biomaterials in medical devices - tor vergataissues of biomaterials in medical devices. 15/40 •...
TRANSCRIPT
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Biomaterials in Medical Devices
Eunsung Park, Ph.D.Medtronic Strategy and Innovation
Medtronic, [email protected]
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Contents of Lectures• Overview of Biomaterials
– Biomaterials and Biocompatibility• Overview of Medical Devices
– Focus on implantable, therapeutic devices• Heart Valves
– Mechanical valves and Bioprosthesis• Stents
– Stent delivery system– Bare metal stents and Drug eluting stents
• Pacemakers and ICDs– Components– MRI compatibility issues
• Surface Properties– Surface energy– Surface treatments and coatings
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Introduction
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Materials Science and Engineering
Transparent Plane??!@!
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What are biomaterials?
• Materials used to make devices to replace a part of a function of the body in a safe, reliable, economic, and physiologically acceptable manner. (Hench and Erthridge, 1982)
• A nonviable material used in a medical device intended to interact with biological systems. (Williams 1987)
Biomaterials are used in medical devices in direct contact with biological systems.Biomaterials are defined by their application, NOT chemical make-up.
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Study of Biomaterials S&E
• Interdisciplinary, integrated, sophisticated– materials science + biology + physiology +
biochemistry + clinical science + …
• Wide range of materials– metals, ceramics, polymers, composites,
biological materials
– in a biological environment
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MIT OCW
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– Stainless Steel– Ti and alloys– Co alloys– NiTi– Pt-Ir, Ta– Au
Metallic Biomaterials
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• Advantages– Properties and fabrication well
known– High mechanical strength– Stiff and strong– Fatigue resistance, wear
resistance– Joining technologies known
• Disadvantages– Corrosion– Metal ions may be toxic
Metallic Biomaterials
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– Pyrolytic carbon, Diamond-like carbon– Alumina, Zirconia– Hydroxyapatite / Calcium phosphates– Bioglasses– A/W glass-ceramic
BioCeramics
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• Advantages• Similar in physical properties to bone• Readily sterilized• High compressive strength when dense• Low to high bioreactivity
• Disadvantages• Difficult to fabricate• Low strength in tension, torsion, bending,
or impact
BioCeramics
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– Silicone– Polyurethane; Polyethylene: PE– Poly(methyl methacrylate): PMMA– Poly(ethylene terephthalate): PET (Dacron®)– Poly(tetrafluoroethylene): PTFE (Teflon®)– Hydrogels– Bioresorbable (biodegradable) polymers
• PGA, PLA, PGLA, Polycaprolactone
Polymer Biomaterials
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• Advantages– Easy fabrication– Wide range of compositions and properties– Many ways to immobilize biomolecules/
cells
• Disadvantages– Contain leachable compounds
• Additives (stabilizers, plasticizers, etc.)
– Surface contamination– Chemical/ biochemical degradation
• Mobility
– Difficult to sterilize
Polymer Biomaterials
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Applications of Biomaterials
• Orthopedic– artificial hips, knees, shoulders, wrists; intervertebral discs; fracture
fixation; bone grafts
• Cardiovascular– heart valves, pacemakers, catheters, grafts, stents, PTCA balloons
• Dental– enamels, fillings, prosthetics, orthodontics
• Soft tissue– wound healing, reconstructive and augmentation, intra-ocular lens
• Surgical– staples, sutures, scalpels, surgical tools
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Criteria for Biomaterials as Implants
• Have required physical/chemical properties and maintain these properties over desired time period.
• Do not induce undesirable biologic responses.
• Should be manufactured and sterilized easily and reproducibly.
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• Physical Properties– Mechanical properties, tensile, compressive, fatigue– Transport properties– Degradation rate, degradation products– Surface properties, chemistry, morphology, roughness
• Biological interactions– Materials-Body interactions– Toxicity, Decomposition
• Formability• Design Issues• Liability
Issues of Biomaterials in Medical Devices
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• Understanding and controlling performance– Physical, Chemical, Biological
• Relevant material performance under biological conditions– 37 C, aqueous, saline, extracellular matrix (ECM)
– Material properties as a function of time• Initial negative biological response - toxicity
• Long term biological response – rejection
• Biology is a science of surfaces and interfaces and it is never at equilibrium.
