Transcript Polymers for Medical Applications

Polymers for Medical
Applications
1. Polymers for Artificial Joints
2. Bioabsorbable Polymers for
surgical applications
3. Adhesives for medical
applications
1. Polymers for Artificial Joints
Figure (a) Normal joint
Figure (b) replacement
of the joint is required
There are several regenerative treatments,
but joint replacement with an artificial joint is
the most common and effective treatment
Modern Total Arthoplasty
The artificial joint has a sliding interface using a combination of
a hard material against a soft material.
Hard material: Metallic femoral head
Soft material: Polytetrafluoroethylene (PTFE) shell
Cement material: cold-curing acrylic cement
(polymethylmethacrylate)- to fix the components and
to transfer the stress more uniformly
SOFT MATERIALS
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The soft material made of
polytetrafluoroethylene (PTFE), then it was
replaced by high density polyethylene
(HDPE) and later by ultra high molecular
weight polyethylene (UHMWPE).
UHMWPE was chosen because of its low
friction coefficient, high resistance to wear,
high impact resistance, high ductility and
stability in the body
Problems of Total Joint Replacement
What are the differences between
HDPE and UHMWPE???
The differences between HDPE and
UHMWPE
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Morphology – the chain length of the tie
molecules in UHMWPE is much higher than
that in HDPE
Molecular weight – UHMWPE shows
extremely high molecular weight (two to six
million), in contrast to 20,000 – 30,000 for
regular HDPE, LDPE & LLDPE.
Crystallinity & density of UHMWPE are lower
than that of HDPE, due to the high molecular
weight and chain structure
Chemical Structure
Properties of UHMWPE
Properties of UHMWPE
Processing of UHMWPE
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Fabrication methods for thermoplastics
cannot be applied for processing of
UHMWPE
When UHMWPE is melted (> crystalline
melting temp.), the resin becomes rubbery
but does not flow
Why the processing of UHMWPE is
complicated???
Processing of UHMWPE
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Require a combination of temperature, high
pressure and time.
Methods are ram extrusion, compression
molding and direct compression molding.
The objective of the methods is to apply
enough temperature and pressure to fully
sinter the UHMWPE particles
Processing of UHMWPE
Wear properties of UHMWPE
The abrasion resistance of UHMWPE is
The highest of the various materials
Relative weight loss vs.
type of polymers
Relationship between molecular weight
of polyethylene and abrasion weight loss
Abrasive wear resistance is increased
With linearly increasing molecular weight
Wear properties of UHMWPE
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Problems with UHMWPE in the application of
artificial joints- wear particle produced at
sliding surfaces- accelerates the loosening
Wear particles
Formation of particles
with diameter < than 1 micron
Schematic illustration of an artificial hip joint
Solution: Use of transfer film
Lubrication; a very thin film of
Polymer is transferred to the
Opposing surface, lead to the
Resultant coefficient of friction
Being very low
New processing of UHMWPE
To obtain high performance implants-alter the
properties of UHMWPE
1)
Increased the crystallinity (without causing
degradation)- by using temperature greater than
250C and pressure greter than 2,800 atm.obtained crystallinity over 80%
2)
Crosslinking UHMWPE by low-dose γ-ray
sterilization in a vacum or inert gas, then stored in
oxygen free environment or heat-treated at temp.
below the melting point in a vacuun or inert gas
3)
Addition of vitamin E- prevent the crack formation
BONE CEMENT
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Acrylic cement is used for the fixation of total
joint prosthesis
The cements used in orthopedic surgery are
combination of prepolymerized PMMA solid
particle and the liquid monomer
The powder particles are sphere (30 to 150
µm in diameter), molecular weight of 20,000
to 2 million
For the reaction to occur,prepolymerized
PMMA needs to contain an initiator, dibenzoyl
perioxide (BP)
BONE CEMENT
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The liquid monomer contains the activator
N,N-dimethyl-p-toluidine (DMPT)
The monomer will polymerized on its own
when exposed to light or heat.
