J Reconstr Microsurg 2011; 27(2): 083-090
DOI: 10.1055/s-0030-1267834
© Thieme Medical Publishers

Nerve Endoneurial Microstructure Facilitates Uniform Distribution of Regenerative Fibers: A Post Hoc Comparison of Midgraft Nerve Fiber Densities

Philip J. Johnson1 , Piyaraj Newton1 , Daniel A. Hunter1 , Susan E. Mackinnon1
  • 1Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, Missouri
Further Information

Publication History

Publication Date:
13 October 2010 (online)

ABSTRACT

Despite their inferiority to nerve autograft, clinical alternatives are commonly used for reconstruction of peripheral nerve injuries because of their convenient off-the-shelf availability. Previously, our group compared isografts with NeuraGen® (Integra, Plainsboro, NJ) nerve guides, which are a commercially available type I collagen conduit and processed rat allografts comparable to Avance® (AxoGen, Alachua, FL) human decellularized allograft product. From this study, qualitative observations were made of distinct differences in the pattern of regenerating fibers within conduits, acellular allografts, and isografts. In the current post hoc analysis, these observations were quantified. Using nerve density, we statistically compared the differential pattern of regenerating axon fibers within grafts and conduit. The conduits exhibited a consistent decrease in midgraft density when compared with the isograft and acellularized allografts at two gap lengths (14 mm and 28 mm) and time points (12 and 22 weeks). The decrease in density was accompanied by clustered distribution of nerve fibers in conduits, which contrasted the evenly distributed regeneration seen in processed allografts and isografts. We hypothesize that the lack of endoneurial microstructure of conduits results in the clustering regenerating fibers, and that the presence of microstructure in the acellularized allograft and isografts facilitates even distribution of regenerating fibers.

