Biocompatibility of Stent Materials

1
Biocompatibilityof Stent Materials

• issel lim
• BEH.105
• Production Crew
• 4.15.2003

2
Overview

• Introduction to biocompatibility
• Current options
• Polymeric possibilities
• Future research
• Questions

3
Overview

• Introduction to biocompatibility
• Current options
• Polymeric possibilities
• Future research
• Questions

4
Introduction to biocompatibility

• Introduction to biocompatibility
• what is it?
• host response to an implant
• testing for biocompatibility
• avoiding complications

5
introduction to biocompatibility
(continued)

• What is Biocompatibility?
• the ability of a material to perform with an
  appropriate host response in a specific
  application.
• therefore
• General definition

A material is considered biocompatible if it
allows the body to function without complications
like allergic reactions or adverse side effects.
Biocompatibility is the suitability of a
material for exposure to the body or bodily
fluids.
http//www.mse.cornell.edu/courses/engri119/Class_
Notes/E119_9p.PDF http//www.sma-inc.com/glossary.
html
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introduction to biocompatibility
(continued)

• Host response to an implant
• trauma a wound _at_ the implant site
• inflammation reddening, swelling, heating, pain
• Exudation
• Phase I acute inflammation
• Phase II chronic inflammation
• implant covered w/ macrophages
• healing scarring

An implant is biocompatible if the body undergoes
the normal healing process after surgery.
http//www.mse.cornell.edu/courses/engri119/Class_
Notes/E119_9p.PDF
7
introduction to biocompatibility
(continued)

• When lacking biocompatiblity
• long-lasting chronic inflammation
• cytotoxic chemicals
• disruption of cells _at_ interface
• micron-sized materials
• irritation
• corrosion of metals
• restenosis/thrombosis

To guard against complications in patients, test
the material in vitro, then in vivo.
http//www.mse.cornell.edu/courses/engri119/Class_
Notes/E119_9p.PDF
8
introduction to biocompatibility
(continued)

• Testing
• in vitro
• Direct contact
• Agar diffusion
• Elution
• in vivo
• Porcine models cardiovascular disease
• Dogs/Sheep bones
• Guinea Pigs subcutaneous

In vitro tests measure cytotoxicity. In vivo
tests measure effectiveness.
Ratner, p. 216 - 221
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introduction to biocompatibility
(continued)

• Solutions
• inert
• a biocompatible stent
• Must not evoke inflammatory reaction
• Must provide sufficient initial support to oppose
  the retracting force exerted by the diseased
  vessel

• what materials best perform these functions?

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Overview

• Introduction to biocompatibility
• Current options
• Polymeric possibilities
• Future research
• Questions

11
Current options
H C Tan, Y T Lim http//www.sma.org.sg/smj/4006/ar
ticles/4006me2.html
12
current options
(continued)

• Metals
• Stainless steel (namely 316L steel)
• Gold
• Cobalt-Chromium alloys
• Titanium
• Tantalum
• Nitinol

H C Tan, Y T Lim http//www.sma.org.sg/smj/4006/ar
ticles/4006me2.html
13
current options
(continued)

• Metals
• Stainless steel (namely 316L steel)
• Gold
• Cobalt-Chromium alloys
• Titanium
• Tantalum
• Nitinol

What were trying to avoid restenosis,
likelihood of corrosion, thrombosis, arrhythmias,
allergic reactions, myocardial infarction,
stroke, bleeding complications, hemorrhage, death
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current options
(continued)

• Positives
• radio-opaque
• flexible
• Negatives
• more brittle than stainless steel
• Current Examples

• Tantalum Cordis Stent a single tantalum filament
  wound into a helix, deployed via an expandable
  delivery balloon
• - Wiktor Stent (Medtronic) 15mm-long stent w/ a
  single tantalum wire wrapped around a PTCA balloon

http//biomed.brown.edu/courses/bi108/BI108_1999_G
roups/Stents_Team/balloon.htm
15
current options
(continued)

• Biocompatibility
• Current Examples
• Tantalum Cordis Stent
• 147 stents in 105 patients from Sept 1995 March
  1996
• 3 patients with thrombosis,
• 26 restenosis, 14.5 repeat revascularization
• Wiktor Medtronic
• 93 stents implanted
• Stenosis 0 /- 10
• Collapsed gradually (as opposed to rapidly) upon
  application of a threshold force

In short, tantalum is a great metal for viewing
and supporting, but there ARE more biocompatible
options out there.
http//biomed.brown.edu/courses/bi108/BI108_1999_G
roups/Stents_Team/balloon.htm
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current options
(continued)

• Nickel Titanium Naval Ordinance Laboratory
• 55 Nickel and 45 Titantium
• Shape-memory alloy
• Super-elasticity

Has the ability to return to a specific shape
upon heating to a certain temperature after its
phase transformation
Springy, rubberlike behavior present in NiTi
shape memory alloys at the temperatures of its
Austenite phase
http//www.imagesco.com/catalog/nitinol/nitinol.ht
ml
17
current options
(continued)

• Shape memory / Superelasticity
• Austensite higher temperature phase present in
  NiTi
• Martensite lower temperature phase present in
  NiTi

In the martensitic form, the alloy can be easily
deformed to a new shape. However, when the alloy
is heated through its transformation
temperatures, it reverts to austenite and
recovers its previous shape.
Schematic of Shape-Memory Behavior
http//www.sma-inc.com/SMAandSE.html
18
current options
(continued)

