professor david williams - university of technology sydney · essential biomaterials science:...

Essential Biomaterials Science

Professor David Williams Adjunct Professor, University of Technology, Sydney

Professor, Wake Forest Institute of Regenerative Medicine, USA Chairman, Strait Access Technologies Pty, Ltd, South Africa

Partner, Morgan & Masterson LLC, USA Immediate Global Past-President, TERMIS

Professor Emeritus, University of Liverpool, UK

Visiting Professor Universities in Cape Town, Shanghai, Beijing, Taipei

Seminar at University of Technology, Sydney, Australia 19th April 2016

Essential Biomaterials Science: Professor David Williams

Biomaterials-based statistics (1) In the USA, 138,000 hip replacements were performed in 2001.

By 2010, the number was 310,000 There was a 92% increase in patients over 75

But a 205% increase in those aged 45-54. 16% of USA adults (20 million people) live with chronic kidney disease

600,000 patients are treated by haemodialysis, but life expectancy is 5 years 100,000 on transplant waiting list, 16,000 performed a year, but far more cost effective

Wound care market globally is US$ 17 billion Of which the market for wound dressings is US$ 10 billion

85,000 adults implanted with aortic valve replacements in the US 45,000 patients globally receive TAVI treatment at $30,000 per valve

20 million Americans suffer from cataracts 3 million receive IOLs per year at $3,500 per procedure

98% successful

Essential Biomaterials Science: Professor David Williams Biomaterials-based statistics (2)

One-third of women under 60 years have some symptoms of Stress Urinary Incontinence, One half for those over 60 years -

no fully satisfactory treatment yet For diabetic patients, the market for human insulin is US$ 20 billion

Need better (biomaterials-based) delivery systems Deep brain stimulators for treatment of Parkinson’s disease now relatively successful.

With market size of over US$ 1 billion Gene therapy market, in early stage of development expected to be US$ 11 billion by

2020; need safe non-viral, biomaterials-based vectors Imaging contrast agent market already at US$ 4 billion, expected to grow with newer

nanomaterials systems Annual world-wide sales of cochlear implants 50,000 Australian company Cochlear has 53% market share

160,000 implants would be needed annually to treat all children who have severe-profound sensorineural hearing loss


q Applications and performance specifications for biomaterials

q Classification of biomaterials q Biocompatibility pathways

q Biomaterials in medical devices q Biomaterials in regenerative medicine q Biomaterials in drug and gene delivery

q Biomaterials in imaging systems q Future perspectives


Applications and Performance Specifications for Biomaterials

•  What is a biomaterial ?

•  What are biomaterials used for? •  What are the essential characteristics of

biomaterials? •  How do we define their performance specifications?

The Classification of Biomaterials Applications (1)

Class 1 Permanent (Long-term) Implantable Devices

Class 1.1 Permanent implantable devices for the anatomical replacement of parts of the body that have undergone some form

of degenerative disease. Class 1.2 Permanent implantable devices for the anatomical

replacement of parts of the body that have undergone surgical removal of cancerous tissue.

Class 1.3 Permanent implantable devices for the correction of congenital or developmental deformities.

Class 1.4 Permanent implantable devices for the restoration or correction of function after injury.

Class 1.5 Permanent implantable devices for the restoration or correction of function as a consequence of disease.

Class 1.6 Permanent implantable devices for cosmetic purposes.

The Classification of Biomaterials Applications (2)

Class 2 Short-term Implantable Devices

Class 2.1 Implantable devices to assist in the repair of broken bones Class 2.2 Implantable devices to assist in the repair of soft tissue

Class 3 Invasive but Removable Devices

Class 3.1 Indwelling catheters and shunts

Class 3.2 Contraceptive devices

Class 4 External Artificial Organs / Organ Assist devices

Class 4.1 Devices attached to the patient that deliver short-term support Class 4.2 Devices attached to the patient that act as a bridge to transplant or life-long

support

Class 5 Surgical and Clinical Accessories

Class 5.1 Wound dressings Class 5.2 Short-term catheters and drains

The Classification of Biomaterials Applications (3) Class 6 Drug and Gene Delivery Systems

Class 6.1 Oral drug delivery systems Class 6.2 Infusion systems

Class 6.3 Systems for delivery across epithelial / mucosal surfaces Class 6.4 Monolithic implantable devices

Class 6.5 Microparticulate and nanoparticulate systems Class 6.6 Prodrugs and polymer therapeutics

Class 6.7 Anti-microbial systems Class 6.8 Immunotherapy and chemotherapy hybrids

Class 6.9 Non-viral gene vectors Class 6.10 Engineered viral vectors Class 6.11 Vaccine delivery systems

