Nerves

Question 1

What does the PNS consist of?

Answer 1

Nerves and supporting cells outside the CNS.

Question 2

Describe the structure of a peripheral nerve.

Answer 2

Epineurium: The outermost layer providing mechanical support to the nerve.
Perineurium: Surrounds fascicles and acts as a blood-nerve barrier.
Endoneurium: Surrounds connective tissue around
individual axons and their Schwann cells, and supports
capillaries.

Question 3

What are the functions of Schwann cells?

Answer 3

Provide structural support for nerve fibres
Produce growth factors
Essential successful nerve regeneration

Question 4

What are the 3 steps of nerve regeneration?

Answer 4

Wallerian degeneration
Phagocytosis and reconstruction
Axonal regeneration and remyelination.

Question 5

What is Wallerian degeneration?

Answer 5

● Axonal breakdown
● Myelin sheath breaks up into debris
● Schwann cell de-differentiate

Question 6

What recruits macrophages to the injury site?

Answer 6

Cytokine signalling.

Question 7

Describe the process of phagocytosis and reconstruction in PN regeneration.

Answer 7

Macrophage recruitment
Macrophaes + Schwann cells phagocytose myelin/axonal debris
Schwann cells elongate to form Bands of Bungner

Question 8

Describe the process of axonal regeneration and remyelination in PN regeneration.

Answer 8

New axonal sprouts form from the proximal stump, guided by the Bands of Bungner towards their original endoneurial tubes.

Schwann cells differentiate back to the original phenotype and remyelinate the new axons.

Question 9

What is the first-line repair for gaps <10 mm?

Answer 9

Tension-free end-to-end nerve suture. Only for clean transection injury.

Question 10

What is the gold standard treatment for gaps up to 5 cm?

Answer 10

Nerve autograft.

Question 11

What are the pros and cons of nerve autografting?

Answer 11

Pros:
Autologous - No immunosuppressants
The most biocompatible (has correct ECM, GFs, and adhesion molecules)

Cons:
Limited supply of donor nerve
Donor site morbidity and requires second surgery

Question 12

What repair method is used for gaps >5 cm?

Answer 12

Nerve allograft (from a cadaver)

Question 13

What are the pros and cons of nerve allografts?

Answer 13

Pros:
Correct topography, guidance cues and mechanical properties of nerve.
Large supply, no donor deficit.
Same autograft surgical technique

Cons:
Cost
Immunosuppressants needed

Question 14

What are nerve xenografts/wraps made from?

Answer 14

Decellularised porcine small intestinal submucosa.

Question 15

What are the pros and cons of a nerve xenograft?

Answer 15

Pros:
Survives in a xenogenic host without immunologic consequences.
Good biomechanical support
Correct microenvironment.

Cons:
High cost
Variable immune responses and degradation rates
Risk of infectious disease transmission
Lack of available pre-clinical and clinical data exists

Question 16

What is a nerve guidance conduit, and what are its current limitations?

Answer 16

Cylinders used to entubulate cut nerves.
Limited regeneration distance and effectiveness of re-innervation.

Question 17

What are the ideal properties of a tissue engineered NGC?

Answer 17

Biocompatible

Biodegradable - mechanically stable during regeneration

Resist tear from sutures and tissue inflammation

Flexible and soft: prevents compression of regenerating axons

Provide guidance cues for extending growth cones

Semi-permeable: allows diffusion of nutrients and oxygen (pore size:10-20µm)

Prevents fibrous tissue ingrowth and retains neurotrophic factors

Ease of handling for surgeons

Sterilised appropriately without losing physical properties.

Question 18

What does intraluminal guidance involve?

Answer 18

Use of electrospun fibres inside the conduit to guide axon growth.

Question 19

What does 3D printing offer for NGC design?

Answer 19

Customisable internal architecture with high resolution.

Question 20

What are microchannels used for?

Answer 20

Mimic fascicle layout and provide directional guidance.

Question 21

What is the role of porosity in NGCs?

Answer 21

Enables diffusion but may allow scar tissue ingrowth.

Question 22

Name and explain two methods of surface modification.

Answer 22

Used to increase biocompatibility of the material by introducing bioactive functional groups or surface coating.

Plasma polymerisation
Surface hydrolysis
Plasma etching
Grafting
Silane modification.

Question 23

What are the advantages and disadvantages of natural coatings for NGCs?

Answer 23

Advantages:
○ Improve biocompatibility
○ Mimics ECM to provide correct topography

Disadvantages:
○ Batch variation
○ Undesirable immune responses
○ Expensive to manufacture

Question 24

What are the advantages of synthetic coatings for NGCs?

Answer 24

○ Reproducible
○ Cost-effective
○ Applied to degradable and non-degradable substrates in a scalable way
○ Control chemical group deposition at sub-micron scale and associated
topographical profiles

Question 25

Explain the limitations of plasma polymerisation

Answer 25

Plasma polymerisation: Costly, time consuming

Question 26

Name some neurotrophic GFs relevant to nerve TE and explain why they're useful.

Answer 26

NGF and BDNF Stimulate axonal growth and support Schwann cell function, and synergise well.

Question 27

What cell types are used in cell-based therapies?

Answer 27

Schwann cells, BMSCs, ASCs.

Question 28

What do BMSCs and ASCs contribute?

Answer 28

Secrete neurotrophic factors and support regeneration. Differentiate into neural and glial cell lineages.

Question 29

How can SCs be added to the NGC?

Answer 29

● Injection ● Suspension within a hydrogel, ● Intraluminal guidance structures ● Released from the luminal wall.

Question 30

List the researched methods to improve NGC technology.

Answer 30

Intraluminal guidance Micro-grooved luminal design Microchannels and porosity Surface functionalisation A combination of these approaches.

Question 31

List some commercial names of the FDA approved materials

Answer 31

Neuragen Reaxon Neuroflex Neurotube Neurolac

Question 32

What is NeuraGen made of?

Answer 32

Type I collagen (natural)

Question 33

What are the pros of Reaxon?

Answer 33

Made from chitosan; abundant and biocompatible.

Question 34

What is Neurolac composed of?

Answer 34

PDLCL (synthetic)

Question 35

Name a drawback of Neurotube (PLGA).

Answer 35

Degrades quickly; acidic byproducts.

Question 36

Name some synthetic polymers in research conduits.

Answer 36

PLLA, PCL, Polyhydroxyalkanoates.

Question 37

Name some natural research materials.

Answer 37

Silk, keratin, gelatin.

Question 38

What are the pros and cons of natural materials?

Answer 38

Pros: Topographical cues (cell adhesion molecules), superior biocompatibility Cons: Batch variability and poor mechanical strength.

Question 39

Explain why a decellularised nerve conduit may be superior to current approaches.

Answer 39

Allografts and xenografts have the correct topography, guidance cues and mechanical properties of nerve. But they require immunosuppression. Decellularisation removes immunogenic cellular constituents. This preserves the native ECM which enhances the regenerative capacity.