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

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

7. Performance should mimic that of a metallic DES
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 Cohort B XIENCE V
(mmHg)
Radial Strength MSI Testing
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
Leukocyte Recruitment
Re-endothelialization
Everolimus Elution
Platelet Deposition
Matrix Deposition
Support
SMC Proliferation and Migration
Vascular Function
Full Mass Loss & Bioabsorption
Mass Loss 1 3 6
Mos
2 Yrs
Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.

11. Transition from vessel scaffolding to discontinuous structure
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
PLA – Poly Lactic Acid
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%
A subset of patients were studied using Optical Coherence Tomography (OCT) at 6 months. OCT provides very high resolution imaging, which is ideal for observing the interaction between the stent struts and the vessel over time.
At baseline, 91% of the stent struts were fully apposed in these patients. Most of the non-apposed struts were struts spanning across side branches. At 6-month follow-up, stent strut apposition remained very good, with 92% of struts apposed. Nearly all struts (99%) were covered with tissue at 6 months, which is an encouraging finding.
One of the more interesting findings was the change in optical appearance of the struts over time, which could be an early indication of bioabsorption.
N = 13 devices, 671 struts
Complete
Incomplete
Ormiston, J, et al. Lancet 2008; 371:

14. Mechanical Conditioning
Leukocyte Recruitment - Inflammation
Matrix Deposition - Remodeling
Re-endothelialization
Everolimus Elution
Support
Platelet Deposition - Thrombosis
SMC Proliferation and Migration
Vascular Function
Full Mass Loss & Bioabsorption
Mass Loss 1 3 6
Mos
2 Yrs
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
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, …
Ciccone, W. et al. J Am Acad Orthop Surg. 2001;9:

17. Phases of Functionality
Revascularization
Restoration
Resorption
Leukocyte Recruitment
Re-endothelialization
Everolimus Elution
Platelet Deposition
Matrix Deposition
Support
SMC Proliferation and Migration
Vascular Function
Full Mass Loss & Bioabsorption
Mass Loss 1 3 6
Mos
2 Yrs
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
Here are some representative histology slides from one of our safety studies in a porcine model. In this study, the BVS stent and a Cypher stent were implanted in each animal – we used the Cypher as a control since it is an approved DES.
The neointimal response was comparable between the two implants at 28 and 90 days in terms of neointimal composition and coverage. At later time points, however, the neointimal response to BVS stents was milder.
Photos taken by and on file at Abbott Vascular.
Tests performed by and data on file at Abbott Vascular.
NOTE TO PRESENTERS: you may get a comment about the non-uniform strut distribution in the BVS 1 month image. This slice likely cut through part of a ring (from 11 o’clock to 5 o’clock) and one of the links (at 9 o’clock). Our next generation device has a new cell pattern that provides more uniform coverage. You might also hear a comment that it appears the struts are still there at 1 year. The material is fully absorbed in months, so it is not surprising to still see struts at 1 year. We know from additional porcine model testing that vasomotion in the BVS stented segment is restored by this 12-month timepoint (shown by intracoronary injection of acetylcholine causing vasoconstriction)

19. BVS: Minimal Inflammation
Porcine Coronary Artery Model
Inflammation Score (0-4) 1 2 3 4
3 Mo
6 Mo
12 Mo
18 Mo
24 Mo
36 Mo
BVS associated Inflammation markedly less than Cypher
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. Vessel is returned to a more natural state
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. 21

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 Baudelaire