To prevent to monomer from polymerizing,
the liquid generally contain an inhibitor or
retardant, hydroquinone- function to absorb
free radical that may occur and initiating the
polymerization
Preparation of Bone Cement
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The prepolymerized + liquid monomer (mixed
together), chemical reaction begin with
activator (DMPT) and the initiator (BP)
combining and releasing a benzoyl peroxide
free radical, and react with the monomer.
Polymerization begin.
Chains with double bond converted to single
bond, heat is generated as an exotherm, and
the cement cure
Problems of PMMA Bone Cement
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3)
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Strong exothermic setting reaction
Toxic effect of the monomer
Inability to bond directly to bone - caused
loosening at the interface
Brittle nature
- To overcome these problems, many types of
bioactive bone cements have been
developed.
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To improve the biochemical properties of
PMMA bone cement, many types of bioactive
particle fillers have been added into the
cement
Example of particle fillers are glass ceramic,
titania (anatase & rutile), etc
Recent studies on Bone Cement + titania particles
(K. Goto et al., Biomaterials 26 (2005))
Figure (c)
Shows direct
Contact
Between bone (B)
And Cement (C),
while Figure (b)
Shows soft
Tissue layer
Less than
10 um. The soft
Tissue layer
In (a) and (d)
Is thicker
Than (b) and (c)
2. Bioabsorbable Polymers for
surgical applications
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Polymeric materials and composites have been
used in medical applications; tissue
replacement, support of tissues and delivery of
drugs
Based on their behavior in living tissue,
polymeric biomaterials can be divided into;
1)Biostable
2) Bioabsorbable (biodegradable/bioresorbable)
Biostable Polymers
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Are inert
Cause minimal response in surrounding
tissue
Retain their properties for years
Example: polyethylene, polypropylene; used
for endoprostheses and sutures
Bioabsorbable (biodegradable/bioresorbable)
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Temporary internal fixation, can be partially
and fully bioabsorbable material
Bioabsorbable implant preserve the structure
of tissue at the early stage of the healing,
example in bone, tendon and tissue
After that, the implant decomposes, and
stress are gradually transferred to the healing
tissue
Bioabsorption of the materials induced by the
metabolism of the organism
Bioabsorbable
(biodegradable/bioresorbable)
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a)
b)
c)
d)
Bioabsorbable surgical devices need no
removal
Requirements for bioabsorbable materials;
noncarcinogenic, tissue compatible,
nontoxic, etc
Should not cause morbidity
Must provide adequate mechanical strength
and stiffness
Degradation should occur by hydrolysis in
aqueous media
Bioabsorbable Polymers for surgical
applications
1)
Suture Materials
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Polyglycolid acid (PGA) and Polylactic acid
(PLA) have been used as synthetic
bioabsorbable sutures
Bioabsorbable sutures are used in the
fixation of bone fractures,closure of soft
tissue wound, etc
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A Typical Suture Line
Polyglycolid Acid (PGA) and Polylactic
(PLA)
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PGA - High molecular weight, hard, tough
crystalline polymer, Tm at about 224-226ºC,
Tg of 36ºC.
PLA – Tm of 174-184ºC, Tg of 57ºC.
Such polymers can be processed into fibers,
films, rods, screws, plates, clamps, etc
Advantages of polymeric materials compared
to metal and ceramics; easy and cheap to
make
Bioabsorbable Polymers for surgical
applications
2) Porous Composites
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Combining bioabsorbable polymers in porous
and nonporous materials
Hydroxyapatite powders and blocks have
applications in the bone surgery, e.g. to fill
the defects
Since porous ceramics are brittle, the
toughness has been increased by combining
them with polymers
Bioabsorbable Polymers for surgical
applications
3) Drug Delivery System
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Polymeric devices for the controlled release
of drugs and antibiotic have been studied
These polymers show several advantages
over traditional repeated dosage methods
This technique can save patients from being
exposed to greater amounts of drug at the
desired site of action
Bioabsorbable Polymers for surgical
applications
4) Partially Bioabsorbable Device
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The reinforcement of bioabsorbable
polymeric matrices with biostable fibers
produce strong, partially bioabsorbable
materials
Example; PLA matrix reinforced with carbon
fiber, copolymer MMA and N-vinylpyrrolidone
reinforced polyamide fibers, etc used for
ligaments, tendon, scaffolds, etc.
