When does a material become a
biomaterial?
Prof. Dr. Ir. Jan Van Humbeeck
MTM-K.U.Leuven 1
When it is allowed making
contact with human tissue
2
The goal of using biomaterials:
Assisting in
• Regenerating
• Repairing
• Supporting
• Replacing
defect tissues and esthetic parts.
3
Origin of defects in the body
• Life quality: – congenital defects
– development defects
– diseases
– accidents
– aesthetic reasons
• Tissue degeneration due to aging: – Osteoporosis
– Hart failure
– Wear of joints
4
A problem of aging
Czech expression:
If you’re over 60 and wake up one morning and nothing hurts,
then you’re probably dead. 5
What is a biomaterial?
• A biomaterial is a nonviable material used in a (medical) device, intended to interact with biological systems (biofunctionality). (Williams, 1987)
• A biomaterial is a material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body.
• A biomaterial is a material that should perform an intended function over a definite amount of time in a specific biological environment, as good as possible.
• Biomaterials are inorganic or organic materials that are biocompatible and can be implanted in the human body to replace or repair failing tissue.
6
History of biomaterials
• 1° generation-materials: based on replacing tissue or replacing a function with as low as possible interaction with the surrounding tissue. Those materials were found in the classic industrial markets. Those materials were selected because of their corrosion resistance or inertness when in contact with a tissue.
• metals: SS, Ti, Co-Cr
• polymers: UHMWPE, PMMA, PMDS
• ceramics: Al2O3
7
A false toe made of out of wood and leather
was found on a 3,000-year-old
mummified body of an Egyptian noblewoman
Cripple with supporting pole.
Italian vase, 4 BC. The Louvre.
Teeth were extracted from the dead to make
dentures, so many got collected after battles, and
in her time known as Waterloo Teeth.
The desperately poor also sold their teeth.
Real teeth were considered the best replacement
for people who had lost their own.
(19th century)
Did Georg Washingthon
had a wooden set of teeth?
8
• 2° generation-materials: one searches for and develops
specific biomaterials that can be bioactive and
stimulate tissue repair or tissue growth.
– metals: SMA, new beta-Ti alloys, porous materials
– polymers: biodegradable
– ceramics: bioactive glass, hydroxyapatiet
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• 3° generation-materials: tissue engineering.
- Regenerative biomaterials in combination with living
cells
- Biological active materials
- Transformation in and formation of new tissue (i.e.
osteoinductive material).
10
Different kinds of biomaterialen
I. Inorganic biomaterials
• Bio-tolerated materials: reactions between tissue and material are possible but should not be harmful (i.e. Incapsulation)
• Bio-inactive or bio-inert materials: do not show reaction with the tissue
• Bio-active materials should stimulate tissue repair and/or growth
II. Organic biomaterials: • Collagen, (demineralised ) bone, hart valves from pigs,
transplants (auto-, allo-, xenograften)
• polymers
III. Combinations of inorganic en organic biomaterials
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The classes of materials
• Metals
• Ceramics
• Inorganic glasses
• Polymers
• Composites
• Natural biomaterials
12
13
Metals
• Metallic bounding in lattice structures
• High E-modulus
• Good strength
• Good ductility (plasticity)
• Few metals are biocompatible (non-toxic)
14
Ceramics
• Anorganic components (oxides, nitrides,
carbides, ..) with a combination of ionic and
covalent binding
• Complex crystal lattice or amorphous
• (Generally) High E-modulus
• Brittle especially under tensile loading
• (relative) inert or very biodegradable
15
Inorganic glass
• Closepacked but disordered structure
• Often network structures (silicates,
phosphates, bio-active glass, ..)
