivo growth phases . This mechanical stability is required to meet
the specific requirements of the tissue to be regenerated at the defect site. These requirements allow for
handling by the clinician, are able to withstand the mechanical forces imposed on it during the
implantation procedure and survive under physiological conditions. After implantation, the scaffold has a
minimal level of biomechanical function improve mechanically until normal tissue function is restored
and fully integrated with the surrounding host tissue.

d. Scaffold Architecture

Scaffold with Porous structures allow for optimal interaction with cells. The scaffold pore architecture
is characterised by pore size and shape, pore interconnectivity, degree of porosity and surface area. These
characteristics determine cell interactions with the scaffold. It leads to a molecular transport (movement
of nutrients, wastes and biological chemicals e.g. growth factors) within the scaffold. Scaffold pore size
determines the cell seeding efficiency [50]. Very small pores prevent the cells from penetrating the
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scaffold. Very large pores prevent cell attachment due to a reduced area. Cell migration within a scaffold
is determined by degree of porosity and pore interconnectivity.

A scaffold with an open and interconnected pore network (>80 %), and a high degree of porosity is ideal
for the scaffold to interact and integrate with the host tissue . But, with increasing porosity, mechanical
properties decrease. In manufacturing scaffold, a compromise between different properties according to
application requirements is required.

Zeta potential [mV] Stability behaviour of the colloid

from 0 to ±5, Rapid coagulation or flocculation
from ±10 to ±30 Incipient instability
from ±30 to ±40 Moderate stability
from ±40 to ±60 Good stability
more than ±61 Excellent stability

Process Advantage Disadvantage

Thermally High porosities (_95%) Long time to sublime solvent (48
induced phase Highly interconnected pore structures hours) Shrinkage issues
separation Anisotropic and tubular pores possible Small scale production
(TIPS) Control of structure and pore size by Use of organic solvents
varying preparation conditions Limited range of pore size

Solvent and Controlled porosity Controlled Structures are isotropic

particle leaching interconnectivity (if particles are Use of organic solvents
sintered) Poor interconnectivity
control of porosity structure Limited membrane thickness(3mm)

Solid free-form Porous structure can be tailored to host Resolution needs to be improved to
tissue the micro-scale
Protein and cell encapsulation possible Some methods use organic solvents
Good interface with medical imaging
Polymeric Graded porosity structures possible Mechanical properties is an issue
Sponge method Controlled pore size
High porosity
High interconnection
Emulsion Independent control of porosity and pore Problem with residual solvent,
templeting size Residual progens
Superior compressive strength Less than 200μm
Foaming-pressure No organic solvents Non-porous external surface or
processing High interconnection Closed pore structure may be
produced
Electro-spinning use of solvents that may be toxic
need high voltage
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The need for TE

Required for application requirements

Scaffold Cell

Biomaterial as raw material

Ceramics% Polymer % Composite %

Scaffold processing

Combination Emulsion Leaching Foaming Phase separation Electospinning Proto-type

Scaffold evaluation

Imaging methods Traditional methods

U. S. SEM U-CT Mercury Porosimetry

InfraRed Spectroscopy

Lecture 13, 14: Revision, Quizz, Report presentation for each group
Thanks and Good Luck
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