REFERENCES

  • 1 Moore A M, Kasukurthi R, Magill C K, Farhadi H F, Borschel G H, Mackinnon S E. Limitations of conduits in peripheral nerve repairs.  Hand (N Y). 2009;  4 180-186
  • 2 Whitlock E L, Tuffaha S H, Luciano J P et al.. Processed allografts and type I collagen conduits for repair of peripheral nerve gaps.  Muscle Nerve. 2009;  39 787-799
  • 3 Meek M F, Coert J H. Clinical use of nerve conduits in peripheral-nerve repair: review of the literature.  J Reconstr Microsurg. 2002;  18 97-109
  • 4 Meek M F, Coert J H. US Food and Drug Administration/Conformit Europe-approved absorbable nerve conduits for clinical repair of peripheral and cranial nerves.  Ann Plast Surg. 2008;  60 466-472
  • 5 Karabekmez F E, Duymaz A, Moran S L. Early clinical outcomes with the use of decellularized nerve allograft for repair of sensory defects within the hand.  Hand (N Y). 2009;  4 245-249
  • 6 Williams L R, Longo F M, Powell H C, Lundborg G, Varon S. Spatial-temporal progress of peripheral nerve regeneration within a silicone chamber: parameters for a bioassay.  J Comp Neurol. 1983;  218 460-470
  • 7 Hudson A R, Morris J, Weddell G, Drury A. Peripheral nerve autografts.  J Surg Res. 1972;  12 267-274
  • 8 Hudson T W, Liu S Y, Schmidt C E. Engineering an improved acellular nerve graft via optimized chemical processing.  Tissue Eng. 2004;  10 1346-1358
  • 9 Johnson P C, Duhamel R C, Meezan E, Brendel K. Preparation of cell-free extracellular matrix from human peripheral nerve.  Muscle Nerve. 1982;  5 335-344
  • 10 Sondell M, Lundborg G, Kanje M. Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction.  Brain Res. 1998;  795 44-54
  • 11 Atchabahian A, Mackinnon S E, Hunter D A. Cold preservation of nerve grafts decreases expression of ICAM-1 and class II MHC antigens.  J Reconstr Microsurg. 1999;  15 307-311
  • 12 Evans P J, Mackinnon S E, Best T J et al.. Regeneration across preserved peripheral nerve grafts.  Muscle Nerve. 1995;  18 1128-1138
  • 13 Evans P J, Mackinnon S E, Levi A D et al.. Cold preserved nerve allografts: changes in basement membrane, viability, immunogenicity, and regeneration.  Muscle Nerve. 1998;  21 1507-1522
  • 14 Evans P J, MacKinnon S E, Midha R et al.. Regeneration across cold preserved peripheral nerve allografts.  Microsurgery. 1999;  19 115-127
  • 15 Fox I K, Jaramillo A, Hunter D A, Rickman S R, Mohanakumar T, Mackinnon S E. Prolonged cold-preservation of nerve allografts.  Muscle Nerve. 2005;  31 59-69
  • 16 Hess J R, Brenner M J, Fox I K et al.. Use of cold-preserved allografts seeded with autologous Schwann cells in the treatment of a long-gap peripheral nerve injury.  Plast Reconstr Surg. 2007;  119 246-259
  • 17 Zalewski A A, Silvers W K. An evaluation of nerve repair with nerve allografts in normal and immunologically tolerant rats.  J Neurosurg. 1980;  52 557-563
  • 18 Hudson T W, Zawko S, Deister C et al.. Optimized acellular nerve graft is immunologically tolerated and supports regeneration.  Tissue Eng. 2004;  10 1641-1651
  • 19 Neubauer D, Graham J B, Muir D. Chondroitinase treatment increases the effective length of acellular nerve grafts.  Exp Neurol. 2007;  207 163-170
  • 20 Carr M M, Best T J, Mackinnon S E, Evans P J. Strain differences in autotomy in rats undergoing sciatic nerve transection or repair.  Ann Plast Surg. 1992;  28 538-544
  • 21 Hunter D A, Moradzadeh A, Whitlock E L et al.. Binary imaging analysis for comprehensive quantitative histomorphometry of peripheral nerve.  J Neurosci Methods. 2007;  166 116-124
  • 22 Evans P J, Bain J R, Mackinnon S E, Makino A P, Hunter D A. Selective reinnervation: a comparison of recovery following microsuture and conduit nerve repair.  Brain Res. 1991;  559 315-321
  • 23 Francel P C, Francel T J, Mackinnon S E, Hertl C. Enhancing nerve regeneration across a silicone tube conduit by using interposed short-segment nerve grafts.  J Neurosurg. 1997;  87 887-892
  • 24 Lee A C, Yu V M, Lowe III J B et al.. Controlled release of nerve growth factor enhances sciatic nerve regeneration.  Exp Neurol. 2003;  184 295-303
  • 25 Mackinnon S E, Dellon A L. A study of nerve regeneration across synthetic (Maxon) and biologic (collagen) nerve conduits for nerve gaps up to 5 cm in the primate.  J Reconstr Microsurg. 1990;  6 117-121
  • 26 Maeda T, Mackinnon S E, Best T J, Evans P J, Hunter D A, Midha R T. Regeneration across “stepping-stone” nerve grafts.  Brain Res. 1993;  618 196-202
  • 27 Wood M D, Moore A M, Hunter D A et al.. Affinity-based release of glial-derived neurotrophic factor from fibrin matrices enhances sciatic nerve regeneration.  Acta Biomater. 2009;  5 959-968
  • 28 Belkas J S, Shoichet M S, Midha R. Peripheral nerve regeneration through guidance tubes.  Neurol Res. 2004;  26 151-160
  • 29 Panseri S, Cunha C, Lowery J et al.. Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections.  BMC Biotechnol. 2008;  8 39

Philip J JohnsonPh.D. 

Assistant Professor, Department of Surgery, Division of Plastic and Reconstructive Surgery

660 South Euclid, Box 8238, Saint Louis, MO 63110

Email: johnsonp@wudosis.wustl.edu