BN3301 Introduction to Biomaterials Li Jun, NUS

BN3301 INTRODUCTION TO BIOMATERIALS

Part II - Polymeric Biomaterials
1. Introduction to Polymers and Polymeric
Biomaterials

Prof. Li Jun
Department of Biomedical Engineering
(Email: jun-li@nus.edu.sg; Tel: 6516-7273; Office Location: EA-02-06)

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BN3301 Introduction to Biomaterials Li Jun, NUS

Biomaterials
Classification
Materials that are intended
to interface with Biomaterials

biological systems Metals

to evaluate, treat,
Ceramics
augment, restore, or
replace any tissue, Polymers
organ, or function of Biological Polymers

the body.
Synthetic Polymers

Composites

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Biomaterials

? Contact lens
Spectacles
Vascular graft
Crutches

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Polymers: High Molecular Weight Materials

Long chain high molecular weight materials formed from many small molecules called monomers

Polymers around us

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Naturally Occurring Polymers

Woods, rubber, cotton, wool, leather, and silk
Important materials used for many centuries
Proteins, enzymes, DNA/RNA, starches, and cellulose
Important in biological systems and physiological processes

DNA and RNA are

polyesters of H3PO4
Proteins are polyamides
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Synthetic Polymers: Early Industrial

Development
Natural rubber: 1839
Derivatives of cellulose: 1870
Synthetic polymers
1930 Styrene-butadiene rubber
1936 Poly(vinyl chloride), Poly(methyl methacrylate)
1937 Polystyrene
1939 Nylon-66 Nitrocellulose

1943 Polyethylene (branched), Nylon-6

1944 PET Implanting poly(methyl
1955 Polyethylene (linear) methacrylate) in body (1947)
1957 Polypropylene, Polycarbonate
1965 Polyimides
1974 Aromatic polyamides

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Synthetic Polymers as Biomaterials

First attempt to implant synthetic polymer in human body
Implanting a poly(methyl methacrylate) hip prosthesis (1947)
Biomedical implants
Orthopedic
Dental
Soft tissue
Cardiovascular, etc.
Prosthetic materials
Dressing materials
Extracorporeal devices
Encapsulants

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Polymers in Current Clinical Applications

Application Properties and design requirements Polymers used

Dental Stability and corrosion resistance, plasticity PMMA-based resins for

Strength and fatigue resistance, coating activity fillings/prosthesis
Good adhesion/integration with tissue polyamides
Low allergenicity poly(Zn acrylates)
Ophthalmic Gel or film forming ability, hydrophilicity Polyacrylamide gels
Oxygen permeability PHEMA and copolymers

Orthopedic Strength and resistance to mechanical PE, PMMA

restraints and fatigue PLA, PGA, PLGA
Good integration with bones and muscles
Cardiovascular Fatigue resistance, lubricity, sterilizability Silicones, Teflon
Lack of thrombus, emboli formation poly(urethanes), PEO
Lack of chronic inflammatory response
Drug delivery Appropriate drug release profile PLGA, EVA, silicones,
Compatibility with drug, biodegradability HEMA, PCPP-SA

Sutures Good tensile strength, strength retention Silk, catgut

Flexibility, knot retention, low tissue drag PLGA, PTMC-GA
PP, Nylon

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Potential Applications of Polymeric Biomaterials

Outside the traditional areas of plastic and reconstructive surgery, dentistry,

and bone or muscle repair, polymeric biomaterials are expected to play a
greater role in other areas:

Artificial organs and tissue engineering/regeneration

Drug carriers and controlled drug delivery
Polymeric gene delivery and gene therapy

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Synthetic Polymers as Biomaterials

Hydrophobic, non-water-absorbing materials

Silicone rubber (SR), polyethylene (PE), polypropylene (PP),
poly(ethylene terephthalate) (PET), polytetrafluoroethylene
(PTFE), and poly(methyl methacrylate) (PMMA) , etc.
More polar materials
Poly(vinyl chloride) (PVC), copoly(lactic-glycolic acid) (PLGA),
and nylons, etc.
Water-swelling materials
Poly(hydroxyethyl methacrylate) (PHEMA), etc.
Water-soluble materials
Poly(ethylene glycol) (PEG or PEO), etc.

