Bioabsorbable Stents. The Ideal Scaffold properties and kinetics. Jonathan Hill King s College Hospital King s Health Partners

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1 Bioabsorbable Stents The Ideal Scaffold properties and kinetics Jonathan Hill King s College Hospital King s Health Partners

2 Transient Biodegradable Scaffold Building a skyscraper in Hong Kong with bamboo scaffold

3 Transient Scaffolding

4 The Ideal Bioresorbable Scaffold Properties and Kinetics The 3 Rs 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.

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

6 Phases of Functionality Revascularization Restoration Resorption Drug Elution Support Mass Loss Full Mass Loss & Bioabsorption Mos 2 Yrs Platelet Deposition Leukocyte Recruitment SMC Proliferation and Migration Matrix Deposition Re-endothelialization Vascular Function 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 (mmhg) Radial Strength MSI Testing Cohort B XIENCE V Tests performed by and data on file at Abbott Vascular. Radial strength comparable to metal stent at T=0

9 Average Mid Wall Curvature (mm Addressing Vessel/Implant Compliance Mismatch Original PVA vessel curvature LESS Conformable 5 0 MULTI-LINK VISION (permanent metallic stent) BVS (temporary implant) MORE Conformable Tests performed by and data on file at Abbott Vascular.

10 Phases of Functionality Revascularization Restoration Resorption Everolimus Elution Support Mass Loss Full Mass Loss & Bioabsorption Mos 2 Yrs Platelet Deposition Leukocyte Recruitment SMC Proliferation and Migration Matrix Deposition Re-endothelialization Vascular Function 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 Molecular Weight H 2 O Hydrolysis PLA Poly Lactic Acid Lactic Acid Mass Loss Mass Transport R O O R O + H 2 O R + OH carboxylic acid HO R alcohol Kreb s Cycle CO 2 + H 2 O

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

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

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

16 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: J Am Acad Orthop Surg, Vol 9, No 5, September/October 2001, 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,

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

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

19 BVS: Minimal Inflammation Porcine Coronary Artery Model Inflammation Score (0-4) 4 3 BVS associated Inflammation markedly less than Cypher Mo 6 Mo 12 Mo 18 Mo 24 Mo 36 Mo Benign bioabsorption with minimal inflammation observed beyond 1 year BVS Cypher 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 The Ideal Scaffold- Properties and Kinetics REVASCULARISATION As effective as a DES RESORPTION Transient RESTORATION Restores natural vascular response

23 Acknowledgements Richard Rapoza Tony Gershlick Jonathan Hill

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