Cont’d
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Value LocationpH 6.8 Intracellular 7.0 Interstitial 7.15-7.35 BloodpO2 2-40 Interstitial (mm Hg) 40 Venous 100 ArterialTemperature 37 Normal Core 28 Normal SkinMechanical Stress 4x107 N m-2 Muscle (peak stress) 4x108 N m-2 Tendon (peak stress)Stress Cycles (per year) 3x105 Peristalsis 5x106 - 4x107 Heart muscle contraction
Length of implant: Day, Month, Years
Test Conditions:
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Biocompatibility
– Old Definition• Non-irritant, Non-toxic, Non-carcinogenic, Non-
allergenic, etc.
– New Definition• The ability of a material to perform with an
appropriate host response in a specific application.» D. Williams
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Biocompatibility
• Is a collection of processes involving interactions between the materials and the tissue.
• Refers to the ability of the material to perform a function.
• Refers to the appropriate host responses.– Does not stipulate that there should be no responses.
• Is NOT an intrinsic material property.
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Assessing Biocompatibility
• Question: Will this material stimulate the appropriate biological response for the intended use?
• In vitro tests• In vivo/Usage tests
• Clinical Trials
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In Vitro Analysis of Cell/Biomaterial Interactions
• Nature of cell/biomaterial interactions
• Fundamental phenotypic/functional differences
• Soft/hard tissue cells
• Cell number, growth rate, metabolic rate, cell function, protein expression
• Simple, repeatable, inexpensive, rapid
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In Vivo Tests
• Relevant mammalian model
• Comprehensive biological response
• Ethical concerns
• Expensive & time-consuming
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Clinical Trials
• Most relevant test
• Safety and efficacy test
• All other tests measured against this
• Expensive, logistically complicated
• Difficult to interpret results
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Biological Responses to Biomaterials
– In Tissue• Inflammation, Fibrous Tissue Formation, Immune
Response, Infection, Necrosis
– In Blood• Thrombosis, Lipid or Mineral Deposition, Infection
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Types of Implant-Tissue Response
If the material is Response
toxic the surrounding tissue dies
nontoxic and nearly inert a fibrous tissue forms
nontoxic and bioactive an interfacial bond forms
nontoxic and dissolves the surrounding tissue replaces it
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Why do Medical Devices Fail?
• The types of materials failure in the failure of biomedical devices– Mechanical– Physico-chemical– Chemical (biochemical, electrochemical)– Device Design
• Device failure can be catastrophic to the patient and, at the least, costly and risky– We often don’t have good long term descriptive tests for
medical devices in-vivo– High risk nature precludes new device adoption
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Mechanisms of Biomaterial Breakdown
Mechanism Breakdown
Mechanical Creep, Wear, Stress cracking, Fracture
Physico-chemical Adsorption of biomolecules (fouling),
Absorption of water (softening), Desorption of low MWs (weakening), Dissolution
Biochemical Hydrolysis, Oxidation, Reduction, Mineral deposition
Electrochemical Corrosion
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Mechanical Failure
• Mechanisms:– Creep: Long term deformation under load– Wear/Abrasion: Surface failure during working– Stress cracking: Stress relief in local environment– Fatigue: Breaking under cycling load– Tensile/Torsion/Compression failure
• Issues:– Material choice– Testing– Failure analysis: fractography
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Fractography: ductile fracture
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Fractography: brittle fracture
•Mirror
•Mist
•Hackle
http://www.doitpoms.ac.uk/tlplib/fracture/images/glass2.gif
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Physico-chemical / Chemical Failure
• Protein/cell adsorption on the surface - fouling• Property decay through water interactions –