Hydrolytically unstable and degrade in the body while

others may remain essentially unchanged for the lifetime Which is
of the patient. hydrophilic?
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Advantages of Polymers for Biomedical

Applications

Availability
- Huge number of polymers are available or potentially available
Ease of fabrication into many different forms
- Films, tubes, fibers, textiles, and solids, gels, solutions
Excellent flexibility for fabricating soft tissues
Very low or non-toxicity to human body
Light density
Low prices

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Disadvantages of Polymers for Biomedical

Applications

Low modulus of elasticity and viscoelastic characteristics make the

polymers difficult to use for large load-bearing applications.
The nature of polymerization makes them degradable in the body.
It is very hard to obtain pure medical grade polymers without additives
such as antioxident, antidiscoloring agents, and plasticizers because
most polymers are produced in large quantities for other purposes
except in very limited cases.

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Requirements for Selecting Polymers as Biomaterials

Properties Description

Biocompatibility Non-carcinogenesis, nontoxicity, and nonallergic response

Sterilizability Autoclave, dry heating, ethylenoxide gas, and radiation

Physical propert Strength, elasticity, and durability

Manufacturability Machining, molding, extruding, and fiber forming

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Polymer Molecules
Polymer molecules are very large: macromolecules
Long chain high molecular weight materials formed from many
- small molecules called monomers
- small repeat chemical units called mer (Polymer Many mers)
Monomer refers to a stable molecule or starting material from which a polymer is
formed or synthesized.
The repeat unit of the polymer is usually equivalent or nearly equivalent to the
monomer.

Mer (repeat unit)

Polyethylene
Right: a schematic representation of mer and chain structures.
Left: a perspective of the polymer molecule, indicating the zigzag backbone structure.
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Polymer Molecules
Most polymer consists of
long and flexible chains
with a string of C atoms as
a backbone.
Side-bonding of C atoms
are H atom or radicals.
Double bonds possible in
both chain and side bonds.

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Polymer Molecules Copolymer

When all the mers are the same, the

Random copolymer
molecule is called a homopolymer.
When there is more than one type of
mer present, the molecule is a
copolymer, which can differ in the Alternating copolymer
way the mers are arranged.
- Random copolymer: two different units
are randomly dispersed along the Block copolymer
chain.
- Alternating copolymer: Two mer units
alternate chain position.
- Block copolymer: Identical mers are Graft copolymer
clustered in block along the chain.
- Graft copolymer: Homopolymer side
branches are grafted to another
homopolymer main chain.

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Polymer Synthesis: Polymerization Processes

Three types of reactions:

1) Addition (chain-reaction) polymerization
Monomer containing a double bond polymerizes via addition
reaction.
2) Ring opening polymerization
Cyclic monomer opens to form a linear chain.
3) Condensation (step-reaction) polymerization
Polymers are formed via condensation reaction, a small
molecule (H2O, HCl, CO2, etc.) is eliminated in the reaction.

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Addition (chain-reaction) Polymerization

Synthesis of Addition Polymers
Double bond opens up, two electrons are used to form two new C-C
single bonds connecting monomers.

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Addition (chain-reaction) Polymerization

Synthesis of Addition Polymers
By modifying the monomer a variety of polymers can be made.

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Rubber A Naturally Occurring Addition Polymer

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Ring Opening Polymerization

A cyclic monomer opens to form a linear chain

Catalyst

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Condensation (or step reaction) Polymerization

Two molecules join to form a larger molecule by eliminating a small molecule

such as water

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Condensation (or step reaction) Polymerization

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Addition polymers?
Condensation polymers?

Mer Structure for Some Common Polymeric Materials

Polymer Repeating (Mer) Polymer Repeating (Mer)
Structure Structure

Polyethylene (PE) Polymethyl methacrylate (PMMA)

Polyvinyl chloride (PVC) Phenol-formaldehyde (Bakelite)

Polytetrafluoroethylene (PTFE) Polyhexamethylene

adipamide (Nylon 66)

Polypropylene (PP) Polyethylene terephthalate

(PET, a polyester)

Polystyrene (PS) Polycarbonate

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Classifications or Types of Polymers

Plastic: materials that can be formed into shapes
Thermoplastic: materials that can soften on heating, and can be shaped
more than once, such as poly(ethylene terephthalate) (PET) used as
replacements for blood vessels.
Thermosetting plastic (thermoset or resin): materials that harden when
two components are mixed together (often with heating or UV-irradiation),
and can only be shaped once, such as cements used in dental devices and
orthopedics such as hip replacements.

