L7: Synthetic biomaterials Flashcards
What are the 3 material properties?
- Material - mechanical properties, surface chemistry, degradation.
- Microstructure - fiber diameter, pore size.
- Activation - bioactive coating, incorporation of bioactive molecules.
In a study they seeded fibers for a blood vessel graft with MCP-1. What is the result?
MCP-1 have better collagen alignment & they produced more elastin.
(MCP-1 is added and this is released within hours but after months, the result is determined by this.
What is the difference in result if you put IL-4 or INF-y on a peripheral nerve conduct?
IL-4 > M2 > functional regeneration > good result.
IFN-y > M1 > not a good result.
What are the 2 major risk factors for implants?
- (material-induced) Thrombosis
- Implant-associated infections
How does the body prevent thromus formation in tissues?
Endothelial cells form a barrier between the blood and the rest.
Name 3 strategies to prevent thrombus formation and explain how it works.
- Inhibiting thrombin and/or fibrin formation > anti-coagulation.
Heparin immobilization: interferes in the cascade of coagulation. Inactivation of IXa, Xa, and thrombin.
Thrombomodulin immobilization: activates plasma protein C. This inactivates factors Va, VIIIa, and thrombin generation. - Inhibiting platelet activation > anti-platelet.
They mimic endothelial cells They stay close together so that the endothelial is not exposed. It doesn’t do anything with the coagulation cascade. Immobilization/ release of antiplatelet drugs (aspirin, prostaglandins, and prostacyclin). Nitric Oxide (NO) releasing/ generating materials. - Inhibiting protein/ cell adhesion > anti-fouling.
It prevents any protein adhesion. People make ‘invisible materials’ with Zwitterionic polymers. A layer of water if formed on top of the surface (super hydrophilic). It is energetically unfavorable for molecules to bind. So: water binding increases > protein adsorption decreased > platelet activation decreases (no clotting). However, if you block thrombosis formation, there is also no degeneration.
There is a variation in infection incidence with implants. What causes this variation?
- Site of application
- External: no surgical wound, no port d’entree
- Transcutaneous: surgical wound and port d’entree
- Implanted: surgical wound, no port d’entree - Biomaterial characteristics (texture/ topography, surface chemistry, etc.)
Why are implant infections hard to treat with antibiotics?
This is due to slime = biofilm = polysacharide intercellular adhesion (PIA). This consists of sugar molecules in which bacteria cover themselfves.
Steps of biofilm formation.
- Single free-floating bacteria attach to the surface (still reversible adhesion).
- Bacterial cells aggregate, ECM formation (slime). From now irreversible adhesion.
- Growth and division of bacteria for microcolony formation > multi-layered cells.
- Mature biofilm formation > ‘mushroom’ polysaccharides.
- Part of biofilm disperses to release free-floating bacteria for further colonization.
What is quorum sensing?
The gene expression by bacteria in the biofilm are regulated by quorum sensing. They tell each other what to do and every cell follow. As a result they produce extracellular polysacharides.
How can you compare the biofilm to the Hooligan concept?
- Commensial bacteria may turn into patogens (hooligans) A minimal amount is present. They copy each other.
- They form biofilms (in the biofilm they are protected, mass of hooligans). This should actually be prevented.
- Most of the time immunity (police) will control them.
- But when immunity is compromised, they may find other niches.
- And will cause problems in the surrounding area (throwing chairs), particularly when they take over immune cells.
What are antimicrobial strategies?
- Antimicrobial drug release - high concentration locally, can be ‘on-demand’, but temporary action (limited reservoir).
- Contact-killing: covalent linking of anti-microbial compound via flexible hydrophobic polymeric chains (permanent action).