L5 + L6: Natural biomaterials

Question 1

Give 3 examples of naturally-derived materials and 3 of synthetic materials.

Answer 1

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

Question 2

Pros and cons of naturally-derived materials

Answer 2

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)

Question 3

Pros and cons of synthetic materials

Answer 3

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

Question 4

Allograft =
Xenograft =

Answer 4

Allograft= from another human.
Xenograft= from different species.

Question 5

Why decellularization?

Answer 5

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.

Question 6

What is important when choosing a decellularization method?

Answer 6

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!

Question 7

Decellularization is a trade-off between … and …?

Answer 7

Cell removal and tissue preservation.

(so: taking as many cellular remnants out vs limiting damage to the tissue).

Question 8

What components are still left after decellularization that have an effect on the host response?

Answer 8

• 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

Question 9

What are the two types of (hyper) acute xenograft rejection?

Answer 9

Humoral (natural present antibodies) & cellular

Question 10

How does an acute humor rejection occur?

Answer 10

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.

Question 11

How does a cellular rejection occur?

Answer 11

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.

Question 12

Difference alpha-Gal and anti-Gal

Answer 12

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).

Question 13

Cross-linking=

Answer 13

Masking remaining cellular epitopes in decell. tissue. Groups are made unavailable for cells; they cannot bind.

Question 14

3 (negative) side effects of cross-linking

Answer 14

Slows down/ prevents tissue degradation
Mask inherent bioactivity & ligands
Prevents cell infiltration (leads to dead tissue)

Question 15

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?

Answer 15

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).

Question 16

Every natural matrix evokes a unique host response depending on … and …

Answer 16

Source of tissues and processing methods.

Question 17

What are the advances of materials-driven in situ regeneration?

Answer 17

Readily available
Cose effective
Autogolous, living tissue

Question 18

What is the main challenge with resorbable synthetics?

Answer 18

Find a balance between tissue regeneration vs repair (scar formation).

Question 19

Polymer degradation depends on … and …

Answer 19

Cell influx & phenotype

Question 20

A lot of giant cells lead to less/a lot of degradation.

Answer 20

a lot of giant cells = a lot of degradation

Question 21

What are the two types of degradation of synthetic scaffolds?

Answer 21

Hydrolysis/ enzymatic
Oxidative

Question 22

Explain hydrolysis/ enzymatic degradation

Answer 22

Surface erosion!
Passive process. The material is still the same, but there is less of it. ‘You start chopping wood from the outside. Then you still have wood, but just less wood’. It becomes porous.

Question 23

Explain oxidative degradation

Answer 23

Polymer breakdown!
Molecular level changes. The material is broken down because the molecules inside change. This is really cell-dependent! The outside is often smooth.

Question 24

Why is it important to have a good degradation rate?

Answer 24

Too fast leads to loss of structural integrity.
Too slow leads to fibrosis.

Question 25

Give advantages of naturally-derived materials and synthetic materials.

Answer 25

Naturally-derived materals:
- Native ligand landscape
- Inherent bioactivity
- Ability of host to efficiently degrade & remodel

Synthetic materials:
- Fully tailorable
- Mechanically strong
- Processing
- No donor tissue needed
- Not antigentic