Can a Small Intestine Segment Be an Alternative Biological Conduit for Peripheral Nerve Regeneration?

Abstract

Background: Autologous nerve grafts are used to bridge peripheral nerve defects. Limited sources and donor site morbidity are the major problems with peripheral nerve grafts. Although various types of autologous grafts such as arteries, veins and muscles have been recommended, an ideal conduit has not yet been described. Aims: To investigate the effectiveness of a small intestinal conduit for peripheral nerve defects. Study Design: Animal experimentation. Methods: Twenty-one rats were divided into three groups (n=7). Following anaesthesia, sciatic nerve exploration was performed in the Sham group. The 10 mm nerve gap was bridged with a 15 mm ileal segment in the small intestinal conduit group and the defect was replaced with orthotopic nerve in autologous nerve graft group. The functional recovery was tested monthly by walking-track analysis and the sciatic functional index. Histological evaluation was performed on the 12th week. Results: Sciatic functional index tests are better in autologous nerve graft group (-55.09±6.35); however, during follow-up, progress in sciatic functional index was demonstrated, along with axonal regeneration and innervation of target muscles in the small intestinal conduit group (-76.36±12.08) (p<0.05). In histologic sections, distinctive sciatic nerve regeneration was examined in the small intestinal conduit group. The expression of S-100 and neurofilament was observed in small intestinal conduit group but was less organised than in the autologous nerve graft group. Although the counted number (7459.79±1833.50 vs. 4226.51±1063.06 mm2), measured diameter [2.19 (2.15-2.88) vs. 1.74 (1.50-2.09) µm] and myelin sheath thickness [1.18 (1.09-1.44) vs. 0.66 (0.40-1.07) µm] of axons is significantly high in the middle sections of autologous nerve graft compared to the small intestinal conduit group, respectively (p<0.05), the peripheral nerve regeneration was also observed in the small intestinal conduit group. Conclusion: Small intestinal conduit should not be considered as an alternative to autologous nerve grafts in its current form; however, the results are promising. Even though the results are no better than autologous nerve grafts, with additional procedures, it might be a good alternative due to harvesting abundant sources without donor site morbidity.

Keywords

• Peripheral nerve injury, small intestine, conduits

References

1. 1. Sinis N, Kraus A, Drakotos D, Doser M, Schlosshauer B, Muller HW, et al. Bioartificial reconstruction of peripheral nerves using the rat median nerve model. Ann Anat 2011;193:341-6.
2. 2. Bellamkonda RV. Peripheral nerve regeneration: an opinion on channels, scaffolds and anisotropy. Biomaterials 2006;27:3515-8.
3. 3. Battiston B, Geuna S, Ferrero M, Tos P. Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair. Microsurgery 2005;25:258-67.
4. 4. Siemionow M, Demir Y, Mukherjee AL. Repair of peripheral nerve defects with epineural sheath grafts. Ann Plast Surg 2010;65:546-54.
5. 5. Muheremu A, Ao Q. Past, Present, and Future of Nerve Conduits in the Treatment of Peripheral Nerve Injury. Biomed Res Int 2015;2015:237507.
6. 6. Sabongi RG, Fernandes M, Dos Santos JB. Peripheral nerve regeneration with conduits: use of vein tubes. Neural Regen Res 2015;10:529-33.
7. 7. Yang XN, Jin YQ, Bi H, Wei W, Cheng J, Liu ZY, et al. Peripheral nerve repair with epimysium conduit. Biomaterials 2013;34:5606-16.
8. 8. Tos P, Battiston B, Geuna S, Giacobini-Robecchi MG, Hill MA, Lanzetta M, et al. Tissue specificity in rat peripheral nerve regeneration through combined skeletal muscle and vein conduit grafts. Microsurgery 2000;20:65-71.

