Biomaterials, Artificial Organs and

Tissue Engineering

Chapter 10

Biomedical Polymers

Dr Robert Hill
Imperial College London
 Biomedical Polymers

• Generally high molecular weight polymers that do not degrade

in the body can be classified as bioinert.
• Most problems that occur are due to leaching of plasticisers and
additives.
• It is important to characterise the grade in use. What is sold as
polymer X by one manufacturer may be very different from
polymer X sold by another due to purity and additives present.
• Surface reactions and absorption of proteins can cause
problems.
• Surface texture and form of the implant are important.
 Common non-degradable (bio-inert)
medical polymers
• Polyethylene terephthalate (PET), Dacron.
• Nylon 6,6.
• Polyurethanes.
• Polytetrafluoroethylene (PTFE).
• Polyethylene (low density and high density) plus UHMW.
• Polysiloxanes (silicones).
• Poly(methylmethacrylate).

Note there is some evidence of enzymatic degradation of the

first four types but the amount of degradation in most cases
is very small, the exception being some types of
polyurethane.
 Poly(methylmethacrylate) PMMA

• Hard rigid glassy but brittle polymer.

• Classified as bioinert. CH3
• In set form used as intraocular lenses |
and hard contact lenses. [ - CH2-C- ]n
• In situ setting forms (cold curing) are |
used as bone cements. C=O
|
• Shrinkage occurs on polymerisation.
O
• Shrinkage largely offset by water |
absorption. CH3
• Exothermic polymerisation which can
lead to thermal bone necrosis.
Figure 10.1
 Total Hip Replacement

Pelvis

Acetabular Cup

Femoral
Head

Femur
Bone Cement

Femoral Stem
Figure 10.2
 Polytetrafluoroethylene (PTFE)

• It has the chemical structure [-CF2-CF2]n.

• PTFE is chemical extremely stable and is a classic example of a bioinert
polymer.
• Commercial polymers approximate to PTFE.
• It is highly crystalline and the crystallites have high melting point
(330oC). This makes PTFE difficult to process.
• It cannot be moulded to shape. Particles are sintered then machined to
the required form.
• Gortex is a fibrous sheet form of PTFE that has numerous uses as a
membrane material.
• PTFE has relatively poor mechanical properties with a low yield
strength, which limits its use to non structural applications.
• It is used as part of vascular prostheses in the form of coatings on
Dacron.
 Polyethylene (PE)
• Polyethylene has the chemical structure [-CH2-CH2]n.
• Three types find use:
– Low density polyethylene LDPE( lower degree of crystallinity).
– High density polyethylene HDPE (higher degree of crystallinity).
– Ultra high molecular weight polyethylene UHMWPE (molar mass >10 6).
• PE has too low a yield strength for most structural applications. The yield
strength increases with molecular weight and degree of crystallinity.
• PE like PTFE is a bioinert polymer.
• PE is a hydrophobic polymer.
• LDPE and HDPE are readily mouldable. UHMPE is not and like PTFE is
sintered and machined to shape.
• UHMWPE is used as the bearing surface, the acetabular component of
hip joints and is only used in orthopaedics.
• However UHMWPE particles are very toxic and cause bone necrosis and
osteolyic lesions, which are a major contributing factor to the failure of
hip joints.
 Polysiloxanes (Silicones)

• Widely used.
• Long track record of use.
• Material types include elastomers, gels, lubricants, foams
and adhesives.
• Very chemically stable and unreactive.
• Very hydrophobic.
• Low moisture uptake.
• Polymer of choice for long term use in the body where an
elastomer is required and there is a demand for
biodurability and biocompatibility.
• Good electrical insulation characteristics.
 Polysiloxanes (Silicones)

Nearly all are based on polymethylsiloxane.

CH3
|
[-O-Si-]n
|
CH3
Note the lack of any polar groups. This leads to a very
hydrophobic polymer with poor wetting characteristics.
Polymethylsiloxane is rarely used without modification.
 Polysiloxane Elastomers

• These consist of a cross-linkable modified polysiloxane of

high molar mass (>3.5 x105) a reinforcing filler and a catalyst
system to initiate cross-linking.
• These materials only flow easily under pressure and are
fabricated by techniques such as compression moulding
transfer moulding calendering and extrusion.
• Low molecular weight grades (<105) can be fabricated by
solvent casting and reactive injection moulding.
• Vulcanization/cross-linking systems may involve benzoyl
peroxide, platinum catalysts and room temperature moisture
curing (RTVs).
 Polysiloxane Gels