Class 6.12 Theranostic systems Class 7 Tissue Engineering Systems

Class 7.1 Engineered cell therapy products for regenerative medicine purposes Class 7.2 Engineered gene therapy products for regenerative medicine purposes

Class 7.3 Ex vivo / bioreactor generated tissue constructs Class 7.4 Cell seeded implanted scaffolds

Class 7.5 Cell-free implanted scaffolds Class 7.6 Injectable cell seeded products

Class 7.7 Injectable cell-free products Class 7.8 Cell sheet engineered constructs

Class 7.9 Engineered systems for drug discovery and testing Class 7.10 Engineered tumor models Class 8 In Vivo Diagnostic Systems

Class 8.1 MRI contrast agents Class 8.2 Ultrasound contrast agents

Class 8.3 Fluorescence and bioluminescene imaging systems Class 8.4 Contrast enhanced micro CT systems

Class 8.5 Implantable biosensors

The Baseline Biomaterial Configuration: The material is a single-phase, isotropic, homogeneous,

chemically-defined substance Interaction 1

There is a thermodynamically-driven adsorption of tissue components onto the material surface; components of blood, extracellular fluid, urine, saliva, tears etc immediately attach themselves to the biomaterial surface.

Interaction 2

The tissue responds to the presence of the material; a non-specific response of the body to invasion by a foreign object, mediated by size, shape and surface characteristics.

Interaction 3

The tissue responds to the physical characteristics of the material; biophysical processes influence the relationship between the biomaterial surface and the tissues.

Interaction 4

The tissue and material interact mechanically; mechanical forces significantly influence the development of the longer term response from the tissue and its components and also the response of the material to these

components.

Interaction 5 The material responds to the fluid tissue environment; the time dependent response of the material to the

aggressive tissue fluids, where deviations from the baseline biomaterial configuration (such as the presence of complex microstructures and additives / contaminants) start to influence the material response, either beneficially

or deleteriously.

Interaction 6 The tissue responds to the chemical nature of the material and any released components; this is the ultimate

determinant of the performance and safety of the biomaterial, and is significantly influenced by compositional and structural deviations from the simple, baseline configuration.

The Generic Requirements for Biomaterials (1) Functionality; optional, depending on application

General Volume, size, shape, surface characteristics Mechanical Elasticity / rigidity, strength / fracture

resistance Tribological properties (wear, friction) Stress transfer to cells / tissues

Physical Electrical properties Thermal properties Optical / optoelectronic properties Magnetic properties

Chemical Control of biostability / biodegradation Biological and Pharmacological

Control of cell phenotype Control of molecular targeting Pharmacokinetics / pharmacodynamics

The Generic Requirements for Biomaterials (2) Safety; Mandatory

Intrinsic Biocompatibility Appropriate local host response,

Control of cytotoxicity Absence of remote or systemic adverse effects

Clinical Application Technique sensitivity

Patient sensitivity

Practical Features; Variable importance

Supply Suitability for quality manufacturing Sterilization and infection control

Economics Acceptable costs of goods

Appropriate business models Regulatory Absence of insurmountable hurdles Ethical Absence of insurmountable hurdles


Classification of Biomaterials Principles of classification First Level of Classification

•  The metallic systems •  The ceramic systems

•  The polymeric systems •  Carbon materials

•  Composite materials •  Engineered biological materials

The Second Level of the Classification of Biomaterials; Metallic Systems

Class 1.1 Titanium and Titanium Alloys Class 1.1.1 Commercially Pure Titanium

Class 1.1.2 Alpha and Near Alpha Titanium Alloys Class 1.1.3 Alpha-beta Alloys

Class 1.1.3.1 Titanium – 6% Aluminum -4% Vanadium Class 1.1.3.2 Titanium -6% Aluminum – 7% Niobium

Class 1.1.4 Beta Titanium Alloys

Class 1.2 Iron and Steels Class 1.2.1 Austenitic Stainless Steels

Class 1.2.1.1 ASTM 316 and 316L Austenitic Stainless Steel Class 1.2.1.2 High Nitrogen / Low Nickel Austenitic Stainless Steel

Class 1.2.2 Ferritic and Duplex Steels Class 1.2.3 Iron Nanowires

Class 1.3 Cobalt based Alloys

Class 1.3.1 Cobalt-Chromium-Molybdenum Alloys Class 1.3.2 Cobalt-Chromium –Tungsten-Nickel Alloys Class 1.3.3 Cobalt-Chromium-Iron-Nickel-Molybdenum

Class 1.3.4 Cobalt-Nickel-Chromium-Molybdenum Alloys

The Second Level of the Classification of Biomaterials; Metallic Systems

Class 1.4 Nickel Based Alloys Class 1.4.1 Nickel-Titanium Shape Memory Alloy

Class 1.5 Tantalum and Zirconium Alloys

Class 1.5.1 Porous Unalloyed Tantalum Class 1.5.2 Zirconium-Niobium Alloys and Oxidized Zirconium Alloys

