Introduction to Biomaterials

BN3301 Introduction to Biomaterials Semester 1, 2013-2014

Lecturers: Zhang Yong (biezy@nus.edu.sg) Li Jun (bielj@nus.edu.sg)

Introduction to Biomaterials

Synthetic Biomaterials
Prehistory Romans, Chinese and Aztecs used gold in dentistry more than 2000 years ago, Glass eyes and wooden teeth have also been in common use through much of recorded history Late 1800s, improved aseptic techniques enabled some control over implant-related infections Early 1900s use of aluminium plates to cover skull defects, use of natural rubbers and celluloid, use of PTFE (Teflon) for cardiac valves and vascular grafts 1939 Polyethylene (PE) introduced for plastic surgery Silicone elastomers began use during world war 2 1947 Poly(methyl methacrylate) (PMMA) bone cement first use 1958 Polyvinyl chloride (PVC) introduced for heart assist pumps

Introduction to Biomaterials

Synthetic Biomaterials
About 50 years of formal clinical history, originally driven by resourceful and entrepreneurial hero surgeons 50s Biocompatible polymers developed 60s, 70s Urgency to address immediate patient needs and get devices into clinical use asap 80s Cleaned up commodity materials used extensively Lycra, Teflon, Polythene, GoreTex, Silastic, Dacron etc Growing Biomaterials research community Biomaterials Crisis Early 90s Increased litigation $$$$$$$$$ Large companies such as Dow and Du-Pont withdraw medical-grade materials Tightening of regulations Food and Drug Administration (FDA)

Rigorous long-term clinical testing of new biomaterials not performed

Introduction to Biomaterials

Biomaterials Famous Failures

Dow Silicone gel breast implants Polyesterurethane foam breast implants Bjork-Sheilly heart valves UHMWPE wear liners on hip/ knee prostheses wear particles Telectronics pacemaker J lead design Hip implants, cast versus forged, fracture and fatigue Why

The success of a biomaterial is highly dependent on three major factors: (1) the properties and biocompatibility of the implant (2) the health condition of the recipient (3) the competency of the surgeon who implants and monitors its progress

Introduction to Biomaterials

Biomaterials Famous Successes

In many instances, these traditional biomaterials have stood the test of time very well Cobalt-Chrome and Ti alloys used in orthopedics/ arthroplasty Medical grade stainless steel Various biodegradable sutures, pins etc Dacron fibre large bore vascular grafts UHMWPE wear liners on hip/ knee prostheses (when done properly!) UHMWPE still the best Silicone elastomer great biomaterial used in the right situation Hard grades of polyether-based polyurethanes

Introduction to Biomaterials

First Generation Biomaterials

Ad-hoc biomaterials Specified by physicians using common and borrowed materials Most successes were accidental rather than by design Examples: Gold fillings, wooden teeth, PMMA dental prosthesis Steel, gold, ivory, etc., bone plates Glass eyes and other body parts Dacron and parachute cloth vascular implants

Introduction to Biomaterials

Second Generation Biomaterials

Engineered implants using common and borrowed materials Developed through collaborations of physicians and engineers Built on first generation experiences Used advances in materials science (from other fields) Examples: Titanium alloy dental and orthopaedic implants Cobalt-chromium-molybdinum orthopaedic implants UHMW polyethylene bearing surfaces for total joint replacements Heart valves and pacemakers

Introduction to Biomaterials

Third Generation Biomaterials

Bioengineered implants using bioengineered materials Few examples on the market Examples: Tissue engineered implants designed to regrow rather than replace tissues Integra LifeSciences artificial skin Some resorbable bone repair cements Genetically engineered biological components

Introduction to Biomaterials

Biomaterials Development
Late 90s New biomaterials generation Large R&D funding injection Opportunities for improved formulations Materials engineered from ground up Material-physiological interface studied more extensively Much tighter control of manufacture (GLP/ GMP protocols necessary) Tissue Engineering field is born and continues to define itself

Introduction to Biomaterials

Biomaterials Development
New Millennium Exciting Possibilities! Growing understanding at the cellular and molecular level of Biocompatibility Biomimetics mimicing the brilliance and elegance of nature (spider silk, sea urchin spines, bone, coral fish teeth etc) Nanotechnology, nanostructured biomaterials, bottom up self assembly, nanomaterials used for gene delivery etc Hybrid artificial organs synthetic/ natural combinations >> TE Intelligent materials, shape memory, shrink, swell in response to environment Teamwork between many disciplines no boundaries

Introduction to Biomaterials

What are biomaterials?