softening, crazing• Leaching of plasticizer, filler, etc. in bio environment • Dissolution of component/device• Materials degradation of device - hydrolysis of
esters or amides• Corrosion - oxidation or reduction• Calcification - “growing unwanted bone” or Ca
deposits• Catastrophic fibrous encapsulation
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Material Selection Factors• Mechanical
tensile, compression, dynamic, fracture, stress, strain, stiffness, creep, fatigue
• Electricalresistance, contact, power supply, earthing, insulation, electromechanical
compatibility• Thermal
shrinkage, expansion, stability, insulation• Chemical
(bio)stability, degradation, corroision, interaction/reaction• Environmental
product life span, shelf life, humidity, manufacturing waste, recyclability• Surface
finish, wear, friction, tactility (“feel”)• Aesthetic
Cosmetic appearance, colors, visual clarity• Economic
Material cost, process introduction
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Medical Device Sterilization
• To kill the microorganisms
• Sterilization processes– E-beam
– Gamma radiation
– Ethylene oxide (EtO)
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Medical Device Sterilization
• E-beam– Accelerated high energy electrons (10MeV)
– Damages DNAs
– E-beam causes crosslinking and chain scissoring of polymers (Teflon, PP, etc.)
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Medical Device Sterilization
• Gamma radiation– Radioisotope (Co60) generated
gamma rays
– Damages DNAs and cellular structures
– Quick turnaround; easy penetration
– Not for some polymers: acetyls, Teflon, PP
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Medical Device Sterilization
• Ethylene oxide (EtO)– Ethylene oxide gas, temperature, humidity
– Disrupts DNAs
– For nearly all materials
– Takes long time: pre-condition (T, humidity), sterilization, aeration
– Aeration is particularly a problem for polymers (absorbed must be desorbed)
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Effects of Sterilization• Radiation process: e-beam and
gamma– Radiation affects materials with
low binding energy.• Energy of radiation breaks the
molecular bonds.
– For some polymers (acetyls, Teflon, PP), crosslinking or scissoring occurs.
– It also affects batteries and electronic components.
– Gamma radiation changes the color grade of ceramics.
• ZrO2 hip balls turn dark after sterilization.
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Effects of Sterilization
• Ethylene oxide (EtO)– Aeration is particularly a problem for polymers and porous
materials.
– Polymers absorb EtO easily. Sterilization is effective, however, all absorbed EtO must be removed (aeration).
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Bio-Materials Technologypast, present, future…
BIOmaterials
time
bioMATERIALS
BIOMATERIALS
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Evolution of Biomaterials
Structural
Functional Tissue Engineering Constructs
Soft Tissue Replacements
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Progression of Biomaterials Technologies: Compatibility
1960’s
Biostability
•Durability•Tolerance by body
1980’s
Biocompatibility
•Blood and tissue compatibility
Bio-Interactivity
“Living” implants• Modification of cells
2000
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Medical Devices
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What Is a Medical Device?
What is not?
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Definition of a Medical Device(by US FDA)
• “An instrument, apparatus, or implant intended for diagnosis, treatment, or prevention of disease ……affect the structure or function of the body without chemical action or metabolism”
• Range from simple tongue depressors to complex programmable pacemakers with micro-chip technology and laser surgical devices
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Classification of Medical Devices(by US FDA)
• Classification depends on three factors– Intended use - What disease, symptom, or
condition is the device intended to treat? How will the device be used?
– Indications for use - What kinds of patients should this be used on? Can be based on age, disease state, medical history, allergies, etc.
– Level of risk - Is the device life-saving? Is the device life-sustaining? Is there an unreasonable risk of illness or injury associated with use of the device?
