Biomaterial transformation and translocation

Question 1

Outline the tissue response to biomaterials.

Answer 1

• • The biggest concern is that wear debris particles will form due to the implant’s presence.
• • The host response to wear particles will determine the clinical consequence of the implant.
• • Examples:-
    1. Cobalt chromium (metal on metal implants) – releases chromium 6 phosphate which are genotoxic.
    2. Ceramic implants – lead to excessive calcium release and loading, which can cause cell death. However more inert than metal implants.
• • Concerns over implant risk to foetus in pregnant women.
• • Different materials have different rates of wear – e.g. metal on metal will have a lower rate of wear than metal on polymer implants.
• • This will lead to an immune response against nanoparticles and tissue damage leading to failure of the implant.
• • The fact that nanoparticle has very different properties from bulk material is why we need to find more thorough studies reactivity/toxicity of nanoparticles used in biomaterials.

Question 2

Describe the implant-failure cascade.

Answer 2

1. When the two surfaces are not truly flat, their outgrowths (called asperities) will deform leading to more contact and friction between the two surfaces leading to formation of wear particles.
2. Wear involves loss of material in a particulate form due to motion between two surfaces under load.
3. The wear particles formed at the articulate joint (by surfaces moving against each other) can induce immune reaction –> leading to chronic inflammation which prevents healing.
4. The particles can be ingested by macrophages and lead to release of ROS which recruits assembly of the inflammasome.
5. Inflammatory cytokines are released to recruit other immune cells to site of implant.
6. Wound healing will lead to fibrous encapsulation – the interface of the implant will be surrounded by fibroblasts – that has macrophages etc, the capsule will try to shield the implant from healthy bone as a protective measure.
7. There is formation of foreign giant body cells from macrophages (multinucleated cells MNGCs) joining together after attempt to get rid of the wear particles leading to chronic inflammation (due to release of inflammatory mediators) as they aren’t able to remove them. MGNCs are formed if one macrophage can’t remove the biomaterial as it’s too large.
8. They can be 100s of nuclei large and are present in body for up to years – difficult to remove.
9. All of the inflammation will lead to tissue damage (necrosis) and production of bone resorbing factors such as collagenase – the much weaker bone will lead to a higher load placed on implant so the implant will fail.

Question 3

Outline the history and concerns over metal-metal hip replacements.

Answer 3

a. One third of implants in the US are metal on metal (MOM) implants. However they have early, higher failure rates – especially cobalt chromium, which has early failure from unexplained pain.
b. This is due to the poor biocompatibility and release of the genotoxic cobalt 2+ and chromium 6+ ions. The exact mechanism is still unknown. There’s currently projects to find out.
c. Multiple studies have shown chronic elevations of cobalt and chromium ions in serum following implant.
d. There are concerns over release of chemically active metal ions which can bind to proteins and disseminate all over the body,
e. EDX analysis from TEM of a cobalt chromium implant shows that cobalt particles are corroding – shown by near absence of cobalt in most areas. Since the material is 60% Co, how does it get out?
i. Could be due to corrosion in synovial fluid and particles diffusing into tissue but still unknown.
f. Implications for long term health as Co2+ damages DNA and Cr6+ is a carcinogen.

Question 4

Outline use of hydroxyapatite implants.

Answer 4

a. Despite great potential of HA in bone grafting – used to coat implants, there’s concern over their long term fate.
b. Problem of wear particles being released after implantation – the wear particles were feared to chip off and cause bone resorption by inflammation.
c. Studies have shown in acidic environments, the HA will dissolve releasing Ca2+ - high levels of calcium can lead to tissue necrosis.
d. In macrophages –> the nanoparticles can leave lysosomes in cell after calcium release and disperse all over the ER and cross the nuclear membrane of macrophage into its nucleus – cytotoxic, leading to cell death and loss of viability.
e. This can be exploited – the HA can be used as a vehicle to deliver drugs to the nucleus