• These are similar to the elastomers but contain no filler

and are generally based on a low molar mass
polymethylsiloxane that is very lightly cross-linked.
• Used in breast implants some problems with uncross-
linked low molar mass chains and impurites “bleeding”
permeating the envelope by osmotic driven diffusion.
• They are not recommended for use except when contained
by an impervious envelope.
 Polysiloxane Adhesives

Two basic types:

1. Those that cure and cross-link on contact with water.
e.g Silastic Medical Adhesive type A.
This type contains acetoxy ligands that react with water to form
silicon-oxygen-silicon cross-links and acetic acid. There is some
evidence of a slight reaction to the acid produced when leached.
2. Those that rely on their”stickiness” only for adhesion e.g.
Dow Corning 355.
This type is contained within a fluorocarbon solvent. It can be used to
affix materials to the skin, metals paper, glass, fabric, polysiloxane
and elastomers. Its adhesive properties to polysiloxanes are not good
over long time periods because the solvent diffuses into the
polysiloxane.
 Polyamides (Nylon)

• Based on –CONH– linkages.

• Major types based on Nylon 6 and Nylon 6,6.
• Fibres and mouldings partially crystalline – crystallinity
influences properties.
• Fairly hydrophilic.
• Takes up water and properties change.
• Kevlar is a polyaromatic nylon giving rise to high strength
fibres – controversy over biocompatibility.
 Poly(ethyleneterephthalate) (PET)

• Relatively hydrophilic protein absorption and

thrombogenicity increases with hydrophobic character.
• PET is better for blood contacting devices than polyamides
since amides have a tendency to degrade.
• Dacron is based on amorphous PET fibres.
• The tightly knit forms support maximal cell coverage
whereas loose knits do not support tissue ingrowth.
 Poly(ethylene terephthalate) (PET)

Figure 10.3. Structure of PET. Note the ester grouping. This is

an example of an aromatic ester. Aromatic esters are generally
not degradable in the body.
 Polyurethanes

Polyurethanes are polymers that contain the urethane group.

H
|
-N - C - O –
||
O
A large number of urethane polymers with widely different
physical and biological properties exist.
 Polyurethanes synthesis

The urethane grouping can be considered as resulting

from the reaction of an isocyanate and an alcohol:

R’-N=C=O + R - OH R’-N-C-O-R
| ||
HO

The polyurethane is then represented by:

[-R-O-C -NH -R-HN-C-O-]n

|| ||
O O
• The wide variety of polyurethanes lies with the numerous
possibilities for R and R.
• R is typically an oligomeric(molar mass 200–500) hydroxyl
terminated polyether or polyester.
• Generally a two stage synthesis involving the preparation of a
low molar mass prepolymer followed by chain extension and
or cross-linking.
• Common prepolymers are based on 2,4-toluene diisocyanate
(TDI) or 4,4-diphenylmethane diisocyanate (MDI).
• Polyether urethanes are usually based on polytetramethylene
oxide (PTMO) polypropylene oxide (PPO) and polyethylene
oxide (PEO).
• Polyester urethanes are typically based on polycaprolactones.
 Chain extension in polyurethanes

• Chain extension may be performed by glycols or

diamines.
• The nature of the chain extender is very important in that
it determines chain flexibility and modulus.
• It is also possible to have urea groups -NH-CO-NH- as
well as the urethane group -NH-CO-O-.
• Most polyurethanes for medical use are two phase block
copolymers (also termed segmented polyurethanes). The
polyester or polyether glycol forms the soft segment and
matrix phase.
 Polyurethanes in the body
• In the early use of polyurethanes acute reactions were
observed on implantation. Most of the studies were done on
commercial products rather than well characterised materials.
The reactions observed are now believed to be due to in vivo
ester hydrolysis of polyester urethanes.
• Problems have also occurred with rejection of breast implants
coated with polyester urethanes due to degradation of the
urethane.
• Segmented polyether urethanes are preferred because of their
greater stability and lack of susceptibility to hydrolysis.
Commercial examples include Biomer, Pellethane and
Tecoflex.
• Segmented polyether urethanes have good
haemocompatibility and are one of the preferred polymer
types for blood contacting devices.
Biodegradable Polymers
or
Hydrolysable Polymers
 Bioresorbable

• A bioresorbable material is designed to degrade within the

body after performing its function.
• Useful materials often degrade to give normal metabolites
of the body. Examples include:
– Polylactide.
– Polyglycolide.
– Poly(-3-hydroxybutyrate).
– Polyhyaluronic acid Esters.
• Biodegradable/hydrolysable polymers are the basis of many
scaffolds for tissue engineering.
 Biodegradable Polymers
(Not Really Biodegradable!)