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Classification of Medical Devices(by US FDA)
• Class I: General Controls– Present minimal potential for harm to the user
– Devices whose safety & effectiveness are well-established
– Registration with the FDA, GMP, proper labeling, notification of FDA before marketing
– About 40% of all devices are Class I
– Tongue depressor, bandages, exam gloves
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Classification of Medical Devices(by US FDA)
• Class II: General controls with specific controls– Subject to special controls of special labeling,
mandatory performance standards, postmarket surveillance, preclinical testing
– About half of all devices are Class II
– Contact lenses, x-ray machines, powered wheelchairs, infusion pumps, surgical needles, suture materials, acupuncture needles
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Classification of Medical Devices(by US FDA)
• Class III: General controls and Premarket Approval– Premarket approval, scientific reviews to ensure
the device’s safety and effectiveness
– Life-supporting or life-sustaining devices
– Less than 10% of all devices are Class III
– Heart valves, pacemakers, breast implants, stents
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Getting a Device to Market
• For a “Me Too” device– 510(k) Notification
– Manufacturer must show substantial equivalence to already marketed device.
• For a new device– Pre-market Approval (PMA)
– Manufacturer must show safety and effectiveness of new device.
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Substantial Equivalence
• A device is found substantially equivalent (SE) if, in comparison to a legally marketed device, it:– Has the same intended use, and– Has the same technological characteristics as the
pre-existing (predicate) device; or– Does not raise new questions of safety and
effectiveness, or demonstrates equal safety and effectiveness
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Premarket Approval
• For a New Device (in Class III)
• Premarket Approval (PMA) requires– Valid Scientific Evidence showing safety and
effectiveness
– Laboratory and Animal Study
– Clinical Study
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Classes of Medical Devices
• Diagnostic Devices• Monitoring Devices• Therapeutic Devices
----------------------------• External Devices
• Implanted Devices----------------------------
• Devices for Acute Care (short-term use)• Devices for Chronic Care (long-term use)
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• Diagnostic Devices
– Determine the cause of disease or injury– Examples
• Imaging (X-ray, CT, MRI) • DNA-base diagnostics; POC devices• Cardiac marker-base diagnostics
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• Monitoring Devices
– Determine the progress of therapy and the state of the patient in response to therapy
– Examples• Blood pressure• ECG• Blood oxygen monitor
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• Therapeutic Devices
– Change structure and function of the biological system to alter the course of disease
– Examples• Pacemakers• Stents• Spinal fixation devices• …
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Classes of Medical Devices• Diagnostic Devices• Monitoring Devices• Therapeutic Devices
----------------------------• External Devices
• Implanted Devices----------------------------
• Devices for Acute Care (short-term use)• Devices for Chronic Care (long-term use)
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√
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Implantable Therapeutic Medical Devices for Chronic Diseases
Most Advanced Technologies=
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Cardiac Rhythm DisordersSudden cardiac arrest Implantable cardioverter defibrillators (ICDs)
Heart failure Cardiac resynchronization systems (CRT)
Arrhythmias Pacemakers
Unexplained syncope Implantable diagnostic recorders
Disease management Internet-based information technology system
For full safety information, visit medtronic.com
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Spinal Conditions
Spinal deformities Fusion systems
Herniated discs Minimal Access Spinal Technologies (MAST), artificial discs
Acute tibial fractures Bone morphogenetic proteins
For full safety information, visit medtronic.com
Fixation Systems
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Cardiovascular DiseasesVascular disease Catheters, angioplasty balloons, implantable
stents, open-heart surgery perfusion and stabilization systems
Aortic disease Implantable stent grafts
Heart valve disease Artificial valves
For full safety information, visit medtronic.com
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Neurological DisordersMovement disorders Implantable deep brain stimulation systems
Chronic pain Implantable neurostimulation systems, drug-infusion systems
Hydrocephalus Implantable shunts (cerebrospinal fluid)
For full safety information, visit medtronic.com
