biomaterials

1. MSE-536
MSE 536: Introduction to Advanced
Biomaterials
Fall, 2010
Dr. R. D. Conner

2. 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.

3. MSE-536
1. Marrow stem cells could heal broken bones,
Betterhumans
2. Newly grown kidneys can sustain life in rats,
Bio.com
3. Doctors grow new jaw in man's back, CNN
4. FDA approves implanted lens for nearsightedness
, CNN
5. Stent recall may raise quality expectations,
Medical Device Link
Examples of Biomaterials in the News

4. MSE-536
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.

5. MSE-536
•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
A brief history of biomaterials

6. MSE-536
Biomaterials for Tissue
Replacements
• Bioresorbable
vascular graft
• Biodegradable nerve
guidance channel
• Skin Grafts
• Bone Replacements

7. A few examples…
composite foam seeded
with bone marrrow
stromal cells
Contact Lens
Bileaflet heart valve
prosthesis

8. Image of vascular grafts constructed of
expanded poly-tetrafluoroethylene (Teflon)
Image of blood clots on a bileaflet heart
valve
Problems with heart valves:
•Mechanical failure
•Blood clotting
•Tissue overgrowth

9. 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.

10. Schematic of a heart-
lung machine setup.
Potential Problems:
•High resistance in filter leads to high blood
pressure
•Low oxygenation efficiency
•Anticoagulants necessary to prevent clotting

11. MSE-536
• 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
Advanced and Future Biomaterials

12. MSE-536
Evolution of Biomaterials
Structural
Functional Tissue
Engineering Constructs
Soft Tissue
Replacements

13. Biological Responses to
Biomaterials
• Biocompatibility:
Incompatibility leads to: inflammation
redness
swelling
warmth
pain
Other reactions include: immune system
activation
blood clotting
infection
tumor formation
implant calcification
Protein
and
cellular
response
determine
success of
an implant

14. 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

15. Biomaterials is a $9 Billion
business in the U.S.
•Over 100,000 Heart
Valves
•300,000 Vascular grafts
•500,000 Artificial Joints

16. MSE-536
Metals
Semiconductor
Materials
Ceramics
Polymers
Synthetic
BIOMATERIAL
S
Orthopedic
screws/fixation
Dental
Implants
Dental Implants
Heart
valves
Bone
replacements
Biosensors
Implantable
Microelectrode
Skin/cartilage
Drug Delivery
Devices
Ocular
implants

17. Common Applications for Materials
Polymers
Metals
Ceramics

18. MSE-536
• Polymers fall into three categories:
– Elastomers (e.g. rubber bands)
– Composites
– Hydrogels (absorb/retain H2O)
Polymers
• 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

19. 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)

20. MSE-536
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

21. MSE-536
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

22. MSE-536
Biomaterial Processing
Techniques developed to change surface
chemistry while leaving bulk material
unchanged; e.g.:
•ceramic coatings on hips,
•coating a catheter with antibiotics

23. MSE-536
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

24. 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

25. 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 = hν

26. The distribution of the
hydrogen electron as
depicted by both the (a)
Bohr and (b) the wave-
mechanical models.
However, in the wave-
mechanical 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.

27. 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).

28. Order of filling
electron orbitals

29. The Periodic Table of
Elements

30. Atomic bonding
Tm = depth of well
E = d2
U/dr2
α is proportional to the
asymmetry in the
potential well
Ft = Fa + Fr
U = ∫Ft dr

31. • Bond length, r
• Bond energy, Eo
F
F
r
• Melting Temperature, Tm
Eo=
“bond energy”
Energy (r)
ro
r
unstretched length
r
larger Tm
smaller Tm
Energy (r)
ro
Tm is larger if Eo is larger.
PROPERTIES FROM BONDING: TM

32. • Elastic modulus, E
• E ~ curvature at ro
cross
sectional
area Ao
∆L
length, Lo
F
undeformed
deformed
∆LF
Ao
= E
Lo
Elastic modulus
E is larger if Eo is larger.
PROPERTIES FROM BONDING: E
• E ~ curvature at ro
r
larger Elastic Modulus
smaller Elastic Modulus
Energy
ro
unstretched length

33. • Coefficient of thermal expansion, α
• α ~ symmetry at ro
α is larger if Eo is smaller.
∆L
length, Lo
unheated, T1
heated, T2
= α (T2-T1)
∆L
Lo
coeff. thermal expansion
r
smaller α
larger α
Energy
ro
PROPERTIES FROM BONDING: α

34. Na (metal)
unstable
Cl (nonmetal)
unstable
electron
+ -
Coulombic
Attraction
Na (cation)
stable
Cl (anion)
stable
• Occurs between + and - ions.
• Requires electron transfer.
• Large difference in electronegativity required.
• Example: NaCl
IONIC BONDING

35. • Predominant bonding in Ceramics
Give up electrons Acquire electrons
He
-
Ne
-
Ar
-
Kr
-
Xe
-
Rn
-
F
4.0
Cl
3.0
Br
2.8
I
2.5
At
2.2
Li
1.0
Na
0.9
K
0.8
Rb
0.8
Cs
0.7
Fr
0.7
H
2.1
Be
1.5
Mg
1.2
Ca
1.0
Sr
1.0
Ba
0.9
Ra
0.9
Ti
1.5
Cr
1.6
Fe
1.8
Ni
1.8
Zn
1.8
As
2.0
CsCl
MgO
CaF2
NaCl
O
3.5
EXAMPLES: IONIC BONDING

36. • Requires shared electrons
• Example: CH4
C: has 4 valence e,
needs 4 more
H: has 1 valence e,
needs 1 more
Electronegativities
are comparable.
COVALENT BONDING
shared electrons
from carbon atom
shared electrons
from hydrogen
atoms
H
H
H
H
C
CH4