9. 9. Neto HS, Pertille A, Teodori RM, Somazz MC, Marques MJ. Primary nerve repair by muscle autografts prepared with local anesthetic. Microsurgery 2004;24:188-93.
10. 10. Palhares A, Viterbo F, Cardoso RG. Muscle graft as a substitute for peripheral nerve graft in rats. Acta Cir Bras 2009;24:221-5.
11. 11. Rao P, Kotwal PP, Farooque M, Dinda AK. Muscle autografts in nerve gaps. Pattern of regeneration and myelination in various lengths of graft: an experimental study in guinea pigs. J Orthop Sci 2001;6:527-34.
12. 12. Ayhan S, Yavuzer R, Latifoglu O, Atabay K. Use of the turnover epineurial sheath tube for repair of peripheral nerve gaps. J Reconstr Microsurg 2000;16:371-8.
13. 13. Brunelli GA, Battiston B, Vigasio A, Brunelli G, Marocolo D. Bridging nerve defects with combined skeletal muscle and vein conduits. Microsurgery 1993;14:247-51.
14. 14. Hadlock TA, Sundback CA, Hunter DA, Vacanti JP, Cheney ML. A new artificial nerve graft containing rolled Schwann cell monolayers. Microsurgery 2001;21:96-101.
15. 15. Smith RM, Wiedl C, Chubb P, Greene CH. Role of small intestine submucosa (SIS) as a nerve conduit: preliminary report. J Invest Surg 2004;17:339-44.
16. 16. Yi JS, Lee HJ, Lee HJ, Lee IW, Yang JH. Rat peripheral nerve regeneration using nerve guidance channel by porcine small intestinal submucosa. J Korean Neurosurg Soc 2013;53:65-71.
17. 17. Geuna S, Tos P, Titolo P, Ciclamini D, Beningo T, Battiston B. Update on nerve repair by biological tubulization. J Brachial Plex Peripher Nerve Inj 2014;9:3.
18. 18. Manoli T, Schulz L, Stahl S, Jaminet P, Schaller HE. Evaluation of sensory recovery after reconstruction of digital nerves of the hand using musclein-vein conduits in comparison to nerve suture or nerve autografting. Microsurgery 2014;34:608-15.
19. 19. Mohammadi R, Azizi S, Delirezh N, Hobbenaghi R, Amini K. Comparison of beneficial effects of undifferentiated cultured bone marrow stromal cells and omental adipose-derived nucleated cell fractions on sciatic nerve regeneration. Muscle Nerve 2011;43:157-63.
20. 20. Mohammadi R, Azizi S, Delirezh N, Hobbenaghi R, Amini K, Malekkhetabi P. The use of undifferentiated bone marrow stromal cells for sciatic nerve regeneration in rats. Int J Oral Maxillofac Surg 2012;41:650-6.
21. 21. Sahin C, Karagoz H, Kulahci Y, Sever C, Akakin D, Kolbasi B, et al. Minced nerve tissue in vein grafts used as conduits in rat tibial nerves. Ann Plast Surg 2014;73:540-6.
22. 22. Wang X, Luo E, Li Y, Hu J. Schwann-like mesenchymal stem cells within vein graft facilitate facial nerve regeneration and remyelination. Brain Res 2011;1383:71-80.
23. 23. Haghighat A, Mohammadi R, Amini K. Transplantation of undifferentiated bone-marrow stromal cells into a vein graft accelerates sciatic nerve regeneration in streptozotocin induced diabetic rats. Curr Neurovasc Res 2014;11:230-41.
24. 24. Papalia I, Raimondo S, Ronchi G, Magaudda L, Giacobini-Robecchi MG, Geuna S. Repairing nerve gaps by vein conduits filled with lipoaspirate-derived entire adipose tissue hinders nerve regeneration. Ann Anat 2013;195:225-30.
25. 25. Su Y, Zeng BF, Zhang CQ, Zhang KG, Xie XT. Study of biocompatibility of small intestinal submucosa (SIS) with Schwann cells in vitro. Brain Res 2007;1145:41-7.
26. 26. Luo JC, Chen W, Chen XH, Qin TW, Huang YC, Xie HQ, et al. A multistep method for preparation of porcine small intestinal submucosa (SIS). Biomaterials 2011;32:706-13.
27. 27. Zheng MH, Chen J, Kirilak Y, Willers C, Xu J, Wood D. Porcine small intestine submucosa (SIS) is not an acellular collagenous matrix and contains porcine DNA: possible implications in human implantation. J Biomed Mater Res B Appl Biomater 2005;73:61-7.
28. 28. Hong S, Kim G. Electrospun micro/nanofibrous conduits composed of poly (epsilon-caprolactone) and small intestine submucosa powder for nerve tissue regeneration. J Biomed Mater Res B Appl Biomater 2010;94:421-8.
29. 29. Pabari A, Lloyd-Hughes H, Seifalian AM, Mosahebi A. Nerve conduits for peripheral nerve surgery. Plast Reconstr Surg 2014;133:1420-30.