Nerve Allografts:State of the Art

Nickolaos A. Darlis, MD, PhD

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NERVE AUTOGRAFTING

Gold Standard in setting of a nerve gap“ Expendable” donors: • Sensory: – MABC – LABC – Sural

Non immunogenic ‐• Sensory donors do not support motor regeneration as

well as mixed sensorimotor or pure motor nerves

• Motor: -AIN -PIN -Nerve to gracilis

NERVE AUTOGRAFTINGthe “down side”

• Harvest site morbidity (scarring, neuroma formation, loss of donor function) (20-30% with painful donor site, cold

sensitivity, function alteration )• Harvest time/cost• Limited size and length available

Long Nerve grafts• Long nerve grafts highly

successful in only one series (biceps)• Prognosis is nerve and site-

specific • Axillary nerve graft results

mixed, generally 50% effective • Reduced time to surgery,

shorter grafts associated with improved outcomes

Vascularized nerve grafts

• Vascular pedicled ulnar nerve graft may offer some advantages in poorly vascularized bed, but no definitive data to support routine use

CONDUITS

• Often used for <3cm gaps in small-diameter sensory nerves

• Potentially longer with biologic supplementation • More questions about large mixed nerves– Mackinnon, 2014 :In my practice, nerve conduits have

largely been replaced by acellularized nerve allografts

CONDUITSthe “down side”

• Use limited to small gaps;– 34%-57% failure rate >5mm gaps

• cost• lack laminin scaffolding • lack Schwann Cells, which are crucial to axonal

regeneration • Semi-rigid material cannot be used around joints

CONDUITSthe “down side”

• decreased concentration of neurotrophic factors associated with larger diameter conduits

CONDUITSthe “down side”

• isograft is superior to nerve conduit even with minced nerve • no significant difference in regeneration among motor,

sensory, or mixed minced nerves

NERVE TRANSFERS

NERVE ALLOGRAFTS

• taken from ABO blood type compatible individuals‐– cadaveric – living related donor

• small diameter nerves (avoid necrosis of central aspect of nerve from lack of adequate

revascularization)

NERVE ALLOGRAFTS• NERVE ALLOTRANSPLANTATION PATIENT PROTOCOL:

NERVE ALLOGRAFTS• Schwann Cell Migration

• Axonal Growth• Longitudinal revascularization

NERVE ALLOGRAFTS

• Mackinnon, 2014 :”should be reserved for unique patients with irreparable peripheral nerve injuries, which, left untreated, would lead to an essentially nonfunctional limb”

ACELLULARIZED NERVE GRAFT • Harvested from cadavers (Motor

nerves ,no branching)• Decellularized with detergents

(Hudson et al.) • Subjected to enzymatic degradation

of CSPGs with chondroitinase (Neubauer et al.)

• Grafts sterilized with gamma irradiation

• Stored at 80 C ‐

Preserved Architecture

ACELLULARIZED NERVE GRAFT• Schwann Cell Migration

• Axonal Growth• Longitudinal revascularization

ACELLULARIZED NERVE GRAFT

• , ,USA

• Guangzhou Zhongda Medical Devices Company, Chinaloaded with:

– brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells

– platelet-rich plasma– Ginkgo biloba extract

ACELLULARIZED NERVE GRAFTanimal study

• Isograft > Acellularized Nerve Graft> Conduit

ACELLULARIZED NERVE GRAFTclinical studies

• RANGER® Study (ongoing)• Meaningful Recovery (S3-S4 and M3-M5) in 87% of nerve

reconstructions

• No graft-related complications

ACELLULARIZED NERVE GRAFTclinical studies

• MATCH® control arm of RANGER® study (ongoing)• Outcomes are comparable to nerve autograft and

exceed those for nerve conduit in historical controls.

ACELLULARIZED NERVE GRAFTskepticism

• McKinnon, 2014: “ contraindicated in motor nerve & critical sensory nerve reconstruction ; autologous repair with autograft or nerve transfer would always be my reconstruction of choice in these defects”

• 2013 ASSH, San Francisco, CA: straw poll taken during allograft nerve session found that the overwhelming majority of surgeons would prefer autograft to processed allograft if it were their own mixed nerve being repaired.

N. Tibial

N. Common Peroneal

N. Sciatic

• Pros– Safe (as per studies)– Single graft repair, no need for multiple cable graft orientation– Multiple length and diameters (only up to 7cm length)– Excellent handling properties– Supporting clinical studies (ongoing)– Time efficient– ? Revision

• Cons– Cost– Must have a prediction of nerve and gap size– Logistics ( scheduling, transfer and storage)– Compromised host?/ previous infection?/ scarred bed?

Thank you

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