When does a material become a biomaterial? - · PDF fileWhen does a material become a biomaterial? Prof. Dr. Ir. Jan Van Humbeeck MTM-K.U.Leuven 1

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

9

• 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

11

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

19

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

20

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

25

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

28

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

29

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

35

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

Stents

52

Artificial arteries or veins

53

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

Orthodontic devices

58

maxillofacial

59

Organs

• skin

• Breast prostheses

• Kidney dialysis

• Artificial hart

• urinary (i.e. stoma)

• …

60

Artificial skin

61

Breast prosthesis

62

Kidney dialysis

63

Artificial hart

64

stoma, incontinence

65

Sensors

• cochlear

• intra-ocular and contact lenses

• …

66

Ear implants

67

Artificial eye lenses

68

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

Wound care

71

Medical instruments

Technical tools 72

Skin care

Ear stops Artificial nails

73