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 Did Georg Washingthon A false toe made of out of wood and leather had a wooden set of teeth? 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) 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 Data related to essential trace elements Disorders of Essential metal metabolism in humans

Selected Biochemical Distribution in various Element Requirement mg/day function body parts Element Deficiency Disorders

Cobalt (Co) 0.14-1.77 Methionine metabolism Myocardium and bones Cardiomyopathy Cobalt (Co) Anemia, B deficiency 12 Goiter

Binding of insulin to cells, Lungs, liver, Carbohydrate Impairment of glucose Renal failure Chromium (Cr) 0.005-0.2 Chromium (Cr) glucose metabolism lipid metabolism tolerance Pulmonary cancer

Blood, bone, brain, muscles, Hemoglobin synthesis, bone Anemia, growth retardation, Hepatitis, Cirrhosis, Copper (Cu) 2-6 skin, liver, intestine and development Copper (Cu) kidney changes in aortic elastin Tremor

Iron (Fe) 8-18 Oxygen transport Liver, spleen and blood Hepatic failure Iron (Fe) Anemia Diabetes Arthritis Tissues, brain, endocrine Lithium (Li) 0.06-0.07 Pharmacological action and exocrine glands Lithium (Li) Manic depressive disorders Unknown

Activator for enzymes, Bones, soft tissues, blood, Magnesium (Mg) 200-400 Physical stability of DNA chromosomes, Ribosomes Hallucination, Magnesium (Mg) Renal failure, Alcoholism Depression, Spasmophilia Oxidative phosphorylation, Mitochondria, liver, kidney, Manganese (Mn) 0.5-5 Cholesterol metabolism pancreas Manganese (Mn) Bleeding disorder Parkinson like syndrome Molybdenum (Mo) Esophageal cancer Hyperuricemia Dental enamel, bones, Molybdenum (Mo) 0.048-0.1 Xanthine metabolism intestine, liver and kidney Growth retardation, Gastric ulcer, Zinc (Zn) Psychological disturbances, Nucleic acid and protein Liver, prostrate, voluntary Respiratory distress Zinc (Zn) 8-15 synthesis muscles Gonad atrophy

23 Data related to toxic elements

Distribution in various body Diseases caused by Excess Element Tolerance levels (µg/day) parts amounts

Nausea, Vomiting, Diarrhea, Pigmentation of fingers and nails, Arsenic (As) 40-70 Skin, Hair, Tissues, Nail Burning of mouth and throat, Prostration and weakness

Hyperglycemia, Skin cancer, Lungs, Liver, Carbohydrate and Chromium (Cr)+6 5-200 Lung cancer, Impair growth, Lipid metabolism Hypocholestremia

Tremor, Diarrhea, Myocardial Mercury (Hg) 10-20 Kidney, Skin, Hair, nail necrosis, Fetotoxicity, Proteinuria

Nausea, Vomiting, Diarrhea, Antimony (Sb) 9-11.3 Tissues Weakness

Loss of hair, Lassitude, Selenium (Se) 130-200 Liver, Skin, Muscle, Kidney Depression, Dermatitis, Alcopia tumor

Sterility, Neonatal mortality and Red blood cells, Liver, Kidney, Lead (Pb) 20-280 morbidity, Kidney damage, Skeleton Effects nervous system

Kidney damage, Skeletal Cadmium (Cd) 10-50 Mollusks, Kidney, Tissues damage, Pulmonary damage

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 Conclusion 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) 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 Applications of biomaterials

According to the system

• Musculoskeletal

• Dental and maxillofacial

• Cardiovascular

• Organs and skin

• Sensors

38 Some examples on the more than 50 different types of implants

The bionic woman

39 Examples Musculoskeletal : •hip-prostheses Organs : •finger- •skin •knee- •Breast prostheses •Hip screws •Kidney dialysis •nails •Artificial hart •Bone plates •urinary (i.e. stoma) •… •…

Cardiovascular: Sensors: •pacemaker •cochlear •stents •intra-ocular and contact lenses) •artificial arteries or veins •… •Hart valves •… Others: •exoprostheses (Ilizarov) Dental en Maxillofacial •Artificial nails •Tooth implants •Plasters and sutures •Skull plates and hooks •catheters •orthodontic parts •… 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 Not in use anymore Hart valves

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 Artificial nails Ear stops

Skin care

73