Lecture 3

Question 1

Biomaterials can release substances (leachables)

Answer 1

Polymers
- residual monomers
- oligomers
- catalysts
- processing aids
- additives
- contaminants
Metals and Ceramics
- ions
- oxydes

• chemicals formed after heat treatments, welding, sterilization, degradation…

Question 2

Toxicants

Answer 2

Man-made (synthetic) substances that possess potentially harmful or adverse properties for living organisms (humans in the medical context)

Question 3

Toxins

Answer 3

Toxic substances produced by living organisms.

Question 4

Toxicity

Answer 4

Toxicity is the degree to which a substance can damage an organism or a substructure of the organism, such as a cell (cytotoxicity) or an organ such as the liver (hepatotoxicity).

Question 5

Xenobiotics

Answer 5

Foreign material or substance found in the bod. To assess biomaterials biocompatibility, one must evaluate the potential toxicity of all the possible xenobiotics released in vivo.

Question 6

Different forms of toxicity

Answer 6

1. Toxicant can: remain in the implant site (local effect), be transported systemically (systemic effect
2. Toxicant can: alter the biological environment (causing general molecular, organelle, cellular or tissue/organ dysfunction), interact specifically with endogenous molecules (protein, membrane component, DNA,…)

Question 7

Response to a toxicant depends on:

Answer 7

• The material
- Chemical nature (esp. potential chemical
reactivity)
- Size/shape (e.g. bulk vs nanoparticle)
• The type of exposure
- Route(s) and site(s) (e.g. cutaneous vs
perfusion, brain vs skin)
- Duration (hours vs permanent)
- Frequency (continuous, daily, yearly…)
• The dose (dose-response relationship)

Question 8

The dose-response relationship

Answer 8

NOAEL: Not Observable Adverse Effect Level
(highest dose at which there is NO toxic effect)
LOAEL: Lowest Observable Adverse Effect Level
(lowest dose at which there is toxic effect)

Question 9

Mechanisms of cytotoxicity

Answer 9

• Local pH alteration
• Solvents/Detergents disturbing cell membranes
• Alteration of inter- and extra-cellular transport processes
• Chemicals facilitating aberrant protein phosphorylation
• Dysregulation of electrically excitable cells
• Disruption of mitochondrial function
• Damage of genetic information
• Mediation of inflammation and fibrosis
• Induction of cell necrosis or apoptosis

Question 10

Biomaterial/device toxicity can involve complex mechanisms, so

Answer 10

Worst-case scenarios must be considered. Example: Metal-on-Metal hip prosthetics. No short term problems observed, but long term lead to acidic environments and corrosion.

Question 11

Approaches to control/suppress the toxicity of a material.

Answer 11

• Modify material composition or processing
• Reduce the exposure time
• Reduce the dose/release rate
• Inhibit the mechanisms causing toxicity

Question 12

Cd2+ ions are toxic (released by CoSe in oxidative environment)

Answer 12

• Genotoxicity (binding to mitochondries, DNA fragmentation)
• Perturb cell membrane transport (toxic to heart tissue)
• Activate inflammation in liver (hepatotoxicity)

Question 13

Cytotoxicity assessment of CdSe QDs

Answer 13

Count cells, change medium, add QDs, rinse, count cells again. R= N(after)/N(before)

Question 14

Grafting PEG brushes leads to

Answer 14

reduction in cellular intake, does not

reduce intracellular toxicity