MSE 536: Introduction to Advanced
Biomaterials
Fall, 2010
Dr. R. D. Conner
MSE-536
A biomaterial is “a material intended to interface
with biological systems to evaluate, treat, augment
or replace any tissue, organ or function of the
body”
Biocompatibility — The ability of a material to
perform with an appropriate host response in a
specific application
Host Response — The response of the host
organism (local and systemic) to the implanted
material or device.
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Examples of Biomaterials in the News
1.
2.
3.
4.
5.
Marrow stem cells could heal broken bones,
Betterhumans
Newly grown kidneys can sustain life in rats,
Bio.com
Doctors grow new jaw in man's back, CNN
FDA approves implanted lens for
nearsightedness, CNN
Stent recall may raise quality expectations,
Medical Device Link
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The REPIPHYSIS® works by inserting an
expandable implant made from titanium in an
aerospace polymer into the child’s healthy
bone, after which standard recovery and
rehabilitation are expected. However, instead
of undergoing repeated surgeries to extend
the bone, the REPIPHYSIS® uses an
electromagnetic field to slowly lengthen the
implant internally.
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A brief history of biomaterials
•Romans, Chinese, and Aztecs used gold in dentistry over 2000 years ago,
Cu not good.
•Eyeglasses
•Ivory & wood teeth
•Aseptic surgery 1860 (Lister)
•Bone plates 1900, joints 1930
•Turn of the century, synthetic plastics came into use
•WWII, shards of PMMA unintentionally got lodged into eyes of aviators;
Parachute cloth used for vascular prosthesis
•1960- Polyethylene and stainless steel being used for hip implants
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Biomaterials for Tissue
Replacements
• Bioresorbable
vascular graft
• Biodegradable nerve
guidance channel
• Skin Grafts
• Bone Replacements
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A few examples…
Contact Lens
composite foam seeded
with bone marrrow
stromal cells
Bileaflet heart valve
prosthesis
Problems with heart valves:
•Mechanical failure
•Blood clotting
•Tissue overgrowth
Image of blood clots on a bileaflet heart
valve
Image of vascular grafts constructed of
expanded poly-tetrafluoroethylene (Teflon)
An orthopedic hip implant,
exhibiting the use of all three
classes of biomaterials: metals,
ceramics and polymers. In this
case, the stem, which is
implanted in the femur, is made
with a metallic biomaterial. The
implant may be coated with a
ceramic to improve attachment to
the bone, or a polymeric cement.
At the top of the hip stem is a ball
(metal or ceramic) that works in
conjunction with the
corresponding socket to facilitate
motion in the joint. The
corresponding inner socket is
made ot of either a polymer (for a
metallic ball) or ceramic (for a
ceramic ball) and attached to the
pelvis by a metallic socket.
Schematic of a heartlung machine setup.
Potential Problems:
•High resistance in filter leads to high blood
pressure
•Low oxygenation efficiency
•Anticoagulants necessary to prevent clotting
Advanced and Future Biomaterials
• Cell matrices for 3-D growth and tissue
reconstruction
• Biosensors, Biomimetic , and smart devices
• Controlled Drug Delivery/ Targeted delivery
• Biohybrid organs and Cell immunoisolation
– New biomaterials - bioactive, biodegradable,
inorganic
– New processing techniques
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Evolution of Biomaterials
Structural
Soft Tissue
Replacements
Functional Tissue
Engineering Constructs
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Biological Responses to
Biomaterials
• Biocompatibility:
Incompatibility leads to:
Other reactions include:
inflammation
redness
Protein
swelling
and
warmth
cellular
pain
response
immune system
determine
activation
success of
blood clotting
an implant
infection
tumor formation
implant calcification
The road to FDA approval
Approval Steps:
1. In vitro testing (“in glass”)
2. In vivo testing w/healthy
animals
3. In vivo testing w/animal
models of disease
4. Controlled clinical trials
Biomaterials is a $9 Billion
business in the U.S.