Class 1.6 Silver

Class 1.6.1 Silver Coatings Class 1.6.2 Silver Electrodes

Class 1.6.3 Nanocrystalline Silver and Silver Nanoparticles

Class 1.7 Platinum Group Metals and Alloys Class 1.7.1 Platinum and its Alloys

Class 1.7.1.1 Platinum - Iridium alloys Class 1.7.2 Palladium-based Alloys

Class 1.7.3 Iridium Films

Class 1.8 Gold Class 1.8.1 Metallic Gold

Class 1.8.2 Gold Nanoparticles

Class 1.9 Magnesium and its Alloys

The Second Level of the Classification of Biomaterials; Ceramic Systems Class 2.1 Oxides

Class 2.1.1 Aluminum Oxide (Alumina) Class 2.1.2 Zirconium Oxide (Zirconia)

Class 2.1.2.1 Partially Stabilized Zirconia Class 2.1.2.2. Stabilized Zirconia; Tetragonal Zirconia Polycrystals

Class 2.1.3 Alumina – Zirconia Ceramics Class 2.1.4 Silicon Oxides (Silica)

Class 2.1.4.1 Crystalline and Non-crystalline Silica Class 2.1.4.2 Mesoporous Silica and Silica-based Nanoparticles

Class 2.1.5 Titanium Oxides Class 2.1.6 Iron Oxide Nanoparticles

Class 2.1.7 Iridium Oxide Class 2.1.8 Cerium Oxide

The Second Level of the Classification of Biomaterials; Ceramic Systems Class 2.2 Phosphates

Class 2.2.1 Amorphous Calcium Phosphates Class 2.2.2 Monocalcium Phosphates

Class 2.2.3 Dicalcium Phosphates Class 2.2.4 Tricalcium Phosphates

Class 2.2.5 Octacalcium Phosphates Class 2.2.6 Hydroxyapatite

Class 2.2.7 Biphasic Calcium Phosphates Class 2.2.8 Calcium Phosphate Cements

Class 2.2.8.1 Apatite Calcium Phosphate Cements Class 2.2.8.2 Brushite Calcium Phosphate Cements

Class 2.3 Sulfates

Class 2.3.1 Calcium Sulfates

Class 2.4 Silicates and Silica-based Glasses Class 2.4.1 Wollastonite

Class 2.4.2 Diopside and Akermanite Class 2.4.3 Zeolites; Aluminosilicates

Class 2.4.4 Silica-based Glasses; Bioactive Glasses

Class 2.5 Nitrides

Class 2.6 Carbides

Class 2.7 Titanates

Class 2.8 Optically Active Ceramic / Metallic Nanoparticles Class 2.8.1 Semiconductor Quantum Dots

Class 2.8.2 Rare Earth Upconverting Nanoparticles

The Second Level of the Classification of Biomaterials; Polymeric Systems

Class 3.1 Thermoplastic Polymers

Class 3.1.1 Polyolefins Class 3.1.1.1 Polyethylene

Class 3.1.1.1.1 Low Density Polyethylene Class 3.1.1.1.2 High Density Polyethylene

Class 3.1.1.2 Polypropylene Class 3.1.1.3 Polymethylpenetene (TPX)

Class 3.1.2 Fluorinated Hydrocarbon (Fluorocarbon) Polymers Class 3.1.2.1 Polytetrafluoroethylene Class 3.1.2.2 Polyvinylidine fluoride

Class 3.1.2.3 Perfluorocarbons Class 3.1.3 Acrylic Polymers

Class 3.1.3.1 Acrylic Acid Based Materials Class 3.1.3.2 Methacrylic Acid Based Materials

Class 3.1.4 Polyaryletherketones Class 3.1.4.1 Poly(aryl-ether-ether-ketone), PEEK

Class 3.1.4.2 Carbon –fiber Reinforced PEEK Class 3.1.5 Polysulfones and Polyethersulfones

Class 3.1.6 Polycarbonates Class 3.1.7 Polyimides

Class 3.1.8 Polyurethanes Class 3.1.9 Polyacetals


Class 3.2 Thermosetting Resins Class 3.2.1 Epoxy Systems

Class 3.3 Synthetic Polymeric Sols and Gels

Class 3.3.1 Polyethylene glycol / Polyethylene oxide Class 3.3.2 Pluronics

Class 3.3.3 Polyhydroxyethymethacrylate Class 3.3.4 Poly(vinyl alcohol)

