Transcript Support Vascular Function

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
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.
Properties and Kinetics for a Bioabsorbable Device
Support
Full Mass Loss &
Bioabsorption
Drug Elution
1
Mass Loss
3
6
Mos
Platelet Deposition
Matrix Deposition
Leukocyte Recruitment
Re-endothelialization
SMC Proliferation and Migration
Vascular Function
Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.
2 Yrs
Phases of Functionality
Revascularization
Restoration
Resorption
Support
Full Mass Loss &
Bioabsorption
Drug Elution
Mass Loss
1
3
6
Mos
Platelet Deposition
Matrix Deposition
Leukocyte Recruitment
Re-endothelialization
SMC Proliferation and Migration
Vascular Function
Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.
2 Yrs
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
Radial Strength
Radial Strength MSI Testing
(mmHg)
1800
1600
1400
1200
1000
991
883
800
600
400
200
0
Cohort B
XIENCE V
Radial strength comparable to metal stent at T=0
Tests performed by and data on file at Abbott Vascular.
Average Mid Wall Curvature (mm)
Addressing Vessel/Implant Compliance Mismatch
35
LESS
Conformable
30
Original
PVA vessel
curvature
25
20
15
10
MORE
Conformable
5
0
MULTI-LINK VISION
(permanent metallic stent)
Tests performed by and data on file at Abbott Vascular.
BVS
(temporary implant)
Phases of Functionality
Revascularization
Restoration
Resorption
Support
Full Mass Loss &
Bioabsorption
Everolimus Elution
1
3
Mass Loss
6
Mos
Platelet Deposition
Matrix Deposition
Leukocyte Recruitment
Re-endothelialization
SMC Proliferation and Migration
Vascular Function
Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.
2 Yrs
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
Poly Lactide - Hydrolysis
PLA – Poly Lactic Acid
PLA
H2O
 Molecular Weight
Hydrolysis
Lactic Acid
O
Mass Loss
O
R
+
O
R′
Mass Transport
Kreb
s
Cycle
CO2 + H2O
H2O
R
+
OH
carboxylic acid
HO
R′
alcohol
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: 899-907.
Incomplete
Mechanical Conditioning
Vascular Function
Support
Full Mass Loss &
Bioabsorption
Everolimus Elution
1
3
Mass Loss
6
Mos
Platelet Deposition - Thrombosis
Matrix Deposition - Remodeling
Leukocyte Recruitment - Inflammation
Re-endothelialization
SMC Proliferation and Migration
Vascular Function
2 Yrs
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
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, 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
Bioabsorbable…implants
offer thethe
advantages
clinical situations in which these materials are of most benefit.
load transfer to the healing tissue, …
Ciccone, W. et al. J Am Acad Orthop Surg. 2001;9:280-288.
of gradual
Phases of Functionality
Revascularization
Restoration
Resorption
Support
Full Mass Loss &
Bioabsorption
Everolimus Elution
1
3
Mass Loss
6
Mos
Platelet Deposition
Matrix Deposition
Leukocyte Recruitment
Re-endothelialization
SMC Proliferation and Migration
Vascular Function
Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.
2 Yrs
Porcine Coronary Safety Study:
Representative Photomicrographs (2x)
BVS
1 month
6 months
1 year
2 years
3 years
4 years
6 months
1 year
2 years
3 years
4 years
CYPHER
1 month
Photos taken by and on file at Abbott Vascular.
Tests performed by and data on file at Abbott Vascular.
BVS: Minimal Inflammation
Porcine Coronary Artery Model
Inflammation Score (0-4)
4
BVS associated Inflammation
markedly less than Cypher
3
2
Benign bioabsorption with
minimal inflammation observed
beyond 1 year
1
0
3 Mo
6 Mo
BVS
12 Mo
18 Mo 24 Mo
36 Mo
Cypher
Inflammation score ≤ 1 = background
Tests performed by and data on file at Abbott Vascular.
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
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.
The Ideal Scaffold- Properties and Kinetics
• REVASCULARISATION
– As effective as a DES
• RESORPTION
–Transient
• RESTORATION
–Restores natural vascular response
Acknowledgements
• Richard Rapoza
• Tony Gershlick
• Jonathan Hill [email protected]
“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