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..

Figure 1. Harvesting a small intestine segment (a). Bridging the sciatic nerve gap with intestinal conduit and entabulating the proximal and distal stumps (b).

Figure 2. The sciatic functioning index measurement results of groups during follow up throughout 12th week, *indicates a significant difference between autologous nerve graft and small intestinal conduit (p<0.05). SFI: sciatic functioning index; ANG: autologous nerve graft; SIC: small intestinal conduit; W: week

Figure 3. Macroscopic appearance of regenerated small intestinal conduit constructs at 12 weeks.

Figure 4. Toluidine-blue stained sections of the small intestinal conduit complex from intraconduit (a, c) and distal stump (b, d). Note the regenerated neural elements within the fibrotic tissue throughout the intestinal segment, wallerian degeneration and weak axonal regeneration in the distal stump. Magnifcations at 10X [above (a, b), Scale bar=100 μm] and 40X [below (c, d), Scale bar=50 μm]. Arrows indicate axons.

Figure 5. Sections from the intraconduit (a, c) and distal stump (b, d) stained with Masson's Trichrome technique. Note that rnt is stained differently from the surrounding intestinal tissue. Arrows indicate axons. rnt: regenerated neural tissue, sim: small intestinal mucosa, sis: small intestinal submucosa. Magnifcations at 10X [above (a, b), Scale bar=100 μm] and 40X [below (c, d), Scale bar=50 μm].

Figure 6. S-100 expression in the sections from proximal stump (a), intraconduit (b) and distal stump (c). Note that surrounding adipose tissue and neural elements in the subintestinal layer were also stained. Magnification at 10X, (Scale bar=100 μm).

Figure 7. Neurofilament expression in the sections from proximal stump (a), intraconduit (b) and distal stump (c). Note that the tangled staining is arranged into a more regular fascicular staining pattern at the distal stump after traversing small intestinal conduit. Magnification at 10X (Scale bar=100 μm).