•Over 100,000 Heart
Valves
•300,000 Vascular grafts
•500,000 Artificial Joints
Skin/cartilage
Drug Delivery
Devices
Polymers
Bone
replacements
Orthopedic
screws/fixation
Metals
Ocular
implants
Synthetic
BIOMATERIAL
S
Ceramics
Dental
Implants
Heart
valves
Dental Implants
Implantable
Microelectrode
Semiconductor
Materials
Biosensors
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Common Applications for Materials
Ceramics
Metals
Polymers
Polymers
• Polymers fall into three categories:
– Elastomers (e.g. rubber bands)
– Composites
– Hydrogels (absorb/retain H2O)
• Polymers may be natural or synthetic
– Natural polymers are derived from sources
within the body: collegen, fibrin, hyaluronic
acid (from carbohydrates), or outside:
chitostan (from spider exoskeletons) or
alginate (from seaweed)
– Chitostan & alginate are used as wound
dressings
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Polymers: many repeating parts
Chemical structure of poly (methyl
methacrylate), a polymer commonly used as a
bone cement. (a) shows a section of the
polymer chain, with the dotted lines indicating
the repeating unit, which is also shown in (b)
Advantages & Disadvantages
of Natural Polymers
Advantages:
Chemical composition similar to material they are
replacing: easily integrated into host and modifiable
Disadvantages:
•Difficult to find in quantity
•Low mechanical properties
•Non-assurance of pathogen removal
•May be recognized as foreign by immune system
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Advantages & Disadvantages
of Synthetic Polymers
Advantages:
•Easily mass produced and sterilized
•Can tailor physical, chemical, mechanical and
degradative properties
Disadvantages:
•Do not interact with tissue in an active manner,
thus cannot direct or aid in healing around implant
site
•Few have been approved by FDA
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Biomaterial Processing
Techniques developed to change surface
chemistry while leaving bulk material
unchanged; e.g.:
•ceramic coatings on hips,
•coating a catheter with antibiotics
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Important Properties
Interaction between material & host
•Degradative: affected by the shape, size, and bulk
chemical, physical and mechanical properties
•Corrosion: pH
•Surface properties: biological response affected by
proteins adsorbed to surface. Surface chemistry
affects adsorption
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Important Biomaterial Property: Wetting
Wetting is a measure of a fluid’s ability to
spread out on a solid substrate
Hydrophobicity is a measure of a materials
attraction to water. If it is hydrophobic it is
“water fearing” and does not wet; if it is
hydrophilic it is attracted to water and spreads
The Chemistry of Materials
The Bohr atomic model, which separates the atom
into a nucleus (containing protons and neutrons)
and orbiting electrons. For an electrically neutral
atom, the positive charge of the nucleus is
balanced by an equal number of electrons. In this
model, electrons are depicted as orbiting the
nucleus in discrete energy states, or orbitals,
which are separated by a finite amount of energy.
The energy an electron looses by
moving from an outer to an inner shell
is released as a photon, with
energy E = hn
The distribution of the
hydrogen electron as
depicted by both the (a)
Bohr and (b) the wavemechanical models.
However, in the wavemechanical model,
orbitals are thought of as
the probability that an
electron will occupy a
certain space around the
nucleus and they are
characterized by
probability functions.
Depiction of the energy states for the 2p subshell.
Because each subshell has a characteristic shape
as determined by the electron probability functions
(dumbbell-shaped for p subshells), the different
energy states are represented by identical
subshells oriented along different axes (x, y and z)
The relative energies of shells and subshells for all
elements. Note that the lower the shell number, the
lower the energy (e.g., energy associated with 1s is less
than for 2s). Additionally, the energy of the subshells in
each shell increases from s to f. However, energy
states can overlap between shells (e.g., energy of the
3d shell is greater than the 4s).
Order of filling
electron orbitals
The Periodic Table of
Elements
Atomic bonding
Ft = Fa + Fr
U = ∫Ft dr
Tm = depth of well
E = d2U/dr2
a is proportional to the
asymmetry in the
potential well
PROPERTIES FROM BONDING: TM
• Bond length, r
F
• Melting Temperature, Tm
F
r
• Bond energy, Eo
Tm is larger if Eo is larger.
