Novel Anti-Adhesive CMC-PE Hydrogel Significantly Enhanced Morphological and Physiological Recovery after Surgical Decompression in an Animal Model of Entrapment Neuropathy.

Hideki Urano,Shigeru Kurimoto,Michiro Yamamoto,Tetsuro Ohnisi,Nobuyuki Endo,Katsuyuki Iwatsuki,Hitoshi Hirata,Antal Nógrádi

doi:10.1371/journal.pone.0164572

Hideki Urano, Shigeru Kurimoto + Show 6 more

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https://doi.org/10.1371/journal.pone.0164572

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Abstract

We developed a novel hydrogel derived from sodium carboxymethylcellulose (CMC) in which phosphatidylethanolamine (PE) was introduced into the carboxyl groups of CMC to prevent perineural adhesions. This hydrogel has previously shown excellent anti-adhesive effects even after aggressive internal neurolysis in a rat model. Here, we confirmed the effects of the hydrogel on morphological and physiological recovery after nerve decompression. We prepared a rat model of chronic sciatic nerve compression using silicone tubing. Morphological and physiological recovery was confirmed at one, two, and three months after nerve decompression by assessing motor conduction velocity (MCV), the wet weight of the tibialis anterior muscle and morphometric evaluations of nerves. Electrophysiology showed significantly quicker recovery in the CMC-PE group than in the control group (24.0 ± 3.1 vs. 21.0± 2.1 m/s (p < 0.05) at one months and MCV continued to be significantly faster thereafter. Wet muscle weight at one month significantly differed between the CMC-PE (BW) and control groups (0.148 ± 0.020 vs. 0.108 ± 0.019%BW). The mean wet muscle weight was constantly higher in the CMC-PE group than in the control group throughout the experimental period. The axon area at one month was twice as large in the CMC-PE group compared with the control group (24.1 ± 17.3 vs. 12.3 ± 9 μm2) due to the higher ratio of axons with a larger diameter. Although the trend continued throughout the experimental period, the difference decreased after two months and was not statistically significant at three months. Although anti-adhesives can reduce adhesion after nerve injury, their effects on morphological and physiological recovery after surgical decompression of chronic entrapment neuropathy have not been investigated in detail. The present study showed that the new anti-adhesive CMC-PE gel can accelerate morphological and physiological recovery of nerves after decompression surgery.

Highlights

Postoperative adhesions and perineural scarring are major causes of failure after peripheral nerve surgery [1,2]
The silicone tube was removed from the control and CMC-PE groups to decompress the nerve and the wound was closed in the control group without any adjuvant treatment
The motor conduction velocity (MCV) significantly differed between the control and CMC-PE groups at one month

Summary

Introduction

Postoperative adhesions and perineural scarring are major causes of failure after peripheral nerve surgery [1,2]. 1% to 25% of patients who undergo carpal tunnel release develop symptoms related to residual scar tissue [2,4]. Surrounding tissue adhering to the median nerve can lead to recurrent carpal tunnel syndrome (CTS), which is associated with an extremely high re-recurrence rate [5]. Many surgical techniques have been developed to prevent perineural adhesions, including vein wrapping, muscle flaps and free fat grafts [5,6,7,8,9,10]. We recently developed a novel hydrogel to prevent perineural adhesions, derived from sodium carboxymethylcellulose (CMC) in which phosphatidylethanolamine (PE) was introduced into the carboxyl groups of CMC. The anti-adhesive effect of the hydrogel is excellent even after aggressive internal neurolysis in a rat model [4]

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