Definition of a biomaterial (Greco, 1994) A biomaterial is "any substance (other than drugs) or combination of substances synthetic or natural in origin, which can be used for any period of time, as a whole or as a part of a system which treats, augments, or replaces any tissue, organ, or function of the body". = Biological materials?
Fields of knowledge to develop biomaterials Discipline Science and engineering Biology and physiology Clinical sciences Examples Material sciences: structure-property relationship of synthetic and biological materials including metals, ceramics, polymers, composites, tissues (blood and connective tissues), etc. Cell and molecular biology, animal and human physiology, immunology, etc.

All the clinical specialties: orthopedics, dentistry, neurosurgery, ophthalmology, cardiovascular surgery, etc.

Material Scientists + Chemists Bioengineers Immunologists + Biologists Surgeons

Introduction to Biomaterials

Existing Orthopedic Grafts

Biological Grafts
Autografts Allografts Xenografts

Synthetic Grafts
Synthetic materials

Autograft is the clinically preferred material for orthopedic repair, However, Autografts are - limited in supply - associated with donor site morbidity - suffer from structural constraints Limitations in existing grafts have prompted interest in tissue engineering

Introduction to Biomaterials

Synthetic Biomaterials
Organ/Tissue Examples heart eye ear bone pacemaker, artificial valve, artificial heart contact lens, intraocular lens artificial stapes, cochlea implant bone plate, intramedullary rod, joint prosthesis, bone cement, bone defect repair dialysis machine catheter and stent sutures, muscle stimulator artificial blood vessels burn dressings, artificial skin encapsulated pancreatic islet cells

kidney bladder muscle circulation skin endocrine

Introduction to Biomaterials

Biomaterials & applications

Journal of Materials Education Vol.21 (5-6): 297 - 306 (1999)

Introduction to Biomaterials

A few examples

Introduction to Biomaterials

Artificial Hip Joints

Hip replacement (total hip replacement), is a surgical procedure in which the hip joint is replaced by a prosthetic implant

Introduction to Biomaterials

Intraocular Lens

An intraocular lens (IOL) is an implanted lens in the eye, usually replacing the existing crystalline lens because it has been clouded over by a cataract, or as a form of refractive surgery to change the eye's optical power. IOLs are traditionally made of an inflexible material PMMA.

Introduction to Biomaterials

Vascular Grafts

A vascular graft is a man-made tube which replaces or bypasses part of a blood vessel, most commonly an artery

Introduction to Biomaterials

Artificial Heart Valves

A heart valve normally allows blood to flow through it in only one direction. There are four in a heart and they determine the pathway of blood flow through the heart. An artificial heart valve is a device implanted in the heart of a patient with heart valvular disease

Introduction to Biomaterials

Global Biomaterials Market

Total sales 1987 (M$4,700)

Total sales estimated for 2002 (M$ 11,700)

Journal of Materials Education Vol.21 (5-6): 297 - 306 (1999)

Introduction to Biomaterials

Global Biomaterials Market

Intraocular lenses (IOLs) >7,000,000/yr (PMMA, silicone) Hip and knee Prostheses >600,000/yr (titanium, steel, PE) Vascular Grafts >300,000/yr (Teflon, Dacron) Heart Valves >200,000/yr (carbon, fixed tissue) Percutaneous Devices >100,000/yr (titanium, silicone) Stimulatory Electrodes >100,000/yr (platinum, iridium) Catheters millions/yr (silicone, PVC, PEU, Teflon) Stents >2,500,000/yr (stainless steel) U.S. healthcare market (1998) > $1 trillion Millions of lives saved / The quality of life improved for millions more

Introduction to Biomaterials

Unit prices for several biomaterials and implants

Journal of Materials Education Vol.21 (5-6): 297 - 306 (1999)

