1. Luis Landin, MD, PhD Plastic & Reconstructive Surgery University Hospital “La Paz” Madrid, Spain What are the alternatives to nerve grafts ? Conduits, allografts, vascularized grafts, vascularized allografts

2. Different options to reconstruct nerve different defects Introduction Ducic; Ann Plast Surg 2012 Tension-free timely repair

3. Indications Ducic; Ann Plast Surg 2012

4. Mackinnon, Exp Neurol 2010 Autografts 4 cm autograft usually required after failed primary repair. Sural, peroneal, anterior MABC End-to-side donor to adjacent may minimize morbidity Indications Nerve transfers Proximity Expendable Synergism Matching Preclude tendon transfers of donors

5. Mackinnon, Exp Neurol 2010 End-to-side Proximal stump not available Controversial results (Bertelli). Donor nerve axotomy for motor axon sprouting (not sensory) Indications Nerve allografts Very large defects Provide Schwann cells (P vs. C) Naïve allografts require temporary IS Decellularized allografts

6. Complicated by several factors: Mechanism of injury. Time of presentation. Soft-tissue or bone damage. Patient conditions. Techniques: sutures, glues, connectors. Mobility of nerve location Further complicated by difficulty to measure the outcomes (CBOs vs. PROs) Comparisons

7. Non-porous silicone chambers: limited results PGA (Neurotube) Weber, PRS 2000 First randomized, multicenter, blinded study 98 subjects, 136 digital nerves Neurotube vs. autografts Non-significant differences as a whole Limitation: 25% lost to follow-up Nerve conduits Gap >8-mm

8. Collagen conduits (NeuraGen) Taras, JHS A 2011 Prospective study w/o control 19 patients, 22 digital nerves Type I bovine collagen tube Gaps < 2 cm All patients recovered S3 No pain E +G 16/22 F 6/22 Nerve conduits

9. Caprolactone conduits (Neurolac) Bertleff, JHS A 2005 Randomized prospective multicenter study 30 patients 21 conduits, PR or NG Gaps < 2 cm Differences were not significant Nerve conduits

10. Deal, J AAOS 2012 Caprolactone >> Collagen>> PGA Nerve conduits

11. Naïve Decellularized (AxoGen) Nerve allografts

12. Mackinnon, PRS 2000 Any length Endless supply Short-term IS needed IS allegedly enhances neural recovery Naïve nerve allografts Halloran PF. N Engl J Med 2004 Nerve allografts are avascular Rejected within 9 days after tx Favored by antigen presentation by potent class II cells: donor Schwann cells Basal laminae tubes Schwann cells are destroyed No axonal guidance Vascularized nerve allografts Under IS are similar to VN isografts in rats. Need for IS (Best, PRS 1992; Doi, APS 1994)

13. Atchabahian, Restor Neurol Neurosci 1998 Allografts under IS are biologic conduits Work even after rejection May become a reversed chimera Are rejected by the donor Nerve allografts Mackinnon, PRS 1992 First clinical transplant Gap range: 12 – 37 cm Mean graft length: 190 cm. 6/7 survived Defended the use of tacrolimus

14. Whitlock, Muscl Nerv 2009 Non-significant differences Autograft vs. allograft vs. conduit

15. Guisti, JBJS Am 2012 Significant differences Autograft vs. allograft vs. conduit

16. Adequate intraneural perfusion Not possible to pre-fabricate in rats Kanaya; PRS 1992 Vascularized nerve grafts

17. Experimental daily, systemic administration of low-dose FK506 facilitates peripheral nerve recovery and regeneration after nerve grafting in rats. Axonal regeneration enhancers Doolabh, PRS 1999 Bioabsorbable tubes enhanced with stem-cell derived neurospheres Uemura, BBRC 2012 Chondroitinase after CTA Tuffaha, JHS A 2011

18. Ducic, Ann Plast Surg 2012 Retrospective review 47 patients Neuragen, Neurotube, AxoGen Differences were not significant. Limitations: Location of injury PR vs. autograft vs. conduit vs. allograft

19. Hand transplants Moore, Hand 2009

20. Hand transplants

22. Schuind, JHS E 2012 Worked on the hypothesis that hand tx work well because of tacrolimus (Tinel sign advancing 3 mm/day) Background:experimental research clinical experience nerve transplants clinical experience arm replant Phase II open prospective study Aim: evaluate speed and quality of regeneration of 2 months of oral FK506 medication at transplantation dosages after nerve repair. Major nerve arm, forearm, leg; PR or NG; 5-8 ng/mL 4/6 patients finished the study Speed: 1.5 mm/day (not significant); none DS<10 mm; none full motor recovery IS there a clinical significance? Clinical use of enhancer tacrolimus

23. Many reconstructive options Many types of injury Difficult evaluation, not always validated Primary repair and autografts remain the gold standard Complex injuries require thorough surgical plan to combine grafts and transfers Axonal regeneration enhancers Summary