1. – 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

2. Handles similar to autograft Cleansed and sterile 3-D ECM structure maintained Size matching: Lengths up to 50mm & diameters up to 5mm The Natural Connection ©AxoGen 2009

3. Nerve AutograftConduit Hours Days Weeks Months Years Bridging the Gap: Different Mechanisms for Repair

4. Hours Days Months Years How Nerve Conduits Work: Mechanism for Repair Fluid seeps into the void of the conduit. An hourglass shaped fibrin cable forms. 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.

5. Increasing Gap Length Length Limitations of Conduits: Mechanism for Repair At short gap lengths, the fibrin cable is robust enough to allow regeneration. Thinning restricts the regenerative space at longer gaps. Decreasing Efficacy The cable does not form when length limits are exceeded. This can result in no regeneration or a neuroma.

6. Clinical Outcomes with Conduits: Landmark Studies Type of NerveGap Length% Failure*Other FindingsClinical Publication Digital Nerves (Sensory) 0-4mm 5-7mm 8-25mm 0% 39% 29% 34% failure rate in gaps 5mm or greater Weber et al, 2000. Digital Nerves (Sensory) 6-18mm25%100% of gaps greater than 16mm failed Lohmeyer et al, 2009. Digital Nerves (Sensory) 5-30mm14%27% reported poor resolution of pain Mackinnon et al, 1990. Sensory, mixed and motor nerves 2.5-20mm57%31% required revisionWangensteen et al, 2009. * No or poor sensory recovery as defined by MRCC scale.

7. 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

8. Preclinical Comparative Study (Whitlock et al., Muscle Nerve, 2009 ) Electrical Stimulation (28 mm, 22 Weeks) Test Group Positive Responses Conduit0/9 Allograft (Avance ® process) 7/9 Isograft9/9 IsograftAxoGen ® 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 gap Allograft>20x Myelinated Fibers vs. Conduit 22 weeks, 28mm gap Allograft>20x Myelinated Fibers vs. Conduit

9. 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