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Transcript of Bioabsorbable Stents 2016-12-16¢  Mechanical Conditioning Bioabsorbable orthopedic...

  • Bioabsorbable Stents

    The Ideal Scaffold properties 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

    883 991

    (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

    A v

    e ra

    g e

    M id

    W a

    ll C

    u rv

    a tu

    re (

    m m

    )

    LESS

    Conformable

    MORE

    Conformable

    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 Acid

    PLA

     Molecular Weight

    H2O

    Hydrolysis

    Mass Loss

    Kreb

    s

    Cycle

    Mass Transport

    CO2 + H2O

    R O

    R′O

    H2O+ R O

    R′

    OH

    HO+

    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 Incomplete

    Ormiston, 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

    Support

    Vascular

    Function

    Gradual disappearance of

    supportive structure

    Vessel recovers the ability to

    respond to physiologic stimuli

    Shear stress & pulsatility

    Tissue adaptation

    Structure and functionality

  • Mechanical Conditioning

    Bioabsorbable 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 = background Tests 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