Coatings, Surface Modifications,
and Bio-Absorbables
John Wainwright, Ph.D.
Sr. R&D Manager, Medtronic plc
Some of the technologies/devices discussed in this talk are not approved in the US
WLNC 06/08/15
Reasons for Coatings and
Surface Modifications


Lubricious coatings

Hydrophobic

Hydrophilic
Corrosion Resistance

Material Choice



Stainless steel, CoCr, NiTi

Passivation

Electropolish

Parylene coating
Lower material thrombogenicity

Electropolishing

Silicon Carbide

Heparin

Phosphoryl Choline
Bio-Absorbable stents
Lubricious Coatings

Extremely dependent on processing conditions including:



cleaning, activation/base coat, coating, curing
Testing:

Water droplet contact angle for hydrophilicity

Friction for lubricity and durability

Particulate testing for durability/device interactions
Hydrophobic

PTFE (fluoropolymers): longest use


Inert but higher friction than PVP and HA
Hydrophilic
Hydroscopic (swell in fluid)
 PVP (polyvinylpyrrolidone): Most common hydrophilic



PVP particles from Cook Shuttle/Slip-Cath has been
associated with intraparenchymal hemorrhage in 3 patients
(Hu et al 2014)
HA (hyaluronic acid): more lubricious/biocompatible, but
less stable
Corrosion Resistance



Material Choice

Stainless steel, CoCr, Nitinol

CoCr more corrosion resistant without post processing due to
composition
Higher Breakdown Potential (Ebd)= more corrosion resistant
Niti corrosion resistance (Trepanier 97)

PA=Passivated

EP= Electropolished

HT= Heat treated

AA= electropolished and then heat treated

NT= non-treated
Parylene coating- polymer coating applied through vapor deposition
often applied for corrosion resistance

Enterprise™ device is covered with a thin layer of Parylene
(Heller 2011)

“Lubricious Coating Our proprietary stent coating may facilitate stent tracking
through the microcatheter.” (Codman marketing brochure)
Lower material thrombogenicity




Electropolishing

EP NiTi has shown to absorb less platelets and plasma than stainless
steel (Thierry 2002)

Inert titanium oxide surface
Silicon Carbide

Chemically inert, corrosion resistant, and may reduce thombogenicity
(Harder et al 99)

PHAROS Viteese ICAD stent and Rithron coronary stent
PhosphorylCholine (PC)

PC is naturally abundant on the surface of red blood cells1-10

Coating or treating a device surface with a PC-containing polymer
results in physiologic mimicry of the cell membrane
Heparin

Actively prevents thrombus formation so could affect aneurysm occlusion

BX VELOCITY stent with HEPACOAT and aspirin alone after the procedure
was safe in select patients with de novo or restenotic lesions in native
coronary arteries. (Mehran 2003)

Carmeda® heparin coating covalently bonded to surface

May be regulated as a drug/combination product
PC Surface Modification vs. Coating
Method
Adhesion to
Substrate
Thickness
Process
Shield Technology™
Surface Modification
“Standard” PC Coating*
Catheter or Stent
Covalent Chemical
Bonding
Encapsulation
< 3 nanometer
(one braid wire=25400 nm)
500-4000 nanometer
Chemical Reaction
Dipping, Spray or Brush
SEM Images
Bare Braid
Shield Technology™
Early Development
Work
*Note: Standard PC Coatings are similar to EVAHEART LVAD (ClinicalTrials.gov Identifier:
NCT01187368), Endeavor (P060033) and BiodivYsio Stents (P000011)
Early Development
Work
Early Development
Ways to evaluate thrombogenicity
Method
Pro
aPTT (partial • Standard biocompatiblity
and clinical test
thrombo
plastin time)
Blood flow
loop testing
•
Animal models:
•
Porcine
Rabbit
•
Con
• Not sensitive enough to detect
differences
• ~5% of thrombin is formed for
clot time
• Large blood sample to sample
variation
Visually stimulating results • Limited number of samples per
run
• Large blood sample to sample
variation
• Variation within test run
Difficult to titrate thrombogenic response. Safety Only
Multiple devices per animal • More pronounced
endothelialization
• More spasm
Possibly more correlative
• Slower to endothelialize
aneurysm occlusion
• Elastase model has high
morbidity, expensive, no internal
controls
Material Thrombogram Testing
•
Quantitative, Repeatable, Validated,
method used clinically11-15
•
Uses human platelets and
plasma
•
Compare Peak Thrombin (nM)
•
More sensitive to differences
than aPTT (industry standard)
Girdhar et al 2015
Testing Performed by Dr. Wayne Chandler, Director of Coagulation Laboratory
Houston Methodist Hospital
Girdhar et al 2015
Bench Test results may not necessarily be indicative of clinical performance
Reduced Material Thrombogenicity
Shield Technology™
only affects
Surface Activation
• Intimal damage
• Device material
Virchow’s
Triad of
Thrombosis
Flow Disruption
• Wall apposition
• Stent design
Bench Test results may not necessarily be indicative of clinical performance
Hypercoagulable
• Anti-platelet
non-responder
• HIT
• Other
Bio-Absorable Stents

