Biomaterials in Medical Devices
Eunsung Park, Ph.D.Medtronic Strategy and Innovation
Medtronic, [email protected]
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
1/40
Introduction
2/40
Materials Science and Engineering
Transparent Plane??!@!
3/40
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.
4/40
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
5/40
MIT OCW
6/40
Stainless Steel Ti and alloys Co alloys NiTi Pt-Ir, Ta Au
Metallic Biomaterials
7/40
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
8/40
Pyrolytic carbon, Diamond-like carbon Alumina, Zirconia Hydroxyapatite / Calcium phosphates Bioglasses A/W glass-ceramic
BioCeramics
9/40
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
10/40
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
11/40
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
12/40
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
15/40
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.
Contd
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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:
17/40
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
18/40
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
20/40
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
21/40
In Vivo Tests
Relevant mammalian model
Comprehensive biological response
Ethical concerns
Expensive & time-consuming
22/40
Clinical Trials
Most relevant test
Safety and efficacy test
All other tests measured against this
Expensive, logistically complicated
Difficult to interpret results
23/40
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 dont 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
29/40
Fractography: brittle fracture
Mirror
Mist
Hackle
http://www.doitpoms.ac.uk/tlplib/fracture/images/glass2.gif
30/40
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
39/40
Evolution of Biomaterials
Structural
Functional Tissue Engineering Constructs
Soft Tissue Replacements
40/40
Progression of Biomaterials Technologies: Compatibility
1960s
Biostability
DurabilityTolerance by body
1980s
Biocompatibility
Blood and tissue compatibility
Bio-Interactivity
Living implants Modification of cells
2000
1/26
Medical Devices
2/26
What Is a Medical Device?
What is not?
3/26
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
4/26
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?
5/26
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
6/26
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
7/26
Classification of Medical Devices(by US FDA)
Class III: General controls and Premarket Approval Premarket approval, scientific reviews to ensure
the devices safety and effectiveness
Life-supporting or life-sustaining devices
Less than 10% of all devices are Class III
Heart valves, pacemakers, breast implants, stents
8/26
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.
9/26
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
10/26
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
11/26
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)
12/26
Diagnostic Devices
Determine the cause of disease or injury Examples
Imaging (X-ray, CT, MRI) DNA-base diagnostics; POC devices Cardiac marker-base diagnostics
13/26
Monitoring Devices
Determine the progress of therapy and the state of the patient in response to therapy
Examples Blood pressure ECG Blood oxygen monitor
14/26
Therapeutic Devices
Change structure and function of the biological system to alter the course of disease
Examples Pacemakers Stents Spinal fixation devices
15/26
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)
Implantable Therapeutic Medical Devices for Chronic Diseases
Most Advanced Technologies=
16/26
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
17/26
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
18/26
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
19/26
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
20/26
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
21/26
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
22/26
Bio-Materials Technologypast, present, future
BIOmaterials
time
bioMATERIALS
BIOMATERIALS
23/26
Drugs
Biologics
Devices
Combin
ation
Combination
Com
bin a
ti on
Drugs
Biologics
Devices
Combination Products
24/26
Antibiotic bone cement and orthopedic implants
Steroid eluting pacemaker
Lumbar fusion device with growth factor
Drug eluting stents
Combination Products
25/26
Recently ApprovedCombination Products
Transdermal patch for treatment of Parkinsons 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
26/26
Miniaturization and longevity
Improved sensors and diagnostics
Enhanced biomaterials
Better disease prevention
Better technologies
Traditional Medical
Technology
Biotechnology
Nanotechnology
Information technology
+
Innovative Medical Technology
1/30
Heart Valves
2/30
Prosthetic Heart Valve
A prosthetic (artificial) heart valve is a replacement for a diseased or dysfunctional heart valve.
3/30
Heartand
HeartValves
Right Atrium
Right Ventricle
Left Ventricle
Left Atrium
Pulmonary Vein Aorta
4/30
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)
5/30
Heart Valves
6/30
7/30
Mitral Valve
8/30
When is it used?
Two conditions that may require a heart valve replacement are Stenosis (smaller opening)
Leaflets thicken or stiffen
Regurgitation (incompetence) Valve doesnt 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
10/30
Mechanical Heart Valves Caged ball valve
Occluder in restraining cage 1960s 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
11/30
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.
13/30
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
14/30
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.)
15/30
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
16/30
CP Ti All -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
17/30
Yield Strength to Density Ratio
18/30
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
20/30Buddy Ratner, Introduction to Biomaterials
21/30
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
22/30
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
23/30
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
24/30
Allotropes of Carbon
Allotropes: structures with different molecular configurations
25/30
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 Hs replaced with Fs High melting (Tm=325C) polymer Very hydrophobic and lubricious catheter, graft Teflon
26/30
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
27/30
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
28/30
Percutaneous Valves
29/30
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 Assessmentbiocompatibility, 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.
30/30
Pre-Clinical Hydrodynamic Test
Hydrodynamic performance is compared with a clinically-approved reference valve Steady, Pulsatile Flow Pressure Drop
P vs. Q Steady, Pulsatile Flow Regurgitation and Leakage
Flow Visualization to assess flow patterns through valve
31/30
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
32/30
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 DevicesContdBiocompatibilityAssessing 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 ValveHeartandHeartValvesWhen 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
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