Bioabsorbable Stents

1. Bioabsorbable Stents The Ideal Scaffold properties and kinetics Jonathan Hill • King’s College Hospital • King’s Health Partners BIOABSORBABLE STENTS Chairs: Carlo di Mario and Julian Gunn 11:25 The ideal scaffold – properties and kinetics Jonathan Hill 11:35 The current players Adrian Banning 11:45 Early clinical results Angela Hoye 12:05 Regulatory issues Susanne Ludgate 12:10 Panel Discussion

2. TransientBiodegradable Scaffold • Building a skyscraper in Hong Kong with bamboo scaffold

3. Transient Scaffolding

4. 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 BioresorbableScaffold – Properties and Kinetics The 3 Rs

5. Properties and Kinetics for a Bioabsorbable Device Support Full Mass Loss & Bioabsorption Drug Elution Mass Loss Platelet Deposition Matrix Deposition Leukocyte Recruitment Re-endothelialization SMC Proliferation and Migration Vascular Function 3 1 2 Yrs 6 Mos Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

6. Phases of Functionality Revascularization Restoration Resorption Support Full Mass Loss & Bioabsorption Drug Elution Mass Loss Platelet Deposition Matrix Deposition Leukocyte Recruitment Re-endothelialization SMC Proliferation and Migration Vascular Function 3 1 2 Yrs 6 Mos Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

7. Revascularization Phase (0 – 3 months) Performance should mimic that of a metallic DES Design Requirements: • Good deliverability • Minimum of acute recoil • High acute radial strength • Therapeutic agent delivered to abluminal tissue at a controlled rate • Excellent conformability

8. Radial Strength Radial Strength MSI Testing (mmHg) 991 883 Cohort B XIENCE V Radial strength comparable to metal stent at T=0 Tests performed by and data on file at Abbott Vascular.

9. Addressing Vessel/Implant Compliance Mismatch LESS Conformable Original PVA vessel curvature MORE Conformable (permanent metallic stent) (temporary implant) Tests performed by and data on file at Abbott Vascular.

10. Phases of Functionality Revascularization Restoration Resorption Support Full Mass Loss & Bioabsorption Everolimus Elution Mass Loss Platelet Deposition Matrix Deposition Leukocyte Recruitment Re-endothelialization SMC Proliferation and Migration Vascular Function 3 1 2 Yrs 6 Mos Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

11. Restoration Phase (3 months  Structural Discontinuity) Transition from vessel scaffolding to discontinuous structure 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

12. Poly Lactide - Hydrolysis PLA – Poly Lactic Acid PLA H2O  Molecular Weight Hydrolysis Lactic Acid O O Mass Loss R + H2O R + HO R′ O R′ OH carboxylic acid alcohol Mass Transport CO2 + H2O Krebs Cycle

13. Strut Coverage: ABSORB 6-Month OCT Results Strut Coverage – 6 Mos. F/U 1% 99% N = 13 devices, 671 struts Complete Incomplete Ormiston, J, et al. Lancet 2008; 371: 899-907.

14. Mechanical Conditioning Support Full Mass Loss & Bioabsorption Everolimus Elution Mass Loss Platelet Deposition - Thrombosis Matrix Deposition - Remodeling Leukocyte Recruitment - Inflammation Re-endothelialization SMC Proliferation and Migration Vascular Function Vascular Function 3 1 2 Yrs 6 Mos

15. Mechanical Conditioning Vascular Function Support Gradual disappearance of supportive structure Vessel recovers the ability to respond to physiologic stimuli Shear stress & pulsatility Tissue adaptation Structure and functionality

16. Mechanical Conditioning 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, … 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.

17. Phases of Functionality Revascularization Restoration Resorption Support Full Mass Loss & Bioabsorption Everolimus Elution Mass Loss Platelet Deposition Matrix Deposition Leukocyte Recruitment Re-endothelialization SMC Proliferation and Migration Vascular Function 3 1 2 Yrs 6 Mos Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

18. Porcine Coronary Safety Study:Representative Photomicrographs (2x) BVS 1 month 1 year 4 years 3 years 2 years 6 months CYPHER 1 month 6 months 3 years 4 years 1 year 2 years Tests performed by and data on file at Abbott Vascular. Photos taken by and on file at Abbott Vascular.

19. BVS: Minimal Inflammation 4 3 2 1 0 3 Mo 6 Mo 12 Mo 18 Mo 24 Mo 36 Mo Porcine Coronary Artery Model Inflammation Score (0-4) BVS associated Inflammation markedly less than Cypher Benign bioabsorption with minimal inflammation observed beyond 1 year Cypher BVS Inflammation score ≤ 1 = background Tests performed by and data on file at Abbott Vascular.

20. Resorption Phase (Structural Discontinuity  Resorption) Vessel is returned to a more natural state Potential benefits: • Cellular/extracellular organization (vascular integrity) • Return of vascular function • Address current DES concerns • Late lumen enlargement • Durability of clinical outcomes

21. Resorption Phase (Structural Discontinuity  Resorption) Restoration of vascular integrity in porcine model 1 month 36 month a-actin stain At 36 months, SMCs are well organized and phenotypically contractile Tests were performed by and data are on file at Abbott Vascular.

22. REVASCULARISATION As effective as a DES RESORPTION Transient RESTORATION Restores natural vascular response The Ideal Scaffold- Properties and Kinetics

23. Acknowledgements • Richard Rapoza • Tony Gershlick • Jonathan Hill jmhill@nhs.net

24. “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