16
Polymers
• Chain structures with covalent bindings
(especially C)
• Van der Waals and H-bridges between the
chains
• Amorphous or semi-crystalline
• Low E-modulus
• Enormous variability also within each class
17
Composites
• Combination of two or more materials from
the preceding families
• Properties can be adapted by appropriate
volume fractions and distribution of the
different materials
18
Natural biomaterials
• Proteins: – Silk
– Collagen
– Keratin
– …
• Polysaccharide: – Cellulose (cotton, wood))
– Chitin
– Chitosan
– …
• Auto-, Allo-, Xenografts – Species dependent
– Tissue dependent
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The biological environment
• At one hand side: the biological environment is
very aggressive : high chemical activity with
large variation in combination with a large
spectrum of mechanical forces
• At the other hand side: the biological
environment is very constant concerning
physical conditions and the composition of the
environment as a consequence of a complex
control system
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The biological environment
Consequence: Inflammation or infection
The local reaction of a tissue due to a harmful stimulus : the stimulus can be physical, chemical or immunological (foreign body reaction) or can be a consequence of the presence of micro-organisms (bacteria's, viruses, parasites, …)
Solution:
- usage of bio-inert materials
- within a timeframe usage of medicine to avoid (limit) inflammation or infection
- sterilisation of the implant
- medication attached to the implant (i.e. DES: Drug Eluting Stent)
- usage of antibiotics
21
Table
22
Element Requirement mg/day Selected Biochemical
function
Distribution in various
body parts
Cobalt (Co) 0.14-1.77 Methionine metabolism Myocardium and bones
Chromium (Cr) 0.005-0.2 Binding of insulin to cells,
glucose metabolism
Lungs, liver, Carbohydrate
lipid metabolism
Copper (Cu) 2-6 Hemoglobin synthesis, bone
development
Blood, bone, brain, muscles,
skin, liver, intestine and
kidney
Iron (Fe) 8-18 Oxygen transport Liver, spleen and blood
Lithium (Li) 0.06-0.07 Pharmacological action Tissues, brain, endocrine
and exocrine glands
Magnesium (Mg) 200-400 Activator for enzymes,
Physical stability of DNA
Bones, soft tissues, blood,
chromosomes, Ribosomes
Manganese (Mn) 0.5-5 Oxidative phosphorylation,
Cholesterol metabolism
Mitochondria, liver, kidney,
pancreas
Molybdenum (Mo) 0.048-0.1 Xanthine metabolism Dental enamel, bones,
intestine, liver and kidney
Zinc (Zn) 8-15 Nucleic acid and protein
synthesis
Liver, prostrate, voluntary
muscles
Element Deficiency Disorders
Cobalt (Co) Anemia, B12 deficiency Cardiomyopathy
Goiter
Chromium (Cr) Impairment of glucose
tolerance
Renal failure
Pulmonary cancer
Copper (Cu) Anemia, growth retardation,
changes in aortic elastin
Hepatitis, Cirrhosis,
Tremor
Iron (Fe) Anemia
Hepatic failure
Diabetes
Arthritis
Lithium (Li) Manic depressive disorders Unknown
Magnesium (Mg) Renal failure, Alcoholism
Hallucination,
Depression,
Spasmophilia
Manganese (Mn) Bleeding disorder Parkinson like syndrome
Molybdenum (Mo) Esophageal cancer Hyperuricemia
Zinc (Zn)
Growth retardation,
Psychological disturbances,
Gonad atrophy
Gastric ulcer,
Respiratory distress
Data related to essential trace elements Disorders of Essential metal metabolism in humans
23
Element Tolerance levels (µg/day) Distribution in various body
parts
Diseases caused by Excess
amounts
Arsenic (As) 40-70 Skin, Hair, Tissues, Nail
Nausea, Vomiting, Diarrhea,
Pigmentation of fingers and nails,
Burning of mouth and throat,
Prostration and weakness
Chromium (Cr)+6 5-200 Lungs, Liver, Carbohydrate and
Lipid metabolism
Hyperglycemia, Skin cancer,
Lung cancer, Impair growth,
Hypocholestremia
Mercury (Hg) 10-20 Kidney, Skin, Hair, nail
Tremor, Diarrhea, Myocardial
necrosis, Fetotoxicity,
Proteinuria
Antimony (Sb) 9-11.3 Tissues Nausea, Vomiting, Diarrhea,
Weakness
Selenium (Se) 130-200 Liver, Skin, Muscle, Kidney
Loss of hair, Lassitude,
Depression, Dermatitis, Alcopia
tumor
Lead (Pb) 20-280 Red blood cells, Liver, Kidney,
Skeleton
Sterility, Neonatal mortality and
morbidity, Kidney damage,
Effects nervous system
Cadmium (Cd) 10-50 Mollusks, Kidney, Tissues Kidney damage, Skeletal
damage, Pulmonary damage
Data related to toxic elements
24
Requirements of a biomaterial
1. Biocompatibility: Biocompatibility is the ability of a material to perform with an appropriate host response in a specific application (Williams, 1987)
It refers in fact to the aspects concerning the absence of toxicity, immunogenicity, carcinogenicity and thrombogenicity
2. Biofunctionality: Simulating the function as good as possible
Load bearing (mechanical, physical, chemical) Articulating (low wear and few wear debris) Keeping the blood running Filling the volumes Creating electrical stimuli Stimulation of the regeneration of tissue, …. Sterilizable, storable and resorbable
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3. Mechanocompatibility: The stress on an implant should be preferably in the same order as the stress exerted on the environmental tissue to avoid the problem of “stress shielding”.
4. Biostability: A biomaterial will be either permanent either temporally either biodegradable.
5. Reliability, reproducibility or individually adapted.
26
Factors playing a role in
biocompatibility
• Problem:
– Difference between tissue (living) and the material (dead)
– The material of the implant in contact with the tissue creates a “foreign body reaction”
27
Factors playing a role in biocompatibility
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Factors playing a role in
biocompatibility Procedural definition: ISO 10993-1
“ A system or material that is in accordance with the following
requirements is considered biocompatible”
(tested according FDA of CE-norms).
