Failure Analysis

1. Drug Eluting Coronary Stent Coatings
Part 10: Drug Eluting Heart Stent Coatings

2. Copyright ©1996 American Heart Association
Edelman, E. R. et al. Circulation 1996;94:1199-1202
Angioplasty and Stenting are Competitive Procedures
Divergent processes of vascular repair after balloon angioplasty
and stenting of an atherosclerotic vessel

3. Divergent processes of vascular repair after balloon angioplasty and
stenting of an atherosclerotic vessel. Balloon angioplasty (top) compresses
and fractures the atherosclerotic plaque (light gray) and tunica media
(black), slightly enlarging the artery. After a few days, a thin layer of
platelet-rich thrombus (dark gray) lines the lumen and fills the dissection
plane. The lumen shrinks from combined effects of early elastic recoil and
later formation of a fibrocellular neointima (speckled area). Stent
deployment after angioplasty (bottom) compresses the dissection plane
and enlarges the lumen while stretching the artery with minimal elastic
recoil. Within hours to days after stenting, caps of thrombus infiltrated with
inflammatory cells (dark gray) form over stent struts (black rectangles),
particularly abundant at sites of deep injury. Over ensuing weeks, a
neointima forms (speckled area), thicker where injury is more severe.
Although intimal growth after stenting is greater than after balloon
angioplasty, the residual lumen is also larger, as the scaffolding of the stent
maintains luminal dimensions. Late changes in arterial size are not depicted
because the contribution of remodeling to restenosis after angioplasty or
stenting remains incompletely characterized.
(Figure prepared by James Squire.)
Edelman, E. R. et al. Circulation 1996;94:1199-1202

4. Stents scrape blood vessel walls. This injury causes reblockage.
Edelman and Squire

5. Stents scrape blood vessel walls
Edelman and Squire

6. Drug Eluting Coated Stent
3.0mm X 2.3mm

7. 420μ X 550μ 300μ X 390μ
Drug Eluting Coated Stent

8. Drug Eluting Coated Stent
420μ X 550μ 300μ X 390μ

9. A Different Manufacturer’s
Drug Eluting Coated Stent
3.0mm X 2.3mm

10. 420μ X 550μ 300μ X 390μ
A Different Manufacturer’s
Drug Eluting Coated Stent

11. IR Spectrum of PC 1036 from Biomaterials 21 (2000) 1847-1859
Phosphatidyl Choline (PC)
coating, invented by
Biocompatibles, Ltd., used
on some Medtronic and
Abbott Drug Eluting
Coronary Stents.
Spectra of coatings obtained
off the actual stent surfaces
show the PC coating and the
anti-restenosis drug it elutes.
All drug was extracted from
the Abbott stent but PC
coating remains.

12. IR Spectra of pure PC, PC 1036, Medtronic Stent Coating, and
Abbott Stent Coating
 The Pure PC’s IR shows most of the vibrations present in the PC 1036 coating.
 The PC 1036 IR was published back when Biocompatibles, Ltd. was trying to
“drum up” big company interest in their materials. [This particular spectrum is
slightly distorted (an “enlarged” 1090 vibration) because it is a surface spectrum
(obtained via ATR) of a PC polymer in which the hydrophilic PC moieties have
been rotated preferentially to the surface by contact with water. The 1090 is the
C-O-P stretching vibration.]
 The Medtronic (Endeavor™) and Abbott (BiodivYsio™) stent coating spectra
were obtained by reflection off the stents’ surfaces.
 The stent coatings are excellent matches to the spectrum of PC 1036. Since this
is the coating Biocompatibles, Ltd. developed for the BiodivYsio stent, I believe
it is the PC coating on the Medtronic and Abbott stents. EDAX can be run using
the SEM to see if silicon is detected from the PC 1036 TSMA component. The
literature published by Biocompatibles, Ltd. suggests a TSMA content of 3 to 5%.
At this loading EDAX should detect the silicon.

13. Biocompatibles, Ltd. developed the PC-coated
BiodivYsio™ stent and marketed a number of PC
polymers. One of these polymers, PC1036, appears
to be the PC coating on the BiodivYsio stent,
now a product of Abbott. It also appears to be
the coating Abbott has licensed to Medtronic for
the Endeavor stent.
PC 1036 is made using the four acrylic monomers
shown here.
>2-methacryloyloxyethyl phosphorylcholine (MPC)
>lauryl methacrylate (LMA)
>hydroxypropyl methacrylate (HPMA)
>3-trimethoxysilylpropyl methacrylate (TSMA)
MPC supplies the PC functionality to the polymer.
LMA helps the polymer adhere to metal surfaces.
TSMA makes the polymer crosslinkable, which
improves its adhesion and cohesion and helps control
its rate of drug elution.
HPMA is a co-crosslinker that, used with TSMA at 25%
loading, gave good mechanical properties.
AIBN (azoisobutyronitrile) initiates polymerization.
PC 1036 Biocompatibles, Ltd.
Biocompatibles, Ltd. paper

14. TSMA Hydrolysis initiates the Crosslinking of the Coating
The Drug Elution Rate is determined mainly by the extent of crosslinking.
The hydroxy groups of the HPMA moiety will crosslink with TSMA also.
Biocompatibles, Ltd. paper