• Polyglycolic acid (polyglycolide).

• Polylactic acid (polylactide).
• Poly-3-hydroxybutyrate.
• Polydioxanone.
• Linear polyaliphatic esters.
• Copolymers of the above plus additional species e.g.
poly(glycolic acid/lactic acid) and poly(glycolide-
trimethylene carbonate).
 Degradation by Hydrolysis

• Polymers produced by a condensation route are prone to

hydrolysis. In addition polymers may contain side groups
that are capable of being hydrolysed.
• The rate of hydrolysis is dependent on the water
absorption of the polymer and is often limited by the
diffusion of water through the polymer.
• Diffusion of water in polymers is often related to their
solubility parameter, Tg and degree of crystallinity.
• Polyesters based on [-R-COO-]n are often susceptible to
hydrolysis.
• Degradation is pH dependent. Esters are hydrolysed at a
faster rate under acid and alkaline conditions. Acid is
produced on hydrolysis of an ester, so pH falls during
hydrolysis, accelerating the degradation process.
 Swelling and Dissolution

• Polymers when exposed to liquids may swell or dissolve.

• The small molecules of the liquid may diffuse into the
polymer pushing the chains apart and increasing the
volume. This may occur preferentially at scratches on the
surface leading to a local tensile stress and crazing or
environmental stress cracking. Dissolution may be viewed
as an extreme case of the above.
• Degradation by this route is reduced by:
– Cross-linking.
– Increasing molar mass.
– Increasing the degree of crystallinity.
– Reducing the temperature.
 Polyglycolide and Polylactide

• Poly(-hydroxy acid)s are a group of polymers whose

repeating unit is based on -(O-CO-CHR)-n and are derived
from -hydroxy acids HO-CHR-COOH. They have been
under development for osteosynthesis devices since the
1960s.
• Polyglycolide is widely used for degradable sutures.
Implants have been fabricated from both polyglycolides
and polylactides. Both polymers are polyesters and possess
an ester group in the polymer backbone that can be
hydrolysed. The degradation products of these two
polymers are glycolic acid and lactic acid respectively, both
occur naturally in the body.
 Polyglycolide
• Based on (O-CO-CHR)-n where R=H
• High MW PGA is a hard tough crystalline Tm ~ 228oC, Tg ~
37oC. The polymer can be spun to produce fibres when the
molar mass is between 2 × 104 and 1.45 × 105. The strength of
PGA in the fibre direction is increased when spun into fibres,
because of the preferred molecular orientation of the polymer
chains  sutures.
• High MW PGA is made by dehydrating hydroxyacetic acid
glycolic acid to form glycolide the cyclic dimer condensation
product. PGA can be synthesised from glycolide under the
influence of metal salt catalysts at low concentration by a ring
opening polymerisation. The molar mass of the polymer is
determined by temperature, time, concentration of catalyst and
concentration of any chain transfer agents.
 Degradation of Poly(glycolic acid)

• Poly(glycolic acid) (PG) has a lower Tg than PHB or PET

and a higher water absorption.
• PG degrades by hydrolysis
• Sutures (stitches) made from spun PG fibres degrade in
about 20 days in the body
 Polylactides
• -(O-CO-CHR)-n where R=CH3.
• Replacing H by CH3 leads to a more hydrophobic polyester
and results in lower water uptake and lower hydrolysis rates.
• R=CH3 results in a chiral centre and leads to D and L forms
as well as DL racemic forms where there is a random
arrangement of chiral centres.
• D and L forms can crystallise but the racemic form cannot.
• The degree of crystallinity influences strength, fracture
toughness and degradation behaviour. The crystalline
regions do not take up much water and are much more
resistant to degradation. This can result in crystallites giving
rise to particulate debris following degradation.
 Degradation of polylactides

• Degradation is often autocatalytic.