•Satisfy the conditions of animal welfare
•testing genotoxicity, carcenogenicity
•reproducible toxicity
•Blood interactions
•in vitro cytotoxicity
•local effects after implantation
•EO sterilisation residues
•Material degradation
•irritation and sensitivity (allergy)
•Sample preparation
•systemic toxicity
•identification en quantification of degradation products
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Host response
• Species dependent (animal experiments do
not give always the same response as a
human being)
• Age dependent
• Health dependent
• immunologic/metabolic system dependent
• Dependent on surgeon and care
30
Complications due to the presence of an
implant (1)
• Deposition of cellular tissue:
– Proteins
– Macrophages
– Fibrous tissue
– Formation of a biofilm (micro-colonies of
bacteria's)
31
Foreign body response
• Rapid dilation of cappilarities, increased
permeability of endothelial cell linings and
cell reactions
• Macrophages release degadative enzymes
(lysozymes) that attempt to digest the
foreign material
• Macrophages multiply (Mitosis) and serve
as progenitor to the giant cell
• Undisgestable: frustrated phagocytosis 32
33
Complications due to the presence of an
implant (2)
• Changed stress conditions (stress shielding): i.e. when the
stress on bone surrounding the implant will be very low it
can lead to bone-necrosis which can lead to loosening of
the implant.
• Reliability: failing of the implant on long term due to
material degradation
34
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A biomaterial
– interacts with living tissue (selection in function of
toxicity for surrounding tissue)
– is time dependent (selection in function of the time of
functioning (i.e. degradation of function))
– is place dependent (selection in function of chemical
and mechanical properties of the surrounding tissue)
– is function dependent (selection in function of mainly
mechanical performance of the material)
Conclusion
Applications of biomaterials
According to the problem:
Problem Example
-replacement of ill or damaged part Hip prosthesis, hart valves
-assistance of healing sutures, plasters, bone plates, stents
-Improvement of a function
Pacemaker, contact lenses
-Cosmetic problems Breast protheses, artificial skin
-tools for diagnosis
Catheters, sensors
-tools for trearments Catheters, drug release systems
37
According to the system
• Musculoskeletal
• Dental and maxillofacial
• Cardiovascular
• Organs and skin
• Sensors
Applications of biomaterials
38
Some examples on the more
than 50 different types of implants
The bionic woman
39
Examples Musculoskeletal :
•hip-prostheses
•finger-
•knee-
•Hip screws
•nails
•Bone plates
•…
Cardiovascular:
•pacemaker
•stents
•artificial arteries or veins
•Hart valves
•…
Dental en Maxillofacial
•Tooth implants
•Skull plates and hooks
•orthodontic parts
•…
Organs :
•skin
•Breast prostheses
•Kidney dialysis
•Artificial hart
•urinary (i.e. stoma)
•…
Sensors:
•cochlear
•intra-ocular and contact lenses)
•…
Others:
•exoprostheses (Ilizarov)
•Artificial nails
•Plasters and sutures
•catheters
•… 40
Musculoskeletal
• Hip-prostheses
• Finger-
• Knee-
• Hip screws
• Nails
• Bone plates …
41
• Total Hip Prosthesis (THP)
42
Finger prosthesis
43
Knee prostheses
44
Elbow prosthesis
45
Foot prosthesis
46
Spina prosthesis
47
Healing of bone fractures
48
49
Cardiovascular
• Pacemaker
• Stents
• artificial arteries or veins
• Hart valves
• …..
50
Pacemaker
51
Atrial (or ventricular) septal defect
Amplatzer
54
Hart valves Not in use anymore
Present
55
Dental and maxillofacial
• Tooth implants
• Skull plates and hooks
• orthodontic devices
• …
56
Tooth implants
57
maxillofacial
59
Organs
• skin
• Breast prostheses
• Kidney dialysis
• Artificial hart
• urinary (i.e. stoma)
• …
60
Artificial skin
61
Breast prosthesis
62
Kidney dialysis
63
stoma, incontinence
65
Sensors
• cochlear
• intra-ocular and contact lenses
• …
66
Ear implants
67
Others
• Exoprosthesen (Ilizarov)
• Artificial nails
• Plasters and sutures
• Catheters
• …
69
Planned surgical procedure included nail exraction, medulary canal reaming,
nailing with a longer nail locked proximally, then fitting of a monolateral external
lenghtening device to lenghten over the nail. At the end the nail is locked
distally and the exfix is discarded.
Ilizarov fixator
70
Medical instruments
Technical tools 72
Skin care
Ear stops Artificial nails
73