– Allograft tissue for bridging nerve

discontinuities• From donated human peripheral nerves• Decellularized and sterile• Provides clean and clear pathways for

axons to grow through

– Shown to be superior to Type I Collagen Tube (Whitlock et al 2009)

– Clinical Study from Mayo Clinic (Karabekmez et al 2009)

• Demonstrates re-incorporation of allograft

• Excellent recovery of 2PD in 5-30 mm deficits

(Karabekmez et al., Hand, 2009 )

© AxoGen 2009

© AxoGen 2009

Handles similar to autograftCleansed and sterile

3-D ECM structure maintained Size matching: Lengths up to 50mm & diameters up to 5mm

The Natural Connection

©AxoGen 2009

©AxoGen 2009

©AxoGen 2009

Nerve Autograft Conduit

Hours

Days

Weeks

Months

Years

Bridging the Gap:Different Mechanisms for Repair

Hours

Days

Months

Years

How Nerve Conduits Work:Mechanism for Repair

Fluid seeps into the void of the conduit.Fluid seeps into the void of the conduit.

An hourglass shaped fibrin cable forms.An hourglass shaped fibrin cable forms.

Cell migration and axonal regeneration occurs, restricted by the thinnest portion.

Cell migration and axonal regeneration occurs, restricted by the thinnest portion.

Often the resulting tissue is visibly thinner, containing a limited number of regenerated axons.

Often the resulting tissue is visibly thinner, containing a limited number of regenerated axons.

Increasing Gap Length

Length Limitations of Conduits:Mechanism for Repair

At short gap lengths, the fibrin cable is robust enough to allow regeneration.

At short gap lengths, the fibrin cable is robust enough to allow regeneration.

Thinning restricts the regenerative space at longer gaps.

Thinning restricts the regenerative space at longer gaps.

Decreasing Effi

cacy

The cable does not form when length limits are exceeded. This can result in no regeneration or a neuroma.

The cable does not form when length limits are exceeded. This can result in no regeneration or a neuroma.

Clinical Outcomes with Conduits:Landmark Studies

Type of Nerve Gap Length % Failure* Other Findings Clinical PublicationDigital Nerves(Sensory)

0-4mm5-7mm8-25mm

0%39%29%

34% failure rate in gaps 5mm or greater

Weber et al, 2000.

Digital Nerves(Sensory)

6-18mm 25% 100% of gaps greater than 16mm failed

Lohmeyer et al, 2009.

Digital Nerves(Sensory)

5-30mm 14% 27% reported poor resolution of pain

Mackinnon et al, 1990.

Sensory, mixed and motor nerves

2.5-20mm 57% 31% required revision Wangensteen et al, 2009.

* No or poor sensory recovery as defined by MRCC scale.* No or poor sensory recovery as defined by MRCC scale.

Avance® provides 3-D scaffolding to support the body’s own regeneration process.

Clean and clear pathways allow cell migration and axonal regeneration.

Axon regeneration is well-distributed throughout the cross-section.

Avance® is incorporated into the patient’s own tissue.

Hours

Days

Months

Years

How Avance® Works:Mechanism for Repair

Preclinical Comparative Study(Whitlock et al., Muscle Nerve, 2009)

Electrical Stimulation(28 mm, 22 Weeks)

Test Group Positive Responses

Conduit 0/9

Allograft(Avance®

process)7/9

Isograft 9/9

Isograft AxoGen® NeuraGen®

28mm, 22 weeks (midgraft). Scale bars = 20µm

Summary of Results: “AxoGen processed allografts are superior to a currently available conduit-style nerve guide,

the Integra NeuraGen®.”

•6 weeks, 14mm gapAllograft>20x Myelinated Fibers vs. Conduit

•22 weeks, 28mm gapAllograft>20x Myelinated Fibers vs. Conduit

Avance® Clinical Study(Karabekmez et al., Hand, 2009)

- 10 nerve injuries, gaps ranging from 0.5 to 3cm

- Sensory improvement in all patients

- Data at 9 months shows recovery in the excellent range• Moving 2PD: 4.4mm, Static 2PD: 5.5mm

- Graft shown to be re-incorporated into the repair site• 8 weeks post Avance® implant patient

returned for a revision of his Dupuytren’s contracture repair

• At ~20 wks moving 2PD was 7mm