Elastomer or rubber: materials that are elastic in some way

If a moderate amount of deforming force is added, the elastomer will deform,
which can return to its original shape when the force is released.
(Used as catheters, and for covering leads on implanted electronics, like
pacemaker.)

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Polymer Molecular Characteristics

- Polymer Properties are dependent on polymer molecular characteristics

Chemistry (mer composition, identity of side groups)

Chain length (molecular weight or size)
Molecular shape (chain twisting, entanglement, etc.)
Structure, orientation of chains (linear, branched, crosslinked, network,
etc.)

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Chain Length
Polymers - long chain molecules of high molecular weight
n State Use
H -(CH2)n- H

1-4 gas burned for energy

5-11 liquid gasoline

9-16 med. visc. kerosene
liquid
16-25 hi visc. liq. oil, grease
25-50 solid paraffin wax
1000- tough plastic PE bottles, containers
3000

Two main ways of defining average molecular weight

Number average molecular weight
Weight average molecular weight
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Chain Length
(a) Number average molecular weight (Mn)
Obtained by dividing the chains into a series of size range and then determining
the number fraction of chains within each size range.
Mn = xiMi
Where Mi represents the mean (middle) molecular weight of size range i, and xi is fraction
of chains of the total number of chains within the corresponding size range.

(a) (b)

Hypothetical polymer
molecular size
distributions on the
basis of (a) number
and (b) weight
fraction of molecules.

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Chain Length
(b) Weight average molecular weight (Mw)

Based on the weight fraction of molecules within the various size ranges.
Mw = wiMi
Where Mi represents the mean (middle) molecular weight of size range i, and wi is weight
fraction of molecules within the same size interval.

(a) (b)

Hypothetical polymer
molecular size
distributions on the
basis of (a) number
and (b) weight
fraction of molecules.

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Chain Length
A typical molecular weight distribution
along with the average molecular
weights (Mn and Mw)
Synthetic polymers possess different
molecular weight distributions

Ni

Mi weight
Molecular

polydispersity index = Mw/Mn

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Chain Length

Degree of Polymerization
Alternative way to express average polymer chain size is degree of
polymerization the average number of mer units in a chain.

Number-average nn = Mn / m

Weight-average nw = Mw / m

Where Mn and Mw are the number-average and weight-average molecular weights as

defined above, where m is the mer molecular weight. For a copolymer (having two
or more different mer units), m is determined from
m = fj mj
fj and mj are, respectively, the chain fraction and molecular weight of mer j.

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Molecular Shape of Polymer Chains

The angle between the singly bonded carbon atoms is ~109

carbon atoms form a zigzag pattern in a polymer molecule.

Moreover, while maintaining the 109 angle between bonds,

polymer chains can rotate around single C-C bonds (double
and triple bonds are very rigid).

Random kinks and coils lead to entanglement,

like in the spaghetti or noodle structure.

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Molecular Shape of Polymer Chains

Molecular chains may thus bend, coil, and kink.

Neighboring chains may intertwine and entangle.
Large elastic extensions of rubbers correspond to unraveling of these coiled
chains.
Mechanical / thermal characteristics depend on the ability of chain segments to
rotate.

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Molecular Structure of Polymer Chains

The physical characteristics of polymer material depend not only on molecular weight
and shapes, but also on molecular structures:

Linear polymers: Those in which the mer units are jointed together end to end in single
chains.
These long chains are flexible and may be thought of as a mass of spaghetti.
Van der Waals and hydrogen bonding between polymer chains.
Examples: polyethylene, polyvinyl chloride, polystyrene, nylon, etc.

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Molecular Structure of Polymer Chains

Branched polymers: Polymers in which side-branch chains are connected to the main ones.
The chain packing efficiency is reduced with the formation of side branches compared to
liner polymers lower polymer density.

Those polymers that form liner structures may also be branched.