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Urological and Digestive Disorders
Acid reflux Diagnostic tools
Gastroparesis Implantable gastric stimulation systems
Overactive bladder/urinary retention Implantable sacral stimulation systems
Enlarged prostate Radio frequency ablation systems
For full safety information, visit medtronic.com
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Diabetes
Glucose monitoring Real-time continuous glucose monitoring systems
Insulin delivery External and implantable insulin pumps
Disease management Internet-based information technology system
For full safety information, visit medtronic.com
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Bio-Materials Technologypast, present, future…
BIOmaterials
time
bioMATERIALS
BIOMATERIALS
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Drugs
Biologics
Devices
Combin
ation
Combination
Com
bin a
ti on
Drugs
Biologics
Devices
Combination Products
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•Antibiotic bone cement and orthopedic implants
•Steroid eluting pacemaker
•Lumbar fusion device with growth factor
•Drug eluting stents
Combination Products
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Recently ApprovedCombination Products
• Transdermal patch for treatment of Parkinson’s disease
• Absorbable collagen sponge with genetically engineered human protein
• Transdermal patch for ADHD
• Transdermal patch for Depression
• Inhaled insulin for diabetes
• Dental bone grafting material with growth factor
• Surgical mesh with antibiotic coating
• Dermal iontophoresis system
• ……..Source: Office of Combination Products, FDA, www.fda.gov/oc/combination/approvals.html, as of May, 2007
http://www.fda.gov/oc/combination/approvals.html
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Miniaturization and longevity
Improved sensors and diagnostics
Enhanced biomaterials
Better disease prevention
Better technologies
Traditional Medical
Technology
Biotechnology
Nanotechnology
Information technology
+
Innovative Medical Technology
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Heart Valves
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Prosthetic Heart Valve
• A prosthetic (artificial) heart valve is a replacement for a diseased or dysfunctional heart valve.
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Heartand
HeartValves
Right Atrium
Right Ventricle
Left Ventricle
Left Atrium
Pulmonary Vein Aorta
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4 Heart Valves
Body
Lung
LungBody
Texas Heart Institute
•Tricuspid
•Mitral
•Pulmonary
•Aortic
Superior vena cava
Pulmonary artery
•Blood Flow: Body->RA->RV->Lung->LA->LV->Body
•Heart Pump: Atrial contraction (RA/LA->RV/LV)
Ventricular contraction (RV/LV->Lung/Body)
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Heart Valves
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Mitral Valve
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When is it used?
• Two conditions that may require a heart valve replacement are – Stenosis (smaller opening)
• Leaflets thicken or stiffen
– Regurgitation (incompetence)• Valve doesn’t close properly and blood leaks backward
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Type of Prosthetic Heart Valves
• Mechanical heart valves
• Biological heart valves
Medtronic Hancock II ® Medtronic Freestyle ® Medtronic Mosaic®
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Mechanical Heart Valves• Caged ball valve
– Occluder in restraining cage– 1960’s– Very durable, but suboptimal
hemodynamics
• Tilting disc valve– Single leaflet on a central strut– Good hemodynamics
• Bileaflet valve– Two leaflets rotate on pivots
St. Jude medical
Medtronic
Edwards
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Mechanical Heart Valves• Advantages
– The main advantage of mechanical valves is high durability. They usually last a lifetime.
• Disadvantages– Mechanical heart valves can increase the risk of blood
clots. Because of this, patients must take anticoagulant (blood thinners) for the rest of their lives.
– Even though blood thinners are relatively safe, they do increase the risk of bleeding in the body.
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Biological Heart Valves
• Stented– Mostly made from porcine aortic valves
or bovine pericardium– Preserved in glutaraldehyde (reduces
calcification)– Sewing ring provides structural stability– Some hemodynamic issues
• Stentless– Primarily made from aortic valves– Implanted on native valvular annulus w/o
a sewing cuff– Provides native anatomical and
hemodynamic profiles Medtronic Freestyle ®
Medtronic Mosaic®
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Biological Heart Valves• Advantages
– Excellent hemodynamics
– Less prone to thromboembolism. Anticoagulant therapy is generally not necessary.
• Disadvantages– Biological heart valves may wear out over time. They may
need to be replaced every 10 to 15 years.
– Calcification can be a problem. (More with young patients.)
