The Emerging Paradigm of Stent Biocompatibility: Current Status and Future Directions Dr Miles Dalby Consultant Cardiologist Honorary Senior Lecturer Royal.

The Emerging Paradigm of Stent Biocompatibility: Current Status and Future Directions

Dr Miles DalbyConsultant CardiologistHonorary Senior LecturerRoyal Brompton & Harefield NHS TrustImperial College

Biotonik Speaker BureauConor Speaker BureauMSD Speaker BureauTranslumina Research GrantBoston Scientific Research FundingVolcano Research support

Conflicts of Interest

0.81.3

0.0

1.3 1.3

2.6

1.2

4.14.9

1.4

0

2

4

6

8

Late stentthrombosis

Thrombosis-related events

Cardiac death Non-fatal MI Death or MIEve

nts

bet

wee

n 6

-18

mo

nth

s (%

) BMS DES

0.81.3

0.0

1.3 1.3

2.6

1.2

4.14.9

1.4

0

2

4

6

8

Late stentthrombosis

Thrombosis-related events

Cardiac death Non-fatal MI Death or MIEve

nts

bet

wee

n 6

-18

mo

nth

s (%

) BMS DES

What makes a good stent…….

Acute performance: OK Anti-Restenotic Efficacy: OKSafety………………..n=????? t=?????

Evolution in Stent Biocompatibility

Coated Bare Metal Stent: Prokinetic

Drug Eluting Erodable Polymer Stent: Costar

Bioabsorbable stent: Magic

316L steel stent tube in fibrinogen solution with applied current via electrode (time wrapping 1:10)

Silicon Carbide and Thromboresistance

316LA-SiC:H

Silicon Carbide

Stainless Steel

0.5 µm

0.25 µm

0 µm

0.5 µm

0.25 µm

0 µm

Silicon Carbide and ThromboresistanceB

ioco

mpati

bili

ty

Silicon Carbide and Thromboresistance

Chandler loop

Silicon Carbide Stainless Steel

Silicon Carbide and Endothelialisation

Exposure of 316L and SiC to endothelial cells for 24h:

Light microscopy Atomic Force Microscopy

SiC

3

16L

Co-Star Paclitaxel eluting stent

Bridge Elements

Poly (lactide co-glycolide)

Bioresorbable polymer

Nanodroplet injection method Explant at 180 days

Costar architecture and apposition: OCT

Costar Stent Overlap: OCT

<100um

Costar:• Good acute performance (clinical experience and OCT)• Fully absorbable Polymer resulting in BMS• Platform for future drug release strategies

2 x 3mm 12 atm overlap no post dilatation

0

2

4

6

8

d3

0 M

AC

E (

%)

No Overlap Overlap

Costar IIBlind aggregate d30 MACE

Magnesium Alloy Bioabsorbable Stent

• Biocompatibility• Imaging• Re-Intervention• Surgery• ?Reduction in late thrombosis risk • Return of vascular function

PROGRESS AMS-1: FIM

% n % n % n

MACE 0 0 0 0 23.8 15

Death 0 0 0 0 0 0

Q-wave MI 0 0 0 0 0 0

Non Q wave MI 0 0 0 0 0 0

Ischemic Driven TLR

0 0 0 0 23.8 15

Primary Endpoint: Feasibility and safety at 4 months with MACE<30%. N=63

30-DayIn Hospital 4-Month

NegativeRemodeling /Recoil

15 Months after AMS implantation in human

IVUS OCT

Courtesy of Pr. Carlo di Mario

• Very thin neointima

• perfect ingrow of AMS

• completed healing of the stented vessel

A B

C D

Bare Metal Stent

AbsorbableMetal Stent

AMS: AMS: 16-row MSCT 16-row MSCT CompatibleCompatible

Lind et al Heart 91:1604, 2005

Stent Resorption and Vasoreactivity?

2.7

2.75

2.8

2.85

2.9

2.95

3

3.05

3.1

3.15

Pre ISDN Post ISDN

Dia

met

er (

mm

)

Pre-ISDN

Post-ISDN

Stent segment

passivatingmatrix

Mid / long term

Addition of suitable drug

Passivating coating

Short term: AMS2

The future of the AMS platformThe future of the AMS platform

Reduction ofDegradation Rate

Increase ofRadial Force

Optimization of mechanical stability

Improved Geometrical Design

ImprovedAlloy / Metallography

Inhibition ofside effects

DREAMS

Use AMS2as basic platform