PROPERTIES FROM BONDING: E
• Elastic modulus, E
Elastic modulus
F
L
=E
Ao
Lo
• E ~ curvature at ro
Energy
unstretched length
ro
r
E is larger if Eo is larger.
smaller Elastic Modulus
larger Elastic Modulus
PROPERTIES FROM BONDING: a
• Coefficient of thermal expansion, a
coeff. thermal expansion
L
= a(T2-T1)
Lo
• a ~ symmetry at ro
a is larger if Eo is smaller.
•
•
•
•
IONIC BONDING
Occurs between + and - ions.
Requires electron transfer.
Large difference in electronegativity required.
Example: NaCl
EXAMPLES: IONIC BONDING
• Predominant bonding in Ceramics
NaCl
MgO
CaF2
CsCl
H
2.1
Li
1.0
Be
1.5
Na
0.9
Mg
1.2
K
0.8
Rb
0.8
Ca
1.0
Sr
1.0
Cs
0.7
Ba
0.9
Fr
0.7
Ra
0.9
Ti
1.5
Cr
1.6
Give up electrons
Fe
1.8
Ni
1.8
He
-
Zn
1.8
As
2.0
O
F
3.5 4.0
Cl
3.0
Ne
-
Br
2.8
I
2.5
Kr
Xe
Rn
-
At
2.2
Acquire electrons
Ar
-
COVALENT BONDING
• Requires shared electrons
• Example: CH4
C: has 4 valence e,
needs 4 more
H: has 1 valence e,
needs 1 more
Electronegativities
are comparable.
EXAMPLES: COVALENT BONDING
H2
H
2.1
Li
1.0
Na
0.9
K
0.8
Be
1.5
Mg
1.2
Ca
1.0
Rb
0.8
Cs
0.7
Sr
1.0
Fr
0.7
Ra
0.9
•
•
•
•
Ba
0.9
column IVA
H2O
C(diamond)
SiC
Ti
1.5
Cr
1.6
Fe
1.8
Ni
1.8
Zn
1.8
Ga
1.6
C
2.5
Si
1.8
Ge
1.8
F2
He
O
2.0
As
2.0
Sn
1.8
Pb
1.8
GaAs
Molecules with nonmetals
Molecules with metals and nonmetals
Elemental solids (RHS of Periodic Table)
Compound solids (about column IVA)
F
4.0
Ne
-
Cl
3.0
Ar
Kr
-
Br
2.8
I
2.5
At
2.2
Xe
-
Rn
-
Cl2
Formation of four sp3
hybrid orbitals from one
valence electron in the
2s and three in the 2p.
Each of the newly formed
hybrid orbitals have a
large lobe that can be
directed toward other
atoms to promote
covalent binding.
Spatial orientations of the most
common hybrid orbital types. The
spatial orientation of the hybrid
orbitals affects where bonding
occurs and results in different bond
angles for different compounds.
There are two types of bonds: s and p. s
bonds occur along the participating orbitals
axis; p occur at right angles to the
participating orbitals
Bonds can also be “bonding” or “antibonding”
When forming molecular orbitals.
antibonding molecular orbitals have higher
Energy than bonding orbitals
(a) s molecular orbitals. s bonding
and antibonding molecular orbitals
describe the electron density in the
line between two nuclei. (b-c) p
molecular orbitals. p bonding and
antibonding molecular orbitals
arise from the sideways overlap of
atomic orbitals and therefore
describe the electron density in
spatial orientations other than that
along the internuclear axis.
(a) Hydrogen bond between water molecules. The electronegative oxygen draws
electrons away from the hydrogen nucleus, which, in combination with the extra,
unbonded electrons in the oxygen atom, causes the oxygen portion of the molecule to
carry a partial negative charge. The hydrogen atoms can then interact with the
negative (oxygen) end of another water molecule to form the hydrogen bond. (b) An
illustration of a three-dimensional lattice of hydrogen bonds in water.