• Degradation of thick sections can occur faster than thin
sections due to the build up of a localised low pH
accompanying degradation within the section.
• This can result in the rapid release of lactic acid and
polylactide oligomers resulting in a toxic response.
• This is overcome by using basic fillers which neutralise
the acidic carboxyl groups produced on hydrolysis.
• Applications for polylactides include bone plugs, screws
and fracture fixation plates.
• Applications are limited as a result of rapid reduction in
strength in vivo.
 Poly-3-hydroxybutyrate (PHB)

• Poly(3-hydroxybutyrate) will be considered as an

example of the potential of biotechnology for producing
new materials and of the advantages of biological
synthesis.
• It has many properties that are attractive for biomedical
applications. In particular it is a polyester like
polyglycolide, the material used for sutures and is also
biodegradable within the body.
 Degradation of PHB

• Poly(3-hydroxbutyrate) PHB is a polymer produced by

a bacterium.
• PHB is similar to PET in terms of good mechanical
properties.
• PHB has a Tg of about 10oC.
• PHB is less hydrophobic than PET and its water
absorption is higher.
• PHB degrades by hydrolysis
• PHB can undergo degradation in soil making it
attractive as a degradable packaging material. The
degradation is facilitated by soil bacteria.
 Structure of Poly-3-hydroxybutyrate
• PHB is an ester.
• Similar structure to PET.
• Note the chiral centre.
CH3 O • Biosynthesis gives ideal
| || stereochemistry leading to high
[
-C*-CH2-C-O- ]n degree of crystallinity >95%
• Copolymers with hydroxyvalerate
| can be produced.
H • Degradation product is
Figure 10.4
hydroxybutyric acid – a normal
metabolite.
• It may degrades too slowly for
biomedical applications
Properties of Degradable Polyesters
(compared to PET)

Table 10.1
Property PHB PEA PET
Glass Transition 15 -48 98
Temperature ( C )
Crystalline Melting 175 50 234
Temperature ( C )
Maximum % 95 40 55
Crystallinity
Optically Active / x x
Biodegradable / x x
 Hyaluronic Acid

• Hyaluronic acid is an important biopolymer and bridges

the gap between synthetic and naturally occurring
polymers well as the gap between biochemistry and
synthetic polymer chemistry.
• Hyaluronic acid is also an example of a commercially
useful biopolymer with many existing and potential uses as
a biomedical material.
• It is also a very important extracellular biological
polysaccharide and plays a major role in regulating the
environment in which many cells exist.
 Hyaluronic Acid

• Being a polysaccharide it does not have a monodisperse

molecular weight distribution and its structure is not
determined by the genetic code.
• Furthermore, because it is a polysaccharide, it does not
elicit an immune response. Its molar mass and molar mass
distribution determine its mechanical properties.
• Being a naturally occurring polysaccharide, Hyaluronic acid
is completely biodegradable in vivo, which makes it suitable
as a matrix for controlled drug delivery and as a matrix for
hybrid implants consisting of living cells in a hydrogel
matrix.
 Hyaluronic Acid

• It is also a very suitable material for non-adhesive wound

dressings.
• Hyaluronic acid is a very important connective tissue
biopolymer.
• It is important to note that most cells do not exist in
crystalline matrices or free solution, but in hydrogels and
that the commonest naturally occurring hydrogel is based on
hyaluronic acid.
 Hyaluronic acid in the body
Hyaluronic acid is found naturally as
• the largest part of the extracellular matrix
• an integral part of the aqueous humor of the eye,
• an integral part of synovial fluid of the joints where it exerts rheological
control and serves as a viscoelastic damping medium.
Hyaluronic acid
• controls the water content of the extracellular fluid,
• serves to resist bacterial penetration, whilst allowing molecules to gain
access to the cell and exit from the cell.
• binds cations and strongly influences cell mobility and tissue regrowth.
The properties of hyaluronic acid gels are determined by their
molar mass, molar mass distribution and concentration,
which largely determines the mesh density and permeability.
 Structure of Hyaluronic Acid

D Glucoronic Acid N-Acetyl-D-Glucosamine

Figure 10.5
 Properties of Hyaluronic Acid
• The properties of hyaluronic acid can be modified.
• Commercial hyaluronic acids are extracted from rooster
combs, but hyaluronic acids are now produced using
biochemical engineering from genetically engineered
bacteria. The molar mass of the hyaluronic acid can be varied
to alter the viscosity and gel properties and the basic
hyaluronic structure can be modified by:
– esterification with hydrophobic groups
– crosslinking.
• Increasing the hydrophobicity and degree of cross-linking
reduces the water uptake reduces the expansion and reduces
the degradability. This enables the properties of commercial
hyaluronic acids to be tailored to given applications.