Coronary Stents Design Part C – Biodegradable stents and Future Solutions

Dr. Amir Kraitzer

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Biodegradable Stents (BDS)

Rational for Biodegradable stents

Metal stent drawbacks Cause permanent physical

irritation Risk of long term endothelial

dysfunction and chronic inflammation

Metal have thrombogenic properties

Inability for the vessel to restore its a normal physiology

Biodegradable stent advantages May eliminate early and late

complications of bare-metal stents

Restore the vasoreactivity Allow a gradual transfer of the

mechanical load to the vessel Higher capacity for drug

incorporation and complex release kinetics

Facilitate re-intervention

The need for a permanent prosthesis decreases dramatically 6 months post-implantation

Design considerations Overall time and rate of degradation

a very rapid degradation rate can be associated with inflammation

Biocompatibility of degradation products to prevent toxicity

Mechanical properties Mechanical recoil Strut size Creep Embolization of degraded particles

Drug load Radiopacity

Igaki-Tamai BDS

A bioresorbable zigzag coil design PLLA (Initial MW=183KDa) Initial clinical trial results proved

efficacy and safety (2000) On November 2007 the stent

obtained CE mark indicated for peripheral artery

Igaki Tamai Stents loaded with ST638 (Tranilast) reduced neointima formation in animals

BVS (Abbott) Drug Eluting BDS

Drug: Everolimus Base Polymer: PLLA Coating: PDLLA Releases 80% of its drug in 28 days Maintains radial strength for 3

months Mass loss after 6 months, complete

resorption in two years Good clinical outcomes with two

years follow-up No occurrence of thrombosis

between 6 and 24 months

Source: Abbott Vascular, AP2929018Rev A

Stent Functionality phases

Richard J Rapoza, PhD presented at the ICI meeting of 2009, Tel Aviv, Israel

REVA Drug Eluting BDS

Drug: Paclitaxel Base polymer: Tyrosine-

derived polycarbonate platform Low recoil (<1%) Slide and lock design Tunable resorption rate Radiopacity is achieved by the

incorporation of iodine molecules

Absorbable Magnesium Stent (Medtronic) Radial strength and recoil

is similar to BMS 4-month clinical results: late

loss is comparable to BMS Further improvement in stent

design due to: Early recoil Fast degradation Neointima formation

BDS Summary

New Concepts

Pro-healing approach Drug eluting balloon

Endothelial Progenitor Cells Capture

Genous Stent

Precilinical trials 1 hour post- deployment:

90% cell coverage 1st Clinical trial

demonstrated safety and feasibility

2nd Clinical trial demonstrated late loss is comparable to BMS

Endothelial Progenitor Cell Capture by Stents Coated With Antibody Against CD34 : The HEALING-FIM Registry, Aoki et al, J. Am. Coll. Cardiol. 2005;45;1574-1579

Drug eluting balloon

Provides uniform drug dose Reduces thrombosis risk and

enables shorter dual anti-platelet regimen

Allows significantly lower drug dose compared with DES

Two forms of release Drug and spacer Nanoparticles

SeQuent® Please

Core/shell fiber structure concept

I. Good mechanical propertiesII. Effective drug release profileIII. Porous structured coating

allows controlled release

In-Vitro FTS Release

Porous coating

Porous coating

Dense coatingDense coating

Effect of coating’s porosity

50/50 PDLGA50/50 PDLGA 75/25 PDLGA75/25 PDLGA

References

Amir Kraitzer, Yoel Kloog, Meital Zilberman, Approaches for Prevention of Restenosis, J Biomed Mater Res Part B: Appl Biomater 85B: 583–603, 2008

Gladius Lewis, Review: Materials, Fluid Dynamics, and Solid Mechanics Aspects of Coronary Artery Stents: A State-of-the-Art Review, Biomed Mater Res Part B: Appl Biomater 86B: 569–590, 2008

Meital Zilberman, Amir Kraitzer, Orly Grinberg and Jonathan J. Elsner, Drug-Eluting Medical Implants, In : Handbook of European Pharmacology, 2008

Update on Bioabsorbable Stents: From Bench to Clinical, RON WAKSMAN, Journal of Interventional Cardiology, Vol. 19, No. 5, 2006

Thank you