Clin Orthop Surg.  2011 Dec;3(4):315-324. 10.4055/cios.2011.3.4.315.

Effect of Hyaluronic Acid-Carboxymethylcellulose Solution on Perineural Scar Formation after Sciatic Nerve Repair in Rats

• Park JS
• Lee JH
• Han CS
• Chung DW
• Kim GY

• KMID: 1097170
• DOI: http://doi.org/10.4055/cios.2011.3.4.315

Abstract

BACKGROUND
Scar tissue formation is the major cause of failure in peripheral nerve surgery. Use of a hyaluronic acid-carboxymethylcellulose (HA-CMC) membrane (Seprafilm) as a solid anti-adhesion barrier agent is one of the therapeutic approaches to reduce postoperative scar tissue formation. However, a solid membrane may not be suitable for repair of a weak peripheral nerve site. This study examined the effect of HA-CMC solution on perineural scar formation after peripheral nerve repair in rats.
METHODS
The sciatic nerves of 40 rats were transected and then immediately repaired using 10-0 nylon. The nerves were divided randomly into two groups. Saline and HA-CMC solution were applied topically to the nerve repair sites in the control and experimental groups, respectively. Reoperation was performed at 3, 6, 9, and 12 weeks to assess scar tissue formation. The assessment included the quality of wound healing, presence of perinueral adhesion, cellular components of the scar tissue, thickness of the scar tissue and histomorphological organization of the repair site.
RESULTS
Topical application of the HA-CMC solution significantly decreased the macroscopic nerve adherence score and the numbers of the cellular components such as fibroblasts and inflammatory cells (p < 0.05, Mann-Whitney U-test). The scar tissue formation index was significantly lower in the experimental group at 12 weeks than that in the control group (p < 0.05, Mann-Whitney U-test). The grading scores of the histomorphological axonal organization at the repair site were significantly higher in the experimental group than those in the control group at 12 weeks (p < 0.05, Mann-Whitney U-test). No evidence of wound dehiscence or inflammatory reactions against the HA-CMC solution was noted.
CONCLUSIONS
Topical application of a HA-CMC solution is effective in reducing the perineural scar formation and adhesion after sciatic nerve repair in rats, and is effective in promoting peripheral nerve regeneration at the repair site.

Keyword

Hyaluronic acid; Carboxymethylcellulose; Peripheral nerve; Scar formation; Adhesion

MeSH Terms

Animals
Carboxymethylcellulose Sodium/therapeutic use
Cicatrix/*prevention & control
Drug Combinations
Hyaluronic Acid/*therapeutic use
*Membranes, Artificial
Postoperative Complications/*prevention & control
Rats
Rats, Sprague-Dawley
Sciatic Nerve/*surgery
Solutions

Figure

• 

  Fig. 1 Schematic diagram of the assessment of the cellular components in the scar tissue. The mean value of the cellular components of each quadrant in the extraneural scar tissue was calculated at × 400 magnification.

• 

  Fig. 2 Schematic diagram of the scar tissue formation index. The scar tissue with the largest thickness was normalized by dividing it by the nerve diameter. Scar tissue formation index = the ratio of the thickness of the extraneural scar tissue to the nerve diameter (a/b).

• 

  Fig. 3 Results of the macroscopic assessment of nerve adherence. The scores of the experimental group were significantly lower than the scores of the control group (*p < 0.05).

• 

  Fig. 4 Results of the fibroblast counts. The fibroblast counts of the experimental group were significantly lower than the fibroblast counts of the control group (*p < 0.05).

• 

  Fig. 5 Results of the inflammatory cell counts. The inflammatory cell counts of the experimental group were significantly lower than the inflammatory cell counts of the control group (*p < 0.05).

• 

  Fig. 6 Photomicrographs showing the longitudinal sections of the sciatic nerves following cut and repair with saline (A, B) and with the hyaluronic acid-carboxymethylcellulose (HA-CMC) solution (C, D) at 3 weeks after surgery. The sections were stained with H&E (A, C) and with Masson's trichrome (B, D). Original magnification was × 40. In the nerves treated with saline, a moderate inflammatory cell infiltration and the interlacing or whirling appearance of axons were demonstrated at the repair site (A). In the nerves treated with the HA-CMC solution, a mild inflammatory cell infiltration and the whirling and focal parallel appearance of axons were demonstrated at the repair site (C). The thickness of the blue-stained collagen depositions surrounding the nerve in the saline group was similar to that in the HA-CMC solution group (B, D).

• 

  Fig. 7 Photomicrographs showing the longitudinal sections of the sciatic nerves following cut and repair with saline (A, B) and with the hyaluronic acid-carboxymethylcellulose (HA-CMC) solution (C, D) at 6 weeks after surgery. The sections were stained with H&E (A, C) and with Masson's trichrome (B, D). Original magnification was × 40. In the nerves treated with saline, a moderate inflammatory cell infiltration and an interlacing or whirling appearance of axons were demonstrated at the repair site (A). However, in the nerves treated with HA-CMC solution, a mild inflammatory cell infiltration and a relatively parallel appearance of axons were demonstrated at the repair site (C). The thickness of the blue-stained collagen depositions surrounding the nerve in the saline group was thicker than that in the HA-CMC solution group (B, D).

• 

  Fig. 8 Photomicrographs showing the longitudinal sections of the sciatic nerves following cut and repair with saline (A, B) and with the hyaluronic acid-carboxymethylcellulose (HA-CMC) solution (C, D) at 9 weeks after surgery. The sections were stained with H&E (A, C) and with Masson's trichrome (B, D). Original magnification was × 40. In the nerves treated with saline, the relatively parallel appearance of axons with focal interlacing was observed at the repair site (A). However, in the nerves treated with the HA-CMC solution, a minimal inflammatory cell infiltration and a mostly parallel appearance of axons were demonstrated at the repair site (C). The thickness of the blue-stained collagen depositions surrounding the nerve in the HA-CMC solution group was less than that in the saline group (B, D).

• 

  Fig. 9 Photomicrographs showing the longitudinal sections of the sciatic nerves following cut and repair with saline (A, B) and with the hyaluronic acid-carboxymethylcellulose (HA-CMC) solution (C, D) at 12 weeks after surgery. The sections were stained with H&E (A, C) and with Masson's trichrome (B, D). Original magnification was × 40. In the nerves treated with saline, a mild inflammatory cell infiltration and a mostly parallel appearance of axons were observed at the repair site (A). However, in the nerves treated with the HA-CMC solution, a minimal inflammatory cell infiltration and a normal looking appearance of axons were demonstrated at the repair site (C). Compared to the HA-CMC solution group, the marked deposition of collagen surrounding the nerve was demonstrated in the saline group (B, D).

• 

  Fig. 10 Results of the scar tissue formation index. The scar tissue formation index was significantly decreased in the experimental group at 12 weeks as compared with that in the control group (*p < 0.05).

• 

  Fig. 11 Grading scores of the histomorphological axonal organization at the repair site. The scores were significantly higher in the experimental group than that in the control group at 12 weeks (*p < 0.05).

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