Lecture by Dr Sreedharan TTSH Singapore

1. Overcoming Nerve Gap
(Review of allografts / conduits / wraps in nerve
reconstruction)
Sreedharan Sechachalam
Hand and Microsurgery Section
Tan Tock Seng Hospital
Singapore

2. Factors determining prognosis
following nerve injury
• Nature of injury
• Age
• Level of injury
• Type of nerve
• Nerve gap
• Condition of nerve ends
• Delay between injury and repair

3. Nerve Repair / Reconstruction
• Aim
– Direct the regenerating nerve fibres into the
appropriate distal endoneurial tube with
minimal loss of nerve fibres at the injury site

4. Principles of Nerve Repair
• Under magnification
• Careful dissection & mobilisation
• Adequate debridement
• Correct orientation
• Tension free
• Skeletal stability, healthy bed

5. For all nerve transections:
•Nerve stumps adequately
debrided
•‘Fascicular bloom’
•Punctate bleeding at cut ends
•Associated joint ranged
•Then, is there nerve gap?
Safa B et al. Autograft substitutes.
Hand Clin 2016

6. How to overcome
nerve gap
• Early repair
• Mobilisation
– Excessive mobilisation > ischemia
• Transposition
• Bone shortening
• Grafts & Conduits

7. Nerve Reconstruction
• Principle: To bridge the nerve gap &
alleviate tension at coaptation site
• Autografts
• Conduits
• Allografts

8. Autograft: Gold standard

9. Donor Nerves
Neligan – Plastic Surgery
Sebastin & Chung – Operative techniques in hand surgery, 2nd
ed
**SRN – only used when there is a irrepairable prox nerve injury e.g.
BPI
- no expectation of functional recovery of sensation

10. Terminal branch of PIN
• Floor of 4th
extensor
compartment
• 5 cm (1-3 fascicles)
• Ideal size for digital
nerve defects
• No loss of function

11. Autografts
• Advantages
– Biocompatible scaffold
– Growth factors & adhesion molecules
• Cons
– Donor site morbidity (Surgical incision,
sensory loss)
– Limited source
– Mismatch

12. Conduits
• 1880s – Themistocles Gluck,
Gustave Neuber
• decalcified bone tubes for nerve reconstruction to
allow the nerve to climb “…up the scaffold of the
implanted foreign body as vine climbing a staff”
• 1909 – Wrede – saphenous vein
• 1982 – Chiu – autogenous nerve
conduit
• 1990 – Mackinnon & Delon - PGA
iJpma et al (2008) The early history of tubulation in nerve repair
Strauch (2013) Nerve conduits: an update on tubular nerve repair & reconstruction. JHS;38A:1252-55

13. Nerve Conduits
• Avoid donor site morbidity
• Creates isolated environment
surrounding repair site
• Contain cytokines
• Protection from fibroblasts &
inflammatory cells
• Prevent mechanical obstruction
• Guides sprouting axons
Rivlin et al (2010) The role of nerve allografts and conduits for nerve injuries. Hand Clin;26:435-446

14. Conduits
• Mode of action
– Encases distal and proximal ends within tube
and provides gross macroalignment for the
nerve
– Containment of fluid leaking from the nerve
ends, gathering it within the chamber

15. (A)Protein-rich fluid
(neurotrophic factors)
(B)Fibrin-rich scaffold
(C)Cell migration
(perineurial, endothelial,
Schwann cells)
(D)Axonal cable
elongates
Kehoe et al (2012) FDA approved guidance conduits & wraps for peripheral nerve injury: A review of materials and efficacy.
Injury, Int J Care Injured;43:553-72

16. Ideal conduit
Characteristics
•Biocompatible
•No inflammatory response
•Biodegradable
•Flexible, soft
•Guidance cue for extending
growth cone
•Semi-permeable
•Retain secreted neurotrophic
factors
•Prevent fibrous tissue
ingrowth into injury site

17. Ideal conduit
Characteristics
•Biocompatible
•No inflammatory response
•Biodegradable
•Flexible, soft
•Guidance cue for extending
growth cone
•Semi-permeable
•Retain secreted neurotrophic
factors
•Prevent fibrous tissue
ingrowth into injury site

18. Conduit materials
• Silicone (nonpermeable, permanent)
– Soft tissue irritation, fibrotic encapsulation,
compression
• Modern biomaterials (permeable,
biodegradable)
– Denatured collagen, polyesters
– Permeable: diffusion of oxygen and
micronutrients
– First commercially available: Polyglycolic acid

