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
Essential Biomaterials Science: Professor David Williams
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
Essential Biomaterials Science: Professor David Williams
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
Essential Biomaterials Science: Professor David Williams
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
The Second Level of the Classification of Biomaterials; Polymeric Systems
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
The Second Level of the Classification of Biomaterials; Polymeric Systems
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
The Second Level of the Classification of Biomaterials; Polymeric Systems
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