L5 + L6: Natural biomaterials Flashcards
Give 3 examples of naturally-derived materials and 3 of synthetic materials.
Naturally-derived materials:
1. ECM components (e.g. silk, fibrin, heparin, etc.)
2. Decellularized native tissues
3. Lab-grown tissues (TE)
Synthetic materials:
1. Ceramic implants
2. Metalic implants
3. Non-degradable plastics
Pros and cons of naturally-derived materials
Pros:
* Native ligands landscape & ligans presentation (!)
* Inherent bioactivity (!)
* Ability to host efficiently degrade & remodel
Cons:
* Typically rapidly degraded
* Can be antigenic
* Biologic variability
* Limited mechanical properties
* Limited control
* Processing (you cannot just implant it, you need to process it, e.g. sterilize)
Pros and cons of synthetic materials
Pros:
* Fully tailorable
* Mechanically strong
* Processing (you can control a lot)
* No donor issue needed
Cons:
* No inherent ligands for cells
* No inherent growth factors
* No efficient degradation & remodeling by cells
Allograft =
Xenograft =
Allograft= from another human.
Xenograft= from different species.
Why decellularization?
It is necessary to remove the cellular components that elicit adverse host response/ to prevent immune reaction by the adaptive system. You want to remove antigens.
What is important when choosing a decellularization method?
The best method depends on the tissue!
Methods: physical (flushing with detergents or freezing), chemical, detergent-based, or enzymatic.
* All methods cause collateral damage to the ECM!
Decellularization is a trade-off between … and …?
Cell removal and tissue preservation.
(so: taking as many cellular remnants out vs limiting damage to the tissue).
What components are still left after decellularization that have an effect on the host response?
- DNA remnamts & fragments; elicit adverse effects above a certain threshold.
- DAMPs; lysis your cells (dood van de cell door het breken van het membraan).
- Antigens
What are the two types of (hyper) acute xenograft rejection?
Humoral (natural present antibodies) & cellular
How does an acute humor rejection occur?
The cell has a certain antigen (alpha-Gal) and this binds to the antibody in your body. By binding, the cells can recognize it. Complement proteins can bind to 2 antibodies and cross-link them. This creates a response: formation of MAC. This forms a hole in the cell and it will die.
How does a cellular rejection occur?
Antibodies activating your cells. ‘on signal’. Your own cells have a way of inhibiting your immune system. Your own cells present SLA-I. Then, the NK cells know not to kill your own cells. You have CD47 and this connects to alpha.
Difference alpha-Gal and anti-Gal
a-Gal: carbohydrate (sugar molecule), found in all mammals, but not in humans and specific monkeys. The a-Gal epitope can remain present in decell. tissue (depending on the processing method).
Anti-Gal: antibodies against the a-Gal epitope produced after exposure by activated B cells. Found in humans (the most abundant natural antibody in humans).
Cross-linking=
Masking remaining cellular epitopes in decell. tissue. Groups are made unavailable for cells; they cannot bind.
3 (negative) side effects of cross-linking
Slows down/ prevents tissue degradation
Mask inherent bioactivity & ligands
Prevents cell infiltration (leads to dead tissue)
In a study they compared two grafts. One was cross-linked and one was not cross-linked. What is the effect of (chemical) cross-linking?
Cross-linked: scar tissue
(cell influx and vascularization less and later & multinucleated giant cells > FBR).
Not cross-linked: functional tissue regeneration
(fast cell infiltration, faster degradation, no FBR).