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Materials in Mechanical Heart Valves
– Valve housing• CP Ti (grade 4), PyC coated cage,
Co-Cr alloys
– Sewing rings/cuffs• Polyester (Dacron), PTFE (Teflon)
– Occluder (Leaflet)• Pyrolytic carbon coated graphite
(W doped graphite)
•Most commonly used materials
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• CP Ti• All α-Ti (HCP)• ~99% Ti with O
• Grade 1 ~ 4 according to O content (0.18 ~ 0.4 %).
• Oxygen has a great influence on yield/fatigue strength and corrosion resistance, with acceptable ductility.
Properties Grade 1 Grade 2 Grade 3 Grade 4
Oxygen (w/o) 0.18 0.25 0.35 0.40
Tensile strength (MPa) 240 345 450 550
Yield strength (MPa) 170 275 380 485
Elongation (%) 24 20 18 15
Area reduction (%) 30 30 30 25
Oxygen Concentration and Mechanical Properties of CP Ti
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•Yield Strength to Density Ratio
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• Co-Cr Alloys• 2 major areas of use for the Co-Cr alloys are orthopedic
(prosthetic replacements, fixation devices) and cardiovascular (heart valve).
• Good corrosion resistance and mechanical properties• Co-Cr-Mo (F75, F799)
– Vitallium (Howmedica), Haynes-Stellite (Cabot), Zimaloy (Zimmer)
– Good corrosion resistance in chloride environment– Orthopedic, Dental
• Co-Ni-Cr-Mo (F562)– MP35N (SPS Technologies) – High strength/corrosion resistance– Good fatigue strength– Cardiovascular (stents)
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Relative Properties: Metals
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Pyrolytic Carbon• Similar to graphite, but with some covalent bonding
between its graphene sheets: disordered wrinkles and distortions within layers improved durability
• Belongs to turbostratic carbons• Produced by heating a hydrocarbon nearly to its
decomposition temperature, and permitting the graphite to crystallize (pyrolysis).
disordered
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• Is man-made.
• Is a coating.– Deposited through the thermal decomposition
of hydrocarbon (fluidized bed process)
– Coated on graphite• Pyrolysis takes place at high temperature
• Thermal expansion match
Pyrolytic Carbon
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• Inert and Biocompatible
• Thromboresistant (i.e. resistant to blood clotting) – not perfect (still needs anticoagulant)
• Good durability
• Good wear resistance
• Good strength
• High fracture toughness (~X20 higher than alumina)
Pyrolytic Carbon
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Allotropes of Carbon
Allotropes: structures with different molecular configurations
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PET and PTFE
• PET (polyethylene terephthalate)– High melting (Tm=260C) crystalline polymer– High tensile strength (~70 MPa)– Dacron® is a common commercial PET
• Available as woven fabric, knit graft
• PTFE (poly-tetrafluoroethylene)– PE with 4 H’s replaced with F’s– High melting (Tm=325C) polymer– Very hydrophobic and lubricious catheter, graft– Teflon®
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Medtronic Hancock II
Aortic/Mitral
– Valve • Porcine valves or Bovine pericardium• Entire porcine aortic root and aorta
(stentless)• Stiffened with glutaraldehyde (less
calcification, stable collagen cross-links)
– Sewing ring/skirt• Wire: Co-Ni alloy, Ni-Ti alloy• PET (Dacron), PTFE (Teflon)
Materials in Biological Heart Valves
•Most commonly used materials
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Percutaneous Valves• Still in early stage of development or infant clinical studies• Ability to be delivered to the heart using traditional cardiac
catheterization techniques (balloon catheter), through femoral artery (retrograde) or cardiac apex (anterograde).
• Heart does not need to be arrested during the operation –no need to use a bypass pump.
Edwards Transcatheter Valve
Cleveland Clinic
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Percutaneous Valves
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What Does it Take to Get a Surgical Valve to Market?
