MSE-536

MSE 536: Introduction to Advanced Biomaterials

Fall, 2010

Dr. R. D. Conner

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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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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

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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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•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

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Biomaterials for Tissue Replacements

• Bioresorbable vascular graft

• Biodegradable nerve guidance channel

• Skin Grafts• Bone Replacements

A few examples…

composite foam seeded with bone marrrow

stromal cells

Contact Lens

Bileaflet heart valve prosthesis

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

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 heart-lung machine setup.

Potential Problems:•High resistance in filter leads to high blood pressure

•Low oxygenation efficiency

•Anticoagulants necessary to prevent clotting

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• 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

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Evolution of Biomaterials

Structural

Functional Tissue Engineering Constructs

Soft Tissue Replacements

Biological Responses to Biomaterials

• Biocompatibility: Incompatibility leads to: inflammation

rednessswellingwarmthpain

Other reactions include: immune system activation

blood clottinginfectiontumor formationimplant

calcification

Protein and cellular

response determine success of an implant

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

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Metals

Semiconductor Materials

Ceramics

Polymers

Synthetic BIOMATERIAL

S

Orthopedic screws/fixation

Dental Implants

Dental Implants

Heart valves

Bone replacements

BiosensorsImplantable Microelectrode

Skin/cartilageDrug Delivery Devices

Ocular implants

Common Applications for Materials

Polymers

Metals

Ceramics

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• 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

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)

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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

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 MaterialsThe 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 = h

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.

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

Tm = depth of well

E = d2U/dr2

is proportional to the asymmetry in the

potential well

Ft = Fa + Fr

U = ∫Ft dr

• 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

• Elastic modulus, E

• E ~ curvature at ro

cross sectional area Ao

L

length, Lo

F

undeformed

deformed

L F 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

• Coefficient of thermal expansion,

• ~ symmetry at ro

is larger if Eo is smaller.

L

length, Lo

unheated, T1

heated, T2

= (T2-T1) L Lo

coeff. thermal expansion

r

smaller

larger

Energy

ro

PROPERTIES FROM BONDING:

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

• 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

• 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

• 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

colu

mn IVA

Sn 1.8Pb 1.8

EXAMPLES: COVALENT BONDING

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: and . bonds occur along the participating orbitals axis;

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) molecular orbitals. bonding and antibonding molecular orbitals

describe the electron density in the line between two nuclei. (b-c)

molecular orbitals. 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.

• 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.

Arises from interaction between dipoles

• Permanent dipoles-molecule induced

• Fluctuating dipoles

+ - secondary bonding + -

H Cl H Clsecondary 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

Ceramics(Ionic & covalent bonding):

Metals(Metallic bonding):

Polymers(Covalent & Secondary):

secondary bonding

Large bond energylarge Tm

large Esmall

Variable bond energymoderate Tm

moderate Emoderate

Directional PropertiesSecondary bonding dominates

small Tsmall Elarge

SUMMARY: PRIMARY BONDS

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• 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

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)

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• Rare due to poor packing (only Po has this structure)• Close-packed directions are cube edges.

• Coordination # = 6 (# nearest neighbors)

SIMPLE CUBIC STRUCTURE (SC)

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)

• Coordination # = 8

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• 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)

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• 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)

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• 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 2.5Si 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 byCornell University.

• Large vs small ionic bond character:

CERAMIC BONDING

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• 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

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• Coordination # increases with Issue: How many anions can you arrange around a cation?

rcationranion

rcationranion

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

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• Consider CaF2 :

rcationranion

0.1000.133

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

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• Compounds: Often have similar close-packed structures.

• Close-packed directions --along cube edges.

• Structure of NaCl

STRUCTURE OF COMPOUNDS: NaCl

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