19. Modern biomaterial conduits
• Polyglycolic acid (PGA) (Neuratube®)
– Rigid, thermoplastic polymer
– High rate of degradation, acidic
• Caprolactone (Neurolac®)
– Degrades more slowly than PGA
– Less acidic degradation products
– Clear
• Collagen (NeuraGen®)
– semi-permeable Type 1

20. Evidence is confusing ...
• PGA vs vein conduits – equivalent sensory recovery1
• Caprolactone vs primary repair – equivalent sensory
recovery2
• PGA - improved sensory recovery compared to primary
repair & autologous nerve graft (gaps ≤4mm or ≥8mm)3
• Collagen conduit vs autograft – comparable results, PGA
conduits poorer4
• Caprolactone tubes – only 1/12 major nerve repair
achieved good outcome5
1 Rinker & Liau (2011) Propsective randomized study comparing woven PGA & autogenous vein conduits for reconstruction
of digital nerve gaps. J Hand Surg Am;36(5):775-81
2 Bertleff (2005) A prospective clinical evaluation of biodegradable neurolac nerve guides for sensory nerve repair in the
hand. J Hand Surg Am;30(3):513-8
3 Weber et al (2000) A randomized prospective study of PGA conduits for digital nerve reconstruction in humans. Plast
Reconstr Surg;106(5):1036-45
4 Waitayawinyu et al (2007) A comparison of PGA vs type 1 collagen bioabsorbable nerve conduits in a rat model: an
alternative to autografting. J Hand Surg Am;32(10):1521-9
5 Chiriac et al (2012) Experience of using the bioresorbable copolyester nerve conduit Neurolac for nerve repair in peripheral
nerve defects. J Hand Surg Eur;37(4):342-9

21. Summary of evidence:
Synthetic conduits
• Most studies are with digital nerves
– < 10mm, good results --- recommendation
– > 30mm, bad results
• Major peripheral nerves
– Paucity of nonsponsored studies
– Mixed results
Safa B et al. Autograft substitutes.
Hand Clin 2016

22. Vein conduit
NRR 2015

23. Vein conduits
• Superficial veins, gaps<3cm
• Equivalent results to nerve autograft1,2
• Equivalent results to PGA, fewer
complications3
1 Calcagnotto & Silva (2006) The treatment of digital nerve defects by the technique of vein conduit with nerve segment. A
randomised prospective study. Chir Main;25(34):126-30
2 Chiu & Strauch (1990) A prospective clinical evaluation of autogenous vein grafts used as a nerve conduit for distal sensory
nerve defects of 3cm or less. Plast Reconstr Surg;86:928-34
3 Rinker & Liau (2011) Prospective randomized study comparing woven PGA & autogenous vein conduits for reconstruction
of digital nerve gaps. J Hand Surg Am;36(5):775-81

24. Nerve Allograft
• Allograft from cadaver donors
• Attractive option
– Benefits of conduits (size match, no donor
deficit, large supply)
– Ideal microenvironment for nerve healing
(microarchitecture, neurotrophic factors,
guidance cues)
• Disadvantages:
– Cost
– Immunosuppressive treatment
• Technique as for autograft

25. Nerve allograft:
Addressing the disadvantages
• Tissue engineering
– Extracts MHCs, myelin, cellular debris
• >>> reduces immunogenecity and need for
immunosuppression
• Unfortunately, these limits the regenerative
capacity as well
• Cost
– ? Exchanging cost of operating theatre for
cost of product (with all the other benefits)

28. Summary of results: Allografts
• Digital nerves
– Up to 30mm gap: Good results (at least 6mm
2PD)
– Up to 70mm gap: Meaningful recovery
• Major peripheral nerves
– Promising
– Up to 100mm gap
Safa B et al. Autograft substitutes.
Hand Clin 2016

29. Nerve wraps
• Following nerve
repairs / neurolysis
• Protect the repair
site from adhesion
formation
• Vein / Synthetic
• Synthetic: Selective
permeability allowing
nutrient diffusion
while blocking
fibroblast migration
Orthopaedics 2017

30. Safa B et al. Autograft substitutes.
Hand Clin 2016

31. Summary
•Transected nerve
– Debridement of ends
– Judiciously attempt to overcome nerve gap
– If necessary, nerve reconstruction
– Options: Autograft, conduit, allograft