Example of Bioabsorbable materials in artificial skin
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Skin damage following severe burns or ulcers, such
as diabetic foot ulcers, is notoriously difficult to heal.
This is because the dermis cells will not regenerate
in the absence of a matrix on which to grow
Recently the development of tissue engineering
and, in particular, artificial skin has presented
advances in this area
These artificial skins (keratinocyte seeded
IntegraTM, DermagraftTM, and ApligraftTM which
contain neonatal cells in combination with matrices
formed from bovine collagen or the soluble suture
materials polylactic and polyglycolic acids) provide a
matrix for dermis growth and the neonatal cells
contained in them produce growth factors which
promote healing
3. Adhesives for medical applications
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The use of surgical tissue adhesives in
medicine has developed over 40 years
Traditionally, the area of tissue reattachment
or repair following surgery has been
dominated by sutures, staples and wiring
Recently, there is a huge potential for tissue
adhesives in clinical practice
Pressure Sensitive Adhesives (PSAs)
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PSAs have been used for adhering wound
dressing to skin
PSAs have Tg in the range of -20 to -60ºC,
which means they are soft materials at room
temp.
These soft polymers are able to flow and wet
out on to a surface and are able to adherence
to that surface
Pressure Sensitive Adhesives (PSAs)
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The bond formed between PSA and substrate
is not permenant and can be broken with a
measurable force
Mid-19th century, the first adhesive plasters
were used, the first aid application of
dressing become more demanding, and
undergone significant development
Early adhesive formulations were based on
blends of natural rubber and resin.
Now PSAs were dominated by acrylic
copolymer
Requirement for PSAs
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Should be permanently and aggressively
tacky, adhere with only slight finger
pressure
Form a strong bond with surfaces
Sufficient cohesiveness that it can be
removed without leaving a residue
Need to be chemically and biologically
accepted to the skin-no irritation or
sensitization
Requirement for PSAs
5) Adhesives must have sufficient flow to
ensure intimate surface contact
6) Must be able to cope with moisture at the
skin without compromising performance
7) PSAs should be easily removed with minimal
trauma to the skin
Example of First Aid Dressing
Adhesive Types
Acrylic Polymer
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Widely used due to natural adhesive behavior
and wide scope of formulation/property
tailoring
PSAs are typically copolymer composed of
‘hard’ monomer and ‘soft’ monomer
The Tg of the resultant polymer can be
controlled by the ratio of hard and soft
monomers
The nature of alkyl group, R’, can be used to
dictate the adhesives properties, by varying the
chain length and hydrophilic/hydrophobic nature
of the group
Chain length
Rubber-Based PSAs
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Early medical adhesives were based on
natural rubber
Now changed to synthetic elastomers such
as polyisoprene and polyisobutylene
Polyisobutylene tend to pack tightly, results in
low air and moisture permeability
The low Tg of these materials produce
flexible material, that are naturally tacky,
allowing the polymer to wet out the skin
surface
Silicones
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- Used since mid 1960, have been utilized for
tapes, dressing, bandages
Typically formulated from silicone resins and
polydimethyl siloxane gum
To impart cohesive strength, the polymer and
resin are crosslink to form a network
The properties of the final adhesives can be
controlled by ratio of component and the
cross-link density
Types of Transdermal Drug Delivery Designs
More recently, silicone adhesives were used in
transdermal drug delivery system-controlled entry of
pharmaceutical into the blood
Delivery of an active ingredient through the skin and
into the blood vessels before delivery into the target organ