Class 3.3.5 Polyglycerols Class 3.3.6 Inverted Colloid Crystals

Class 3.4 Proteins and Peptides Class 3.4.1 Collagen Derivatives

Class 3.4.1.1 Gelatin Class 3.4.2 Elastin Derivatives

Class 3.4.3 Resilin Class 3.4.4 Fibrin Derivatives

Class 3.4.5 Laminin Derivatives Class 3.4.6 Silk

Class 3.4.7 Keratins Class 3.4.8 Zein

Class 3.4.9 Peptide Nanomaterials Class 3.4.10 Protein and Peptide Mimetics


Class 3.5 Polysaccharides Class 3.5.1 Hyaluronan Derivatives

Class 3.5.2 Alginates Class 3.5.3 Chitin and its Derivatives

Class 3.5.4 Pullulan Class 3.5.5 Dextran Polymers

Class 3.5.6 Cellulose Class 3.5.6.1 Microbial Cellulose Class 3.5.6.2 Methylcellulose and

Carboxymethylcellulose

Class 3.6; Lipids Class 3.6.1 Phospholipids

Class 3.6.2 Liposomes


Class 3.7 Biodegradable Structural Polymers Class 3.7.1 The Poly (α –hydroxy acids);

Polylactides and Polyglycolides Class 3.7.2 Polycaprolactone Class 3.7.3 Polydioxanone

Class 3.7.4 Poly(ortho esters) Class 3.7.5 Polyanhydrides

Class 3.7.6 Polyketals Class 3.7.7 Sebacate Polymers Class 3.7.8 Fumarate Polymers

Class 3.7.9 Cyanoacrylate Polymers Class 3.7.10 Degradable Polyurethanes

Class 3.7.11 Polyhydroxyalkanoates

The Second Level of the Classification of Biomaterials; Polymeric Systems Class 3.8 Water Soluble Polymers

Class 3.8.1; Polyethylenimine Class 3.8.2 Hydroxypropyl methacrylamide

Class 3.8.3 Polyvinylpyrrolidone Class 3.8.4 Polyamidoamines

Class 3.9 Polymers with Ionisable or Ionic Groups

Class 3.9.1 Conducting Polymers Class 3.9.1.1 Polypyrrole

Class 3.9.2 Polyelectrolytes

Class 3.10 Elastomers Class 3.10 1 Silicone Elastomers

Class 3.10 2 Polyurethane Elastomers Class 3.10.3 Poly(styrene-block-isobutylene-block-styrene):(SIBS)

Class 3.10.4 Plasticized Polyvinylchloride

Class 3.11 Fibers, Fabrics and Textiles Class 3.11.1 Polyethylene Terephthalate Materials

Class 3.11.2 Microporous Expanded Polytetrafluoroethylene

Class 3.12 Environmentally Responsive Polymers Class 3.12.1 Thermo-responsive Polymers

Class 3.12.2 pH Responsive Polymers

The Second Level of the Classification of Biomaterials; Carbon Biomaterials

Class 4.1 Diamond and Diamond-like Materials Class 4.1.1 Diamond-like Carbon

Class 4.1.2 Tetrahedral Amorphous Carbon Class 4.1.3 Nanocrystalline and Ultrananocrystalline Diamond

Class 4.2 Graphitic Materials Class 4.2.1 Pyrolytic Carbon

Class 4.2.2 Activated Charcoal

Class 4.3 Glassy or Vitreous Carbon

Class 4.4 Hexagonally Bonded Carbon Nanostructures Class 4.4.1 Fullerenes

Class 4.4.2 Carbon Nanotubes Class 4.4.3 Graphene

The Second Level of the Classification of Biomaterials; Composite Biomaterials

Class 5.1 Fiber Reinforced Thermoplastic Polymers

Class 5.2 Fiber Reinforced Resins

Class 5.3 Ceramic Microparticle / Biostable

Polymers

Class 5.4 Ceramic Microparticle / Biodegradable Polymers

Class 5.5 Nanocomposites

The Second Level of the Classification of Biomaterials;

Engineered Biological Materials Class 6.1 Autologous Tissues

Class 6.2 Allogeneic Tissues Class 6.2.1 Allograft Bone

Class 6.2.2 Allograft Cartilage Class 6.2.3 Allograft Dermis

Class 6.2.4 Allograft Blood Vessels Class 6.2.5 Allograft Amniotic Membrane

Class 6.2.6 Allograft Dura Mater Class 6.2.7 Allograft Fascia Lata

Class 6.3 Xenogeneic Tissues Class 6.3.1 Xenogeneic Bone

Class 6.3.2 Xenogeneic Small Intestine Submucosa Class 6.3.3 Xenogeneic Pericardium

Class 6.3.4 Xenogeneic Aortic Valve Tissue Class 6.3.5 Xenogeneic Whole Organs

professor david williams - university of technology sydney · essential biomaterials science:...

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