• Pre-Clinical In Vitro Testing (ISO 5840, FDA HV Guidance):– Hydrodynamic Performance Assessment
– Structural Testing/Analysis
– Material Assessment—biocompatibility, material property testing
• Pre-Clinical In Vivo Testing (ISO 5840, FDA HV Guidance):– Chronic animal study
• Clinical Study (ISO 5840, FDA HV Guidance):– Non-randomized study against objective performance criteria compiled
from currently marketed heart valves.
– Study not designed to show superiority, but rather safety/effectiveness against currently marketed valves.
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Pre-Clinical Hydrodynamic Test
• Hydrodynamic performance is compared with a clinically-approved reference valve– Steady, Pulsatile Flow Pressure Drop
• ΔP vs. Q – Steady, Pulsatile Flow Regurgitation and Leakage
– Flow Visualization to assess flow patterns through valve
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Pre-Clinical Structural Test
• Valve Durability Test (Accelerated Wear)– 200x106 cycles simulate five years implant
duration (tissue valves)– Performed at 10-15x physiologic heart rate– Periodic hydrodynamic testing and visual
examination is performed– Valve wear characteristics are compared to
clinically approved reference valve
• Valve Stent Structural Assessment – Finite Element Stress Analysis (FEA)– Fatigue analysis– Valve stent fatigue and creep testing
Leaflet Tearing--Pericardial valves
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Pre-Clinical In Vivo Testing
• Chronic animal study– 20-week implants, usually sheep
– “Control” animals implanted with clinically-approved reference heart valves for comparison
– Hemodynamic performance• Mean/peak pressure gradients,
effective orifice area, regurgitation, etc.
– Assess biological response to device
• Pathology, blood work, calcification, thrombus assessment
Biomaterials �in Medical DevicesContents of Lectures1_Biomaterials Overview.pdfIntroductionWhat are biomaterials?Study of Biomaterials S&EMetallic BiomaterialsBioCeramicsBioCeramicsPolymer BiomaterialsPolymer BiomaterialsApplications of BiomaterialsCriteria for �Biomaterials as ImplantsIssues of Biomaterials �in Medical DevicesCont’dBiocompatibilityAssessing BiocompatibilityIn Vitro Analysis of �Cell/Biomaterial InteractionsIn Vivo TestsClinical TrialsBiological Responses to BiomaterialsTypes of Implant-Tissue ResponseWhy do Medical Devices Fail?Mechanisms of Biomaterial BreakdownMechanical FailureFractography: ductile fractureFractography: brittle fracturePhysico-chemical / Chemical FailureMaterial Selection FactorsMedical Device SterilizationMedical Device SterilizationMedical Device SterilizationMedical Device SterilizationEffects of SterilizationEffects of SterilizationEvolution of Biomaterials
2_Medical Devices Overview.pdfMedical DevicesWhat Is a Medical Device?Definition of a Medical Device�(by US FDA)Classification of Medical Devices�(by US FDA)Classification of Medical Devices�(by US FDA)Classification of Medical Devices�(by US FDA)Classification of Medical Devices�(by US FDA)Getting a Device to MarketSubstantial EquivalencePremarket ApprovalCardiac Rhythm DisordersSpinal ConditionsCardiovascular DiseasesNeurological DisordersUrological and Digestive DisordersDiabetesCombination ProductsRecently Approved� Combination ProductsExtra SlidesDefinition of a Medical Device�(by EU)Classification of Medical Devices�(by EU)
3_Valves.pdfHeart ValvesProsthetic Heart ValveHeart�and�Heart�ValvesWhen is it used?Type of Prosthetic Heart ValvesMechanical Heart ValvesMechanical Heart ValvesBiological Heart ValvesBiological Heart ValvesMaterials in Mechanical Heart ValvesYield Strength to Density RatioPyrolytic CarbonPyrolytic CarbonPyrolytic CarbonPET and PTFEMaterials in Biological Heart ValvesPercutaneous ValvesWhat Does it Take �to Get a Surgical Valve to Market?Pre-Clinical Hydrodynamic TestPre-Clinical Structural TestPre-Clinical In Vivo Testing