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Bioabsorbable Stents
The Ideal Scaffoldproperties and kinetics
Jonathan Hill
• King’s College Hospital
• King’s Health Partners
TransientBiodegradable 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 restorationtherapy”
– 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
883991
(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
Av
era
ge
Mid
Wa
ll C
urv
atu
re (
mm
)
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
RO
R′O
H2O+ RO
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 = backgroundTests 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 1857Baudelaire 1821- 1867
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