Example: low density polyethylene (LDPE).
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Molecular Structure of Polymer Chains

Crosslinked polymers: Polymers in which adjacent liner chains are jointed one to another
at various position by covalent bonds.
Often achieved by adding atoms or molecules that form covalent links between chains.
Many rubbers have this structure.
cis-Polyisoprene, the
main constituent of
natural rubber

Rubber latex
from a
rubber tree

Two strains (blue

and green) of
natural rubber after
vulcanization with
elemental sulfur

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Molecular Structure of Polymer Chains

Network polymers: Trifunctional mer units, having three active covalent bonds, form 3D
network.
Actually, a polymer that is highly crosslinked may be classified as a network polymer.
Theses materials have distinctive mechanical and thermal properties.
Example: epoxy resin, phenol-formaldehyde resin.

Phenol-formaldehyde
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Molecular Configuration
Polymers having more than one side group of atoms bonded to the
main chain, the regularity and symmetry of the side groups
arrangement can significantly influence the properties.

There are two types of isomerism:

Stereoisomerism
Geometrical isomerism

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Molecular Configuration
Stereoisomerism: atoms are linked together in the same order, but can
have different spatial arrangement.
1) Isotactic configuration: all side
groups R are on the same side of
the chain.

2) Syndiotactic configuration: side

groups R alternate sides of the
chain.

3) Atactic configuration: random

orientations of group R along the
chain.
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Molecular Configuration
Geometrical isomerism
Consider two carbon atoms bonded by a double bond in a chain.
H atom or radical R bonded to theses two atoms can be on the same side
of the chain (cis structure) or on opposite sides of the chain (trans
structure)

cis-polyisoprene trans-polyisoprene

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Summary: Polymer Molecular Characteristics

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Solid State Properties

Polymers can be either amorphous or
semi-crystalline.
Amorphous glassy state
hard, brittle
no melting point

Semi-crystalline glassy state

hard, brittle
crystal formation when cooled
exhibit a melting point Crystallinity affects physical properties:
Crystalline polymers are stiffer, harder, more
dense
These properties make semi-crystalline polymers
(often referred to simply as crystalline polymers) Crystallinity affects optical properties:
desirable materials for biomedical applications. 1) Amorphous polymers are transparent
(glasslike)
(Examples: PE, PP, PTFE, and PET)
2) Partly crystalline and partly glassy
polymers are translucent

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Tg

Solid State Properties Tm

Thermal Properties
Noncrystalline polymer (amorphous)

In the liquid or melt state, a noncrystalline

polymer possesses enough thermal energy
for long segments of each polymer to move
randomly (Brownian motion).
Glass transition temperature (Tg) is the
temperature at which all long range
segmental motions cease (frozen).
Polymers have high Tg, such as PMMA, tend
to be hard and glassy (at room temperature);
Polymers have low Tg, such as silicone
rubber (SR), are rubbery (when crosslinked).

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Tg

Solid State Properties Tm

Thermal Properties
Crystalline polymer (semi-crystalline)

Polymers with any crystallinity will also

exhibit a melting temperature (Tm) owing
to melting of the crystalline phase.
These semi-crystalline polymers, such as
PET, PP, and nylon, are usually strong.
All polymers have a Tg, but only semi-
crystalline polymers exhibit a Tm.
The Tg is always below the Tm.

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Solid State Properties

Mechanical Properties
Tensile properties of polymers can be characterized by their deformation
behavior (stress-strain response).

Amorphous and rubbery polymers are soft and

reversibly extensible.
- The freedom of motion of the polymer chain is retained
at a local level, while a network structure (resulting
from chemical cross-links and chain entanglements)
prevents large-scale movement or flow.
- Thus, rubbery polymers tend to exhibit a lower modulus
or stiffness, and extensibilities of several hundred
percent.

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Solid State Properties

Mechanical Properties
Glassy and semi-crystalline polymers have higher
moduli and lower extensibilities.
The ultimate strength of polymers is the stress at or
near failure.
For most materials, failure is catastrophic (complete
breakage).
- However, for some semi-crystalline materials, the
failure point may be defined by the stress point where
large inelastic deformation starts (yield point).
The toughness of a polymer is related to the energy
absorbed at failure and is proportional to the area
under the stress-strain curve.

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Mechanical Properties of Polymers

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Summary
Synthetic polymers are a class of important and unique biomaterials,
having many advantages over other types of biomaterials.
Polymers are formed by small repeat units (mers), and synthesized by
a few different types of polymerization processes.
Polymers can be plastics and elastomers.
Polymer properties are determined by chemical composition, chain
length, molecular shape, and other structural factors.
The solid properties of polymers (including thermal and mechanical
properties) are further affected by crystallinity and crosslinking.

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