Bioabsorbable Stents

The Ideal Scaffoldproperties and kinetics

Jonathan Hill• King’s College Hospital• King’s Health Partners

Transient Biodegradable Scaffold

• Building a skyscraper in Hong Kong with bamboo scaffold

Transient Scaffolding

• REVASCULARISATION- As effective as a DES

– Platform and Drug

• RESTORATION- Restores natural vascular response—”Vascular restoration therapy”

– Improved reendothelialisation and no long term inflammation,

– Further intervention and non invasive imaging possible

• RESORPTION- Transient

– No permanent metallic implant.

The Ideal Bioresorbable Scaffold – Properties and Kinetics The 3 Rs

Properties and Kinetics for a Bioabsorbable Device

1 3 6 2 Yrs

Full Mass Loss & Bioabsorption

Mos

Platelet Deposition

Leukocyte Recruitment

SMC Proliferation and Migration

Matrix Deposition

Re-endothelialization

Vascular Function

Drug Elution

Support

Mass Loss

Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

Phases of Functionality

1 3 6 2 Yrs

Full Mass Loss & Bioabsorption

Mos

Platelet Deposition

Leukocyte Recruitment

SMC Proliferation and Migration

Matrix Deposition

Re-endothelialization

Vascular Function

Drug Elution

Support

Mass Loss

Revascularization Restoration Resorption

Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

Revascularization Phase (0 – 3 months)

Design Requirements: • Good deliverability

• Minimum of acute recoil

• High acute radial strength

• Therapeutic agent delivered to abluminal tissue at a controlled rate

• Excellent conformability

Performance should mimic that of a metallic DES

Radial Strength

Radial strength comparable to metal stent at T=0

0

200

400

600

800

1000

1200

1400

1600

1800

Radial Strength MSI Testing

XIENCE VCohort B

883991

(mmHg)

Tests performed by and data on file at Abbott Vascular.

Addressing Vessel/Implant Compliance Mismatch

0

5

10

15

20

25

30

35

MULTI-LINK VISION BVS

Avera

ge M

id W

all C

urv

atu

re (

mm

)

LESSConformable

MOREConformable

Original PVA vessel curvature

(permanent metallic stent) (temporary implant)

Tests performed by and data on file at Abbott Vascular.

Phases of Functionality

1 3 6 2 Yrs

Full Mass Loss & Bioabsorption

Mos

Platelet Deposition

Leukocyte Recruitment

SMC Proliferation and Migration

Matrix Deposition

Re-endothelialization

Vascular Function

Everolimus Elution

Support

Mass Loss

Revascularization Restoration Resorption

Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

Design Requirements: • Gradually lose radial strength

• Struts must be incorporated into the vessel wall (strut coverage)

• Become structurally discontinuous

• Allow the vessel to respond naturally to physiological stimuli

Transition from vessel scaffolding to discontinuous structure

Restoration Phase (3 months Structural Discontinuity)

Poly Lactide - Hydrolysis

PLA – Poly Lactic Acid

Lactic AcidLactic Acid

PLAPLA

Molecular Weight Molecular Weight

H2O

Hydrolysis

Mass LossMass Loss

Krebs

Cycle

Krebs

Cycle

Mass TransportMass Transport

CO2 + H2O

RO

R′OH2O+ R

OR′

OHHO+

carboxylic acid alcohol

Strut Coverage: ABSORB 6-Month OCT Results

Complete Incomplete

Strut Coverage – 6 Mos. F/U

N = 13 devices, 671 struts

99%

1%

Complete IncompleteOrmiston, J, et al. Lancet 2008; 371: 899-907.

Mechanical Conditioning

1 3 6 2 Yrs

Full Mass Loss & Bioabsorption

Mos

Platelet Deposition - Thrombosis

Leukocyte Recruitment - Inflammation

SMC Proliferation and Migration

Matrix Deposition - Remodeling

Re-endothelialization

Vascular Function

Everolimus Elution

Support

Mass Loss

Vascular Function

Mechanical Conditioning

SupportVascular Function

Gradual disappearance of supportive structure

Vessel recovers the ability to respond to physiologic stimuli

Shear stress & pulsatility

Tissue adaptation

Structure and functionality

Mechanical ConditioningBioabsorbable orthopedic implants offer the advantage of gradual load transfer (mechanical conditioning) and improved healing versus stress shielding concerns seen with metallic implants

Ciccone, W. et al. J Am Acad Orthop Surg. 2001;9:280-288.

J Am Acad Orthop Surg, Vol 9, No 5, September/October 2001, 280-288.

Bioabsorbable Implants in Orthopaedics: New Developments and

Clinical Applications

William J. Ciccone, II, MD, Cary Motz, MD, Christian Bentley, MD and James P. Tasto, MD

The use of bioabsorbable implants in orthopaedic surgical procedures is becoming more frequent. Advances in polymer science have allowed the production of implants with the mechanical strength necessary for such procedures. Bioabsorbable materials have been utilized for the fixation of fractures as well as for soft-tissue fixation. These implants offer the advantages of gradual load transfer to the healing tissue, reduced need for hardware removal, and radiolucency, which facilitates postoperative radiographic evaluation. Reported complications with the use of these materials include sterile sinus tract formation, osteolysis, synovitis, and hypertrophic fibrous encapsulation. Further study is required to determine the clinical situations in which these materials are of most benefit.

Bioabsorbable…implants offer the advantages of gradual load transfer to the healing tissue, …

Phases of Functionality

1 3 6 2 Yrs

Full Mass Loss & Bioabsorption

Mos

Platelet Deposition

Leukocyte Recruitment

SMC Proliferation and Migration

Matrix Deposition

Re-endothelialization

Vascular Function

Everolimus Elution

Support

Mass Loss

Revascularization Restoration Resorption

Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

Porcine Coronary Safety Study:Representative Photomicrographs (2x)

BVS

CYPHER

Photos taken by and on file at Abbott Vascular.

2 years1 month 6 months 1 year 3 years

1 month 6 months 1 year 2 years 3 years

4 years

4 years

Tests performed by and data on file at Abbott Vascular.

BVS: Minimal Inflammation

Inflammation Score (0-4)

BVS associated Inflammation markedly less than Cypher

Benign bioabsorption with minimal inflammation observed beyond 1 year

Porcine Coronary Artery Model

Inflammation score ≤ 1 = backgroundTests performed by and data on file at Abbott Vascular.

0

1

2

3

4

3 Mo 6 Mo 12 Mo 18 Mo 24 Mo 36 Mo

BVS Cypher

Resorption Phase (Structural Discontinuity Resorption)

Potential benefits: • Cellular/extracellular organization (vascular integrity)

• Return of vascular function

• Address current DES concerns

• Late lumen enlargement

• Durability of clinical outcomes

Vessel is returned to a more natural state

1 month 36 month

a-actin stain

At 36 months, SMCs are well organized and phenotypically contractile

Resorption Phase (Structural Discontinuity Resorption)

Restoration of vascular integrity in porcine model

Tests were performed by and data are on file at Abbott Vascular.

• REVASCULARISATION

– As effective as a DES

• RESORPTION

–Transient

• RESTORATION

–Restores natural vascular response

The Ideal Scaffold- Properties and Kinetics

Acknowledgements

• Richard Rapoza• Tony Gershlick

• Jonathan Hill jmhill@nhs.net

“Modernity is the transient, the fleeting;

it is the one half of art, the other, the other being the eternal and the immovable”

Les Fleurs du Mal 1857 Baudelaire 1821- 1867