Nerve

Question 1

What is the anatomy of peripheral nerve?

Answer 1

nerve trunk
endonerium
nerve fibre
motor neuron
sensory neuron

Question 2

How are sensory neurones and motor neurones linked?

Answer 2

1) sensory nerve from tendon organ
2) inhibitory interneuron
3) spinal cord
4) alpha motoneuron
5) muscle

Question 3

Does adult PNS have capacity for regeneration?

Answer 3

Yes
Many neurotrophic factors are known
Return of normal function is rare. Motor & sensory deficits common

Question 4

How does a peripheral nerve regenerate after injury?

Answer 4

1) Tip of nerve stump swells
2) Severed axons retract several mm
3) Proximal axons sprout vigorously after several days
4) Growth cones emerge from proximal axon along adhesive terrain
5) Growth cones elicit numerous extensions – fillapodia
6) Fillapodia extend outwards in all directions
7) The first fillapodium to reach an appropriate terrain survives
8) All other fillapodia die back
9) Distal nerve stump undergoes Wallerian 10) Degeneration (WD)
WD – axon degradation and
11) Schwann cell proliferation
13) Schwann cells organise in ordered columns
Columns referred to as bands of Büngner
Schwann cells provide optimal conditions for growth cone adhesion

Question 5

What are the three main clinical strategies to repair gap injuries?

Answer 5

1) Suturing together proximal and distal ends 
 \+ ‘Clean' transection injury 
 -   Tension in sutures
2) Autografting
\+ Good reinnervation 
-  Donor site morbidity
3.Nerve guidance conduits 
 \+ Biocompatible materials
 -  Primitive design 
 -  Limited regeneration

Question 6

Why is surgical repair necessary for neural regeneration?

Answer 6

• Negligible repair in absence of surgical reconnection
• Early surgical repair used crude materials
  Catgut, silk, cotton, metal wire
• Frequently failed due to poor sterilisation techniques and inadequate sterilisation of implanted material
• 1950 & 60s – Coaptation was refined (end-to-end repair)
  Surgical microscope, finer suture materials & instrumentation

Question 7

How is epineural repair carried out?

Answer 7

• Fine polyamide sutures are placed through the epineural connective tissue
• Important to avoid underlying nerve tissue

Question 8

How is facicular ot perineural repair carried out?

Answer 8

• Fine sutures are placed through the perineural connective tissue
• Significantly no better than epineural repair

Question 9

How are nerve autografts carried out surgically?

Answer 9

• Used when nerve retraction or loss prevents end-to-end repair
• Used when reapproximation causes tension along suture line
• Patient’s sural nerve is interposed between damaged ends

Question 10

What are the limitations of nerve autografts for injury repair?

Answer 10

Poor motor & sensory recovery
Limited nerve availability
Donor site co -morbidity

Question 11

What size does the nerve gap injury need to be to need a nerve autograft>

Answer 11

> 2cm

Question 12

What are examples of nerve guidance channels?

Answer 12

1) Integra Life Sciences NeuraGen™ nerve guide
=absorbable semi-permeable collagen tube
2) SaluMedica’s SaluBridge™ nerve cuff
=flexible tubular sheath made from silicone

Question 13

How do nerve guidance channels (NGC) lead to neural regeneration?

Answer 13

Cylinders used to entubulate cut nerves

1800s to 1950s saw use of bone, collagen membranes, arteries and veins
Limited clinical usage
Poor choice of materials provided no useful clinical benefit

WW I & II saw use of parchment paper, tantalum, magnesium, rubber and gelatin
Limited biocompatibility caused tissue inflammation / rejection

1980s to present
Use of biocompatible materials enables moderate regeneration

Question 14

What are the main characteristics of a conduit for nerve gap repair?

Answer 14

1) permissive microenvironment
2) bioresorbable
3) biocompatible
4) clinically applicable
5) beneficial to nerve regeneration

Question 15

What are the advantages of NGCs?

Answer 15

1) Surgical repair is simplified
2) Tension at suture line is reduced
3) Scar tissue invasion is prevented
4) Outgrowing tissue is guided
5) Endogenous neuroactive molecules are sequestered
6) External inhibitory molecules are repelled

Question 16

How are sciatic nerve model use in experimental neurology?

Answer 16

Cross-sectional area, number of myelinated axons, relative percentages of epineurium / endoneurium / blood vessels
Electrophysiology responses
Electromyographic responses
Reflex and sensory perception

Question 17

In NGCs, how does the biomaterial used influence nerve repair?

Answer 17

Transmural Permeability
Surface texture / Microgeometry
Electrical charge characteristics

Question 18

How does Transmural Permeability of the biomaterial in NGCs affect nerve repair?

Answer 18

• Solute exchange arises between nerve and surrounding fluid
• Semipermeable tubes are more successful than impermeable silcone elastomer or freely permeable e-PTFE
• More myelinated axons less connective tissue
• MW cut-off 50 000 to 100 000 is optimal
• PAN / PVC support good regeneration
• Oxygen levels
• Excitatory and growth factors stay in
• Inhibitory factors stay out

Question 19

How does Surface texture / Microgeometry of the biomaterial in NGCs affect nerve repair?

Answer 19

Microgeometry of luminal surface regulates tissue outgrowth
High surface roughness increases irregular fascicle formation
Smooth lumen surface directs discrete nerve cable formation

Question 20

How does the Electrical charge characteristics of the biomaterial in NGCs affect nerve repair?

Answer 20

Direct current stimulation influences nerve regeneration
Electret (dielectric polymers) can be used as NGC e.g. PTFE
Positively poled PTFE tubes contain larger nerve cables with more myelin than negatively poled tubes

Question 21

What is poly-3-hydroxybutyrate (PHB)?

Answer 21

Polymer fibres pressed into sheets with unidirectional orientation for contact guidance

• Natural storage product of bacteria
• Biocompatible, non antigenic
• Hydrolytic degradation and reabsorbed in 24 - 30 month
• Degraded to normal blood

Question 22

What are the present strategies for bioengineering peripheral nerve?

Answer 22

Involve a combination of
Nerve guidance conduits
Growth factors
Schwann cells

NGCs made from hydrolysable polymers give promising results
PLLA, PLGA, P3HB

Ongoing research combines the above approaches for
Increasing regeneration distance
Improving extent and effectiveness of reinnervation

Question 23

What are the roles of schwann cells?

Answer 23

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

Question 24

What does a bioengineering nerve conduit consist of?

Answer 24

1) alginate gel + schwann cells

2) polyhydroxybutyrate

Question 25

How does a bioengineered nerve conduit work?

Answer 25

1) Aligned hydrolysable fibres 2) Directed growth of Schwann glial cells 3) Encouraging proximal axon sprouting and directing accurate re-growth

Question 26

What is the process for culturing schwann cells in electrospun conduits?

Answer 26

!) 1200 electrospun fibres inserted into silicone tubes 2) Continuous flow device connected 3) Schwann cells remotely seeded 4) Static period to enable adhesion 5) Flow period started 6) Grown for 96 hours - Static period to enable adhesion of Schwann cells to PLLA microfibres - Cells introduced for 10 to 120 minutes Conduits disassembled and relative cell number measured