Introduction to Biomaterials

Polymers as Biomaterials

Introduction to Biomaterials

Polymers as Biomaterials
Applications
Ear & ear parts: acrylic, polyethylene, silicone, poly(vinyl chloride) (PVC) Dentures: acrylic, ultrahigh molecular weight polyethylene (UHMWPE), epoxy Facial prosthesis: acrylic, PVC, polyurethane (PUR) Tracheal tubes: acrylic, silicone, nylon Heart & heart components: polyester, silicone, PVC Heart pacemaker: polyethylene, acetal Lung, kidney & liver parts: polyester, polyaldehyde, PVC Esophagus segments: polyethylene, polypropylene (PP), PVCDentures: acrylic, ultrahigh molecular weight polyethylene (UHMWPE), epoxy Blood vessels: PVC, polyester Biodegradable sutures: PUR Gastrointestinal segments: silicones, PVC, nylon Finger joints: silicone, UHMWPE Bones & joints: acrylic, nylon, silicone, PUR, PP, UHMWPE Knee joints: polyethylene

Introduction to Biomaterials

Polymers as Biomaterials
Biodegradable Polymers
Polymers designed to breakdown under certain conditions, can be cleavage of either chains, crosslinks, or both. Main advantage is no need to remove after use. Classes
Surface erodible, polyanhidrides, Polyorthoesters Bulk degradable, Polyesters, Polyamides, Polycarbonates, Phosphonitrilics Enzyme degradable, Polyesters, Polycarbonates, Natural polymers (proteins, polysaccharides) Covalently bound drug conjugates (pH sensitive), Polyacrylates, methacrylates, Carbohydrates

Introduction to Biomaterials

Polymers as Biomaterials
Biodegradable Polymers
Poly (-hydroxy acids) eg PLA, PGA
Have been in use clinically since 1970 Sutures, orthopedic pins, Drug delivery, screws etc Increasingly used as porous tissue engineering scaffolds Hydrolysis (brings MW down to 5000 Da), followed by degradation and resorption by cells Degradation rate can be controlled by manipulating MW, exposed surface area, crystallinity, and ratios of different monomeric units Readily molded, extruded, cast etc into fibres, meshes, films, tubes and matrices Acidic degradation products combined with fast degradation rates have caused some clinical problems due to a delayed inflammatory reaction that sometimes occurs Buffering with basic components (eg calcium phosphates)

Introduction to Biomaterials

Polymers as Biomaterials
Biodegradable Polymers
Poly (- caprolactone) PCL
Aliphatic polyester Used as biodegradable packaging material Capronor material recently FDA approved (1-year implantable contraceptive device) Low Tg (-62C) and Tm (57C) Undergoes hydrolytic degradation Significantly slower degradation than PGA or PLA Successfully copolymerised with lactic acid etc to soften and toughen them up

Introduction to Biomaterials

Polymers as Biomaterials
Biodegradable Polymers
Chitin / Chitosan
Natural aminopolysaccharide-biopolymer which is the major structural component of the exoskeleton of crabs, shrimps, lobsters, insects and cell walls of fungi. 1. Grind crab/shrimp shell 2. Remove mineral matter using hydrochloric acid 3. Remove protein component using dilute sodium hydroxide CHITIN 4. Deacetylate chitin using hot concentrated sodium hydroxide (This step effectively removes any residual proteins and endotoxins). 5. Rinse, dry CHITOSAN

Introduction to Biomaterials

Polymers as Biomaterials
Biodegradable Polymers
Applications Temporary scaffold Mechanical support Temporary grafts or stents Bone fixation (screws, plates) Wound repair or healing (Sutures, Adhesives) Slow transfer of stresses and forces Cell and tissue guidance (Cartilage, Nerve) Drug delivery Implanted systems are by design temporary Engineered to control release rate Multifunctional devices (Both mechanical and drug delivery functions)

Introduction to Biomaterials

Polymers as Biomaterials
Questions
Necessary chemical, physical and mechanical properties for proposed function Biocompatibility and biodegradability (change with time) Can polymer be fabricated without changing desirable properties (surface change, crystallinity and structure change) Sterilization (polymer may degrade and release toxic chemicals)

Introduction to Biomaterials

Metals as biomaterials
11 million people in US have implant (1988) 3.6 million orthopaedic surgeries/year in US, 4 out of top 10 involve metal devices (hard tissue replacement such as total hip and knee joints, fracture healing aids as bone plates and screws, dental implants) Properties and fabrication well known Joining technologies known Good mechanical properties: Stiff and strong Excellent electrical and thermal conductivity Bioinert