METALLIC BONDING
• Arises from a sea of donated valence electrons
(1, 2, or 3 from each atom).
Schematic of metallic bonding.
Because there are no
electronegative elements to
accept the valence electrons, the
electrons are donated to the
entire structure. This creates a
“cloud” or “sea” of electrons that
are mobile and surround a core of
cations.
• Primary bond for metals and their alloys
SECONDARY BONDING
Arises from interaction between dipoles
• Fluctuating dipoles
• Permanent dipoles-molecule induced
-general case:
-ex: liquid HCl
-ex: polymer
SUMMARY: PRIMARY BONDS
Ceramics
(Ionic & covalent bonding):
Metals
(Metallic bonding):
Polymers
(Covalent & Secondary):
Large bond energy
large Tm
large E
small a
Variable bond energy
moderate Tm
moderate E
moderate a
Directional Properties
Secondary bonding dominates
small T
small E
large a
METALLIC CRYSTALS
• tend to be densely packed.
• have several reasons for dense packing:
-Typically, only one element is present, so all atomic
radii are the same.
-Metallic bonding is not directional.
-Nearest neighbor distances tend to be small in
order to lower bond energy.
• have the simplest crystal structures. 74 elements
have the simplest crystal structures – BCC, FCC
and HCP
We will look at three such structures...
3
The crystal lattice
A point lattice is made up of regular,
repeating points in space. An atom or
group of atoms are tied to each lattice
point
14 different point lattices, called Bravais lattices, make up the crystal system.
The lengths of the sides, a, b, and c, and the angles between them can vary for
a particular unit cell.
Three simple lattices that describe metals are Face Centered Cubic (FCC)
Body Centered Cubic (BCC) and Hexagonal Close Packed (HCP)
SIMPLE CUBIC STRUCTURE (SC)
• Rare due to poor packing (only Po has this structure)
• Close-packed directions are cube edges.
• Coordination # = 6
(# nearest neighbors)
4
FACE CENTERED CUBIC STRUCTURE (FCC)
• Close packed directions are face diagonals.
--Note: All atoms are identical; the face-centered atoms are shaded
differently only for ease of viewing.
• Coordination # = 12
6
BODY CENTERED CUBIC STRUCTURE (BCC)
• Close packed directions are cube diagonals.
--Note: All atoms are identical; the center atom is shaded
differently only for ease of viewing.
• Coordination # = 8
8
HEXAGONAL CLOSE-PACKED
STRUCTURE (HCP)
• ABAB... Stacking Sequence
• 3D Projection
• 2D Projection
A sites
B sites
A sites
Adapted from Fig. 3.3,
Callister 6e.
• Coordination # = 12
• APF = 0.74
10
CERAMIC BONDING
• Bonding:
--Mostly ionic, some covalent.
--% ionic character increases with difference in
electronegativity.
• Large vs small ionic bond character:
Adapted from Fig. 2.7, Callister 6e. (Fig. 2.7 is adapted from Linus Pauling, The Nature of the
Chemical Bond, 3rd edition, Copyright 1939 and 1940, 3rd edition. Copyright 1960 by
Cornell University.
14
IONIC BONDING & STRUCTURE
• Charge Neutrality:
--Net charge in the
structure should
be zero.
--General form:
• Stable structures:
--maximize the # of nearest oppositely charged neighbors.
15
COORDINATION # AND IONIC
RADII
• Coordination # increases with
Issue: How many anions can you
arrange around a cation?
16
AmXp STRUCTURES
r cation 0.100

 0.8
• Consider CaF2 :
r anion 0.133
• Based on this ratio, coord # = 8 and structure = CsCl.
• Result: CsCl structure w/only half the cation sites
occupied.
• Only half the cation sites
are occupied since
#Ca2+ ions = 1/2 # F- ions.
18
STRUCTURE OF COMPOUNDS: NaCl
• Compounds: Often have similar close-packed structures.
• Structure of NaCl
• Close-packed directions
--along cube edges.
21
Diamond, BeO and GaAs are examples of FCC structures with two atoms per
lattice point