Abbott BVS most researched absorbable stent (ABSORB study)

Thicker stent struts


More issues with malapposition and overexpansion than
metal stents


Harder for delivery
7% malapposition
Rate of absorption varies

~2 yrs for Abbott Absorb BVS
http://www.cathlabdigest.com/articles/Bioabsorbable-Stents-%E2%80%93-Where-Are-We-Now
Future of innovation

Access and delivery systems: more lubricious and durable
coatings

Flow Diverters and AB Stents: lower thrombogenic and
enhanced endothelialization without perforator
complications


Intrasacular devices:???
Intracranial artery stenosis: address major complications
of stroke and hemorrhage
References
1.
Lewis, A.L. and P.W. Stratford, Phosphorylcholine-coated stents. J Long Term Eff Med Implants, 2002. 12(4): p. 231-50.
2.
Lewis, A.L., et al., Crosslinkable coatings from phosphorylcholine-based polymers. Biomaterials, 2001. 22(2): p. 99-111.
3.
Whelan, D.M., et al., Biocompatibility of phosphorylcholine coated stents in normal porcine coronary arteries. Heart,
2000. 83(3): p. 338-45.
4.
Kuiper, K.K., et al., Phosphorylcholine-coated metallic stents in rabbit iliac and porcine coronary arteries. Scand
Cardiovasc J, 1998. 32(5): p. 261-8.
5.
Chen, C., et al., Phosphorylcholine coating of ePTFE grafts reduces neointimal hyperplasia in canine model. Ann Vasc
Surg, 1997. 11(1): p. 74-9.
6.
Zheng, H. et al. Clinical experience with a new biocompatible phosphorylcholine-coated coronary stent. The Journal of
invasive cardiology 11, 608-614 (1999).
7.
Galli, M. et al. Italian BiodivYsio open registry (BiodivYsio PC-coated stent): study of clinical outcomes of the implant of
a PC-coated coronary stent. The Journal of invasive cardiology 12, 452-458 (2000).
8.
Grenadier, E. et al. Stenting very small coronary narrowings (< 2 mm) using the biocompatible phosphorylcholine-coated
coronary stent. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac
Angiography & Interventions 55, 303-308 (2002).
9.
Boland, J. L. et al. Multicenter evaluation of the phosphorylcholine-coated biodivYsio stent in short de novo coronary
lesions: The SOPHOS study. International journal of cardiovascular interventions 3, 215-225,
doi:10.1080/14628840050515966 (2000).
10.
Beaudry, Y., Sze, S., Fagih, B., Constance, C. & Kwee, R. Six-month results of small vessel stenting (2.0-2.8 mm) with
the Biodivysio SV stent. The Journal of invasive cardiology 13, 628-631 (2001).
11.
Chandler, Wayne, and Roshal, Mikhail, Optimization of Plasma Fluorogenic Thrombin-Generation Assays, Am J Clin
Pathol 2009; 132:169-179.
12.
Gerotziafas, et al., Towards a standardization of thrombin generation assessment: The influence of tissue factor,
platelets and phospholipids concentration on the normal values of Thrombogram-Thrombinoscope assay, Thrombosis
Journal 2005, 3:16.
13.
Hemker, et al., Calibrated Automated Thrombin Generation Measurement in Clotting Plasma, Pathophysiol Haemost
Thromb 2003; 33:4-15.
14.
Spronk, et al., Assessment of thrombin generation II: Validation of the Calibrated Automated Thrombogram in plateletpoor plasma in a clinical laboratory, Thromb Haemost 2008; 100:362-364.
15.
Tepe, G., et al., Thrombogenicity of Various Endovascular Stent Types: An In Vitro Evaluation. Journal of Vascular and
Interventional Radiology, 2002. 13(10): p. 1029-1035.