Introduction to Biomaterials

Metals as biomaterials

Applications Bone replacement Bone repair Artificial knee and hip joints Metal plates for fractures, etc. Screws and staples Dental implants (fillings and posts) Parts of other devices (Artificial hearts, Pacemakers, Catheters)

Introduction to Biomaterials

Metals as biomaterials
Types of metals Stainless steels (high carbon content causes corrosion of iron, high chromium content reduces strength, nickel added to increase strength) Titanium based alloys (very light but with high strength) Noble metals (Au, Pt, Pd, expensive and poor material properties, highly corrosion resistant)

Introduction to Biomaterials

Metals as biomaterials
Corrosion Mechanism (lowest energy state is oxidized state) Biological fluids contain water, dissolved oxygen, ions, etc, corrosive Metals degrade to oxides, hydroxides and other compounds Corrosion and fatigue can be synergistic effects Corrosion is one of most important aspects of metal biocompatibility

Introduction to Biomaterials

Ceramics & glasses

Ceramics can be defined as inorganic, non-metallic materials that are typically produced using clays and other minerals from the earth or chemically processed powders. Ceramics are typically crystalline in nature and are compounds formed between metallic and non-metallic elements such as aluminium and oxygen (alumina- Al2O3 ), silicon and nitrogen (silicon nitride- Si3N4), and silicon and carbon (silicon carbideSiC). Glass is often considered a subset of ceramics. Glass is somewhat different than ceramics in that it is amorphous, or has no long range crystalline order. Glass-ceramic is a type of glass formed by adding a nucleating agent to standard glass and then heating it until it crystallizes.

Introduction to Biomaterials

Ceramics & glasses

Glass: Amorphous, atoms are arranged without long term order The opposite of amorphous materials is a crystalline material Crystalline materials have some periodic crystal structure that results in long term order

Introduction to Biomaterials

Ceramics & glasses as biomaterials

Calcium phosphates Hydroxyapatite [HAp Ca10(PO4)6(OH)], can be powders, small dense implants, coatings and porous implants Bioactive glasses SiO2-P2O5-CaO-Na2O (surface forms a carbonated hydroxyapatite-HA layer)

Applications
Implants (used to replace skeletal hard connective tissues) Ceramics used in dentistry for dentures and crowns Porous carriers for biomolecules (Naturally inert and chemically resistant)

Introduction to Biomaterials

Weight % for enamel, dentine, bone and synthetic HAp

Introduction to Biomaterials

Ceramics & glasses as biomaterials

Drill a hole with reamer appropriate to dimensions of the selected implant at location of extraction site

View of temporary abutment after the healing period (about 10 weeks)

Temporary abutment removal after healing period, Implant is fully osseointegrated

Insert permanent abutment with integrated crown into the well of the implant

Introduction to Biomaterials

Composites as biomaterials
Consist of two or more distinct parts Have a distinct interface between materials Usually consist of matrix and reinforcement Matrix polymer, ceramic, metal Reinforcement fibers & particulates Specifications properties of materials, geometry of reinforcement, concentration, distribution, orientation

Introduction to Biomaterials

Composites as biomaterials
Composites Carbon fiber (biocompatible, reinforces polymer and ceramic systems, surface coating of orthopedic implants, tendon and ligament replacement) Polymer fiber (generally not high strength, exceptions: Kevlar and UHMWPE, similar apps as carbon, PLA, PGA, and PGLA reinforce degradable polymers) Ceramics (weak in tension or shear, brittle, usually a particulate in other materials) Glasses (fiber glass reinforces polymers, good mechanical and electrical properties, resorbable glasses in resorbable polymers)

Introduction to Biomaterials

Composites as biomaterials

Introduction to Biomaterials

Composites as biomaterials

Introduction to Biomaterials

Composites as biomaterials

Introduction to Biomaterials

Composites as biomaterials

Introduction to Biomaterials

Bionic Man National Geographic (Dec 89)

What materials are mentioned here? Silicone Titanium described as biocompatible metal mandibular mesh Gore-tex (teflon fabric) Stainless steel, and cobalt-chrome-moly alloy, platinum Polythene Dacron (polyester fibre) and PMMA (perspex/ acrylic) Polyurethane Zirconia ceramic Absorbable plastic pins (PLA or PGA?) Composites Artificial (silicone) ear, covered by a skin graft. Will the tissue survive?