Biomaterials in Medical Devices - Tor VergataIssues of Biomaterials in Medical Devices. 15/40 • Understanding and controlling performance – Physical, Chemical, Biological ... between

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

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Introduction

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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.

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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

6/40

– 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

8/40

– 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

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

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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

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

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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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• 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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• 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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• 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

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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

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

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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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• 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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• 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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• 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)

√

√

√

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


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


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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)


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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


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


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

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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

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

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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.

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)

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Heart Valves

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 doesn’t close properly and blood leaks backward

9/30

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– 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

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 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

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)

19/30

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 H’s replaced with F’s– 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 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.

30/30

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

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 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

Biomaterials in Medical Devices - Tor VergataIssues of Biomaterials in Medical Devices. 15/40 • Understanding and controlling performance – Physical, Chemical, Biological ... between

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