Bioabsorbable Stents The Ideal Scaffold properties and kinetics Jonathan Hill King’s College...
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Transcript of Bioabsorbable Stents The Ideal Scaffold properties and kinetics Jonathan Hill King’s College...
Bioabsorbable Stents
The Ideal Scaffoldproperties 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
• 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 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
Avera
ge M
id W
all C
urv
atu
re (
mm
)
LESSConformable
MOREConformable
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 AcidLactic Acid
PLAPLA
Molecular Weight Molecular Weight
H2O
Hydrolysis
Mass LossMass Loss
Krebs
Cycle
Krebs
Cycle
Mass TransportMass Transport
CO2 + H2O
RO
R′OH2O+ R
OR′
OHHO+
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 IncompleteOrmiston, 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
SupportVascular Function
Gradual disappearance of supportive structure
Vessel recovers the ability to respond to physiologic stimuli
Shear stress & pulsatility
Tissue adaptation
Structure and functionality
Mechanical ConditioningBioabsorbable 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
“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