Transcript POLYMERS

Polymer Biomaterials
There are a large number of uses for polymers in the biomaterials
field. These arise due to the wide variety of properties possible.
OBJECTIVES
 to introduce some fundamental polymer properties and the
factors that influence them
 to provide an overview of the uses of polymers as
biomaterials
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POLYMERS
Polymers - long chain molecules of high molecular weight
-(CH2)nUse
State
n
1-4
gas
burned for energy
5-11
liquid
gasoline
9-16
med. visc.
liquid
kerosene
16-25
hi visc. liq.
oil, grease
25-50
solid
paraffin wax
10003000
tough plastic PE bottles, containers
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Common Polymer Biomaterials
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Polymers In Specific Applications
application
properties and design requirements
polymers used
dental
•stability and corrosion resistance, plasticity
•strength and fatigue resistance, coating activity
•good adhesion/integration with tissue
•low allergenicity
PMMA-based resins for
fillings/prosthesis
polyamides
poly(Zn acrylates)
ophthalmic
•gel or film forming ability, hydrophilicity
•oxygen permeability
polyacrylamide gels
PHEMA and copolymers
orthopedic
•strength and resistance to mechanical restraints and
fatigue
•good integration with bones and muscles
PE, PMMA
PL, PG, PLG
cardiovascular
•fatigue resistance, lubricity, sterilizability
•lack of thrombus, emboli formation
•lack of chronic inflammatory response
silicones, Teflon,
poly(urethanes), PEO
drug delivery
•appropriate drug release profile
•compatibility with drug, biodegradability
PLG, EVA, silicones,
HEMA, PCPP-SA
sutures
•good tensile strength, strength retention
•flexibility, knot retention, low tissue drag
silk, catgut, PLG, PTMC-G
PP, nylon,PB-TE
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Properties: Molecular weight
synthetic polymers possess a molecular weight distribution
Ni
Mi
åN M
=
åN M
i
Mw
2
i
i
i
åN M
=
åN
i
i
Mn
i
i
i
dispersity index = Mw/Mn
i
i
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The Bulk State : Solid
Polymers can be either amorphous or semi-crystalline, or can exist
in a glassy state.
amorphous glassy state
 hard, brittle
 no melting point
semi-crystalline glassy state
 hard, brittle
 crystal formation when cooled
 exhibit a melting point
Glass transition temperature (Tg)
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Thermal Behavior
semi-crystalline
Rubber
Liquid
Viscous
Liquid
Tm
tough plastic
T
Tg
semi-crystalline plastic
crystalline solid
10
1000
100000
1000000
molecular weight (g/mol)
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Crosslinked Networks
crosslinks
 covalent; H-bonding; entanglements
crosslinking
 increased molecular weight
 swell in solvents
• organogel
• hydrogel
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Thermal Properties
Polymer
Tg (ºC)
Tm (ºC)
Nylon 6,6
45
267
UHMWPE
-125
140
Silicone
-123
-29
poly(urethane)
0-90
125-225
poly(methylmethacrylate)
105
160
poly(D,L-lactide)
50
amorphous
poly(-caprolactone)
- 60
57
poly(glycolic acid)
35
210
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Viscoelasticity
Stress
The response of polymeric materials to an imposed stress may under
certain conditions resemble the behavior of a solid or a liquid.
Strain
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Mechanical Properties
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Diffusion in Polymers
Polymers can also act as solvents for low molecular weight
compounds. The diffusion of small molecular weight components
in polymers is important in a number of fields :





purification of gases by membrane separation
dialysis
prevention of moisture loss in food and drugs (packaging)
controlled drug delivery (transdermal patches, Ocusert)
polymer degradation
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Diffusion in Polymers
Flux is dependent on :
 solubility of component in polymer
 diffusivity of component in polymer
These in turn depend on :
 nature of polymer
 temperature
 nature of component
 interaction of component with polymer
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Solubility Estimation
From Hildebrand, the interaction parameter, c, is defined as :
V1(d1 - d 2 )
c=
RT
2
The solubility parameter, d, reflects the cohesive energy density of a
material, or the energy of vapourization per unit volume.
While a precise prediction of solubility requires an exact knowledge of the
Gibbs energy of mixing, solubility parameters are frequently used as a
rough estimator.
In general, a polymer will dissolve a given solute if the absolute value of
the difference in d between the materials is less than 1 (cal/cm3)1/2.
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Diffusivity
experimental observations
 effect of T vs Tg
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Diffusivity
effect of permeant size
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Diffusivity : Effect of Crystallinity
solutes
 do not penetrate crystals readily
 take path of least resistance
• through amorphous regions
 increased path length
D1,c
æ 1-f ö
= D1,a ç f c ÷
ç 1+ c ÷
è
xø
D1,c = diffusivity in semi-crystalline polymer
D1,a = diffusivity in amorphous polymer
fc = volume fraction of crystals
x = shape factor (=2 for spheres)
(Mathematics of Diffusion)
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Example of Undesirable Absorption
 poppet-style heart valve
• poppet is composed of PDMS
• in small % of patients the poppet jammed or escaped
• recovered poppets were yellow, smelled, and had strut
grooves
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Leaching - Undesirable
 polymers often contain contaminants as a result of their
synthesis/manufacturing procedure/equipment
 may also contain plasticizers, antioxidants and so on
 these contaminants are a frequent cause of a polymer’s
observed incompatibility
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Drug Delivery
Ocusert
TD - Scopolamine
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In Vivo Degradation of Polymers
 no polymer is impervious to chemical and physical actions of
the body
Mechanisms causing degradation
Physical
Chemical
sorption/swelling hydrolysis
softening
oxidation
dissolution
enzymatic
stress cracking
fatigue cracking
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Hydrolytic Degradation
hydrolysis
 the scission of chemical functional groups by reaction with
water
there are a variety of hydrolyzable polymeric materials:
esters
amides
anhydrides
carbonates
urethanes
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Hydrolytic Degradation
degradation rate dependent on
 hydrophobicity
 crystallinity
 Tg
 impurities
 initial molecular weight, polydispersity
 degree of crosslinking
 manufacturing procedure
 geometry
 site of implantation
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Hydrolytic Degradation
bulk erosion (homogeneous)
 uniform degradation throughout polymer
process
 random hydrolytic cleavage (auto-catalytic)
 diffusion of oligomers and fragmentation of device
surface erosion (heterogeneous)
 polymer degrades only at polymer-water interface
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Polyesters
fractional change in molecular weight
Polyesters
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Oxidative Degradation
usually involves the abstraction of an H to yield an ion or a radical
 direct oxidation by host and/or device
• release of superoxide anion and hydrogen peroxide by
neutrophils and macrophages
• catalyzed by presence of metal ions from corrosion
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Poly(Carbonates)
PEC in vivo
M. Acemoglu, In. J. Pharm.
277 (2004) 133-139
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Enzymatic Degradation
Natural polymers degrade primarily via enzyme action
 collagen by collagenases, lysozyme
 glycosaminoglycans by hyaluronidase, lysozyme
There is also evidence that degradation of synthetic polymers is
due to or enhanced by enzymes.
Z Gan et al., Polymer 40 (1999) 2859
C.G. Pitt et al.,
J. Control. Rel. 1(1984) 3-14
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