37. • Molecules with nonmetals
• Molecules with metals and nonmetals
• Elemental solids (RHS of Periodic Table)
• Compound solids (about column IVA)
He
-
Ne
-
Ar
-
Kr
-
Xe
-
Rn
-
F
4.0
Cl
3.0
Br
2.8
I
2.5
At
2.2
Li
1.0
Na
0.9
K
0.8
Rb
0.8
Cs
0.7
Fr
0.7
H
2.1
Be
1.5
Mg
1.2
Ca
1.0
Sr
1.0
Ba
0.9
Ra
0.9
Ti
1.5
Cr
1.6
Fe
1.8
Ni
1.8
Zn
1.8
As
2.0
SiC
C(diamond)
H2O
C
2.5
H2
Cl2
F2
Si
1.8
Ga
1.6
GaAs
Ge
1.8
O
2.0
columnIVA
Sn
1.8
Pb
1.8
EXAMPLES: COVALENT BONDING

38. 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.

39. There are two types of bonds: σ and π. σ
bonds occur along the participating orbitals
axis; π occur at right angles to the
participating orbitals

40. Bonds can also be “bonding” or “antibonding”
When forming molecular orbitals.
antibonding molecular orbitals have higher
Energy than bonding orbitals

41. (a) σ molecular orbitals. σ bonding
and antibonding molecular orbitals
describe the electron density in the
line between two nuclei. (b-c) π
molecular orbitals. π 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.

42. (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.

43. • Arises from a sea of donated valence electrons
(1, 2, or 3 from each atom).
• Primary bond for metals and their alloys
+ + +
+ + +
+ + +
METALLIC BONDING
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.

44. Arises from interaction between dipoles
• Permanent dipoles-molecule induced
• Fluctuating dipoles
+ - secondary
bonding
+ -
H Cl H Cl
secondary
bonding
secondary bonding
HH HH
H2 H2
secondary
bonding
ex: liquid H2asymmetric electron
clouds
+ - + -secondary
bonding
-general case:
-ex: liquid HCl
-ex: polymer
SECONDARY BONDING

45. Ceramics
(Ionic & covalent bonding):
Metals
(Metallic bonding):
Polymers
(Covalent & Secondary):
secondary bonding
Large bond energy
large Tm
large E
small α
Variable bond energy
moderate Tm
moderate E
moderate α
Directional Properties
Secondary bonding dominates
small T
small E
large α
SUMMARY: PRIMARY BONDS

46. 3
• 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...
METALLIC CRYSTALS

47. 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

48. 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.

49. Three simple lattices that describe metals are Face Centered Cubic (FCC)
Body Centered Cubic (BCC) and Hexagonal Close Packed (HCP)

50. 4
• Rare due to poor packing (only Po has this structure)
• Close-packed directions are cube edges.
• Coordination # = 6
(# nearest neighbors)
SIMPLE CUBIC STRUCTURE (SC)

51. 6
• Coordination # = 12
• Close packed directions are face diagonals.
--Note: All atoms are identical; the face-centered atoms are shaded
differently only for ease of viewing.
FACE CENTERED CUBIC STRUCTURE (FCC)

52. • Coordination # = 8
8
• Close packed directions are cube diagonals.
--Note: All atoms are identical; the center atom is shaded
differently only for ease of viewing.
BODY CENTERED CUBIC STRUCTURE (BCC)

53. 10
• Coordination # = 12
• ABAB... Stacking Sequence
• APF = 0.74
• 3D Projection • 2D Projection
A sites
B sites
A sites Bottom layer
Middle layer
Top layer
Adapted from Fig. 3.3,
Callister 6e.
HEXAGONAL CLOSE-PACKED
STRUCTURE (HCP)

54. 14
• Bonding:
--Mostly ionic, some covalent.
--% ionic character increases with difference in
electronegativity.
He
-
Ne
-
Ar
-
Kr
-
Xe
-
Rn
-
Cl
3.0
Br
2.8
I
2.5
At
2.2
Li
1.0
Na
0.9
K
0.8
Rb
0.8
Cs
0.7
Fr
0.7
H
2.1
Be
1.5
Mg
1.2
Sr
1.0
Ba
0.9
Ra
0.9
Ti
1.5
Cr
1.6
Fe
1.8
Ni
1.8
Zn
1.8
As
2.0
C
2.5
Si
1.8
F
4.0
Ca
1.0
Table of Electronegativities
CaF2: large
SiC: small
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.
• Large vs small ionic bond character:
CERAMIC BONDING

55. 15
• Charge Neutrality:
--Net charge in the
structure should
be zero.
--General form: AmXp
m, p determined by charge neutrality
• Stable structures:
--maximize the # of nearest oppositely charged neighbors.
- -
- -
+
unstable
- -
- -
+
stable
- -
- -
+
stable
CaF2: Ca2+
cation
F-
F-
anions+
IONIC BONDING & STRUCTURE

56. 16
• Coordination # increases with
Issue: How many anions can you
arrange around a cation?
rcation
ranion
rcation
ranion
Coord #
< .155
.155-.225
.225-.414
.414-.732
.732-1.0
ZnS
(zincblende)
NaCl
(sodium
chloride)
CsCl
(cesium
chloride)
2
3
4
6
8
COORDINATION # AND IONIC
RADII

57. 18
• Consider CaF2 :
rcation
ranion
=
0.100
0.133
≈ 0.8
• 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.
AmXp STRUCTURES

58. 21
• Compounds: Often have similar close-packed structures.
• Close-packed directions
--along cube edges.
• Structure of NaCl
STRUCTURE OF COMPOUNDS: NaCl

59. Diamond, BeO and GaAs are examples of FCC structures with two atoms per
lattice point