• Biocompatibility
• in vitro human osteoblast and fibroblast cell
  cultures
• Compared w/ stainless steel and pure titanium
• NiTi higher initial nickel dissolution, but no
  toxic effects, no decrease in cell proliferation,
  no inhibition in cell growth upon direct contact
• in vivo stent implantation in rats for 26 weeks
• Compared with stainless steel and Ti-6Al-4V alloy
• Muscular tissue, neural, and perineural responses
  non-toxic and non-irritating

The biocompatibility of NiTi seems to be similar
to or better than that of stainless steel or
Ti-6Al-4V alloy.
http//www.sma-inc.com/SMAandSE.html
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Overview

• Introduction to biocompatibility
• Current options
• Polymeric possibilities
• Future research
• Questions

20
Polymeric possibilities

• Polymers
• Plastic stents
• Shape-memory polymers
• Biodegradable polymers
• biodegradable vs. bioabsorbable

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polymeric possibilities
(continued)

• Silicone
• first material chosen for stents
• Generic condensation polymer derived from
  alternating silicone and oxygen atoms
• Plastic stents (biliary stents)
• polyethylene
• polyurethane

Silicone and these plastics provide organic
alternatives for stents, but there Must be
something better out there
http//www.bostonscientific.com/common_templates/a
rticleDisplayTemplate.jhtml?tasktskMedArticleOver
view.jhtmlsectionId4relId8,386,387,388,389,390
deviceId134uniqueIdMPAO541
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polymeric possibilities
(continued)

• Biodegradable polymers
• biodegradable vs. bioabsorbable
• Ideal polymer characteristics
• Factors that accelerate polymer degradation

Biodegradable polymers these devices usually
serve only temporary purposes in the body
Ratner, p. 66 http//www.devicelink.com/mpb/archi
ve/98/03/2002.html
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polymeric possibilities
(continued)

• Biodegradable Polymers

A biodegradable intravascular stent prototype is
molded from a blend of polylactide and
trimethylene carbonate. Photo Cordis Corp.
Prototype Molded by Tesco Associates, Inc.
http//www.devicelink.com/mpb/archive/98/03/002.ht
ml
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polymeric possibilities
(continued)

• Biodegradable polymers
• Specific polymers
• Polyglycolide (PGA)
• Poly(e-caprolactone)
• Poly(dioxanone)(a polyether-ester)
• Poly(lactide-co-glycolide)

Biodegradable polymers synthesizing polymers
that have hydrolytically unstable linkages in the
backbone
Ratner, p. 66 http//www.devicelink.com/mpb/archi
ve/98/03/2002.html
25
polymeric possibilities
(continued)

• Biodegradable polymers
• biodegradable vs. bioabsorbable
• Ideal polymer characteristics
• Factors that accelerate polymer degradation

Biodegradable polymers these devices usually
serve only temporary purposes in the body
Ratner, p. 66 http//www.devicelink.com/mpb/archi
ve/98/03/2002.html
26
polymeric possibilities
(continued)

• Shape-memory polymers
• Designed by Dr. Andreas Lendlein and Dr. Robert
  Langer
• Ability to memorize a permanent shape, which
  can significantly differ from their permanent
  shape
• Reversible process

Exposure to a suitable stimulus causes the
transition of the materials from their temporary
to their permanent shape.
http//www.mnemoscience.com
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Overview

• Introduction to biocompatibility
• Current options
• Polymeric possibilities
• Conclusion
• Future Research
• References
• Questions

28
Conclusions

• Biocompatibility
• Biocompatibility is the suitability of a
  material for exposure to the body or bodily
  fluids.
• Current options
• Stainless steel, gold, cobalt-chromium alloys,
  titanium
• Tantalum, Nitinol
• Polymeric possibilities
• Current plastics, biodegradable stents,
  shape-memory polymers

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Future research

• Polymeric endoluminal paving
• Price list
• Clinical studies
• Most effective material

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References

• In alphabetical order
• Chem Soc. http//www.chemsoc.org/viselements/pages
  /tantalum.html
• Middleton, John C. and Arthur J. Tipton.
  Synthetic Biodegradable Polymers as Medical
  Devices. http//www.devicelink.com/mpb/archive/98
  /03/002.html
• Ratner, Buddy D., et al. Biomaterials Science An
  Introduction to Materials in Medicine. Academic
  Press San Diego, 1996.
• Tan, HC, and YT Lim. What you need to know
  Coronary Stenting Whats New in the Horizon?
  Singapore Medical Journal. Singapore Med J 1999
  Vol 40(06) http//www.sma.org.sg/smj/4006/article
  s/4006me2.html
• http//biomed.brown.edu/courses/bi108/BI108_1999_G
  roups/Stents_Team/balloon.htm
• http//www.imagesco.com/catalog/nitinol/nitinol.ht
  ml
• http//www.mnemoscience.com
• http//www.mse.cornell.edu/courses/engri119/Class_
  Notes/E119_9p.PDF
• http//pubs.acs.org/cen/topstory/7906/7906notw1.ht
  ml
• http//www.sma-inc.com/glossary.html
• http//www.sma-inc.com/SMAandSE.html
• http//www.vcs.ethz.ch/chemglobe/ptoe/_/73.html
  ChemGlobe. 2000.

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Biocompatibilityof Stent Materials
?

• issel lim
• BEH.105
• Production Crew
• 4.15.2003