J Korean Neurosurg Soc.  2013 Feb;53(2):65-71. 10.3340/jkns.2013.53.2.65.

Rat Peripheral Nerve Regeneration Using Nerve Guidance Channel by Porcine Small Intestinal Submucosa

Affiliations
  • 1Department of Neurosurgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea. yangjiho1963@gmail.com

Abstract


OBJECTIVE
In order to develop a novel nerve guidance channel using porcine small intestinal submucosa (SIS) for nerve regeneration, we investigated the possibility of SIS, a tissue consisting of acellular collagen material without cellular immunogenicity, and containing many kinds of growth factors, as a natural material with a new bioactive functionality.
METHODS
Left sciatic nerves were cut 5 mm in length, in 14 Sprague-Dawley rats. Grafts between the cut nerve ends were performed with a silicone tube (Silicon group, n=7) and rolled porcine SIS (SIS group, n=7). All rats underwent a motor function test and an electromyography (EMG) study on 4 and 10 weeks after grafting. After last EMG studies, the grafts, including proximal and distal nerve segments, were retrieved for histological analysis.
RESULTS
Foot ulcers, due to hypesthesia, were fewer in SIS group than in Silicon group. The run time tests for motor function study were 2.67 seconds in Silicon group and 5.92 seconds in SIS group. Rats in SIS group showed a better EMG response for distal motor latency and amplitude than in Silicon group. Histologically, all grafts contained some axons and myelination. However, the number of axons and the degree of myelination were significantly higher in SIS group than Silicon group.
CONCLUSION
These results show that the porcine SIS was an excellent option as a natural biomaterial for peripheral nerve regeneration since this material contains many kinds of nerve growth factors. Furthermore, it could be used as a biocompatible barrier covering neural tissue.

Keyword

Small intestinal submucosa; Sciatic nerve; Peripheral nerve regeneration; Myelination

MeSH Terms

Animals
Axons
Collagen
Electromyography
Foot Ulcer
Hypesthesia
Intercellular Signaling Peptides and Proteins
Myelin Sheath
Nerve Growth Factor
Nerve Growth Factors
Nerve Regeneration
Peripheral Nerves
Rats
Rats, Sprague-Dawley
Regeneration
Sciatic Nerve
Silicones
Transplants
Collagen
Intercellular Signaling Peptides and Proteins
Nerve Growth Factor
Nerve Growth Factors
Silicones

Figure

  • Fig. 1 The two photographs on the left are porcine small intestines and the photograph on the right is a prepared small intestinal submucosa.

  • Fig. 2 Upper two materials are a small and long silicone tube. Lower materials are small intestinal submucosa (SIS) sheet and a rolled steel rod SIS with 1.5 mm in diameter.

  • Fig. 3 Intra-operative photograph of the post-grafting procedure. The left sciatic nerve has been transected to create a 5 mm defect and a 7 mm small intestinal submucosa graft (black arrows) was placed into the nerve defect and sutured with 9-0 nylon.

  • Fig. 4 Photograph of run time apparatus to test motor function.

  • Fig. 5 A : Effects of small intestinal submucosa (SIS) extract and nerve growth factor (NGF) on PC-12 cells. The left column is the first day culture, the middle is the second and the right is the fourth. The first row is the control group, the second is the NGF group (NGF 10 ng/mL), the third is 5% SIS extract (5-SIS) and the fourth is 0.5% SIS extract (0.5-SIS). The neurites of PC-12 cells formed much more on the NGF and SIS extract containing medium than the control (×400 magnifications). B : Effects of SIS extract and NGF on PC-12 cells (*p<0.05 compared with control). The number and length of PC-12 cell neurites were in the order of 5% SIS extract>NGF>0.5% SIS extract>control.

  • Fig. 6 Photograph of foot ulcer due to sensory disturbance.

  • Fig. 7 A : Longitudinal section of nerves (Silicon group, ×200 magnifications). B : Longitudinal section of nerves [small intestinal submucosa (SIS) group, ×200 magnifications]. Multiple small cross striations of nerves are Ranvier's nodes of myelinated axons. The photograph on the left (Silicon group) shows about 10% of myelinated axons but the one on the right (SIS group) shows nearly 100% of myelinated axons. C : Cross section of silicon implanted nerve (Silicon group, ×40 magnifications). D : Cross section of SIS implanted nerve (SIS group, ×40 magnifications). SIS group (right photograph) shows more cells and vessels than Silicon group (left photograph, Silicon group). Hematoxylin and eosin staining.

  • Fig. 8 Electron microscope picture of the distal part of the graft in the small intestinal submucosa group; note the thick myelin (black arrow).


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