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

Abstract

BackgroundScar 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.MethodsThe 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.ResultsTopical 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.ConclusionsTopical 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.

Peripheral Nerve Reconstruction Using Enriched Chitosan Conduits

“…In peripheral nerves, HA has positive effects on peripheral nerve regeneration modulating glial cell adhesion and migration and neuronal sprouting [15][16][17]. Yet, topical application of HA is able to reduce the scar formation and create a more favorable environment for nerve regeneration [37,38].…”

The Role of Pharmacological Agents in Nerve Regeneration after Peripheral Nerve Repair

“…Besides that, this author found better mean conduction velocities (MCVs) and faster functional recovery in HA-treated nerves (0.82 ± 0.08 m/s) compared with nerves treated with saline, in which the MCV was 0.76 ± 0.04 m/s (P < 0.05) [31]. Park et al found that topical application of HA carboxymethylcellulose solutions in rats significantly reduced nerve adherence score and the number of cellular components compared with the saline group (control group) (P < 0.05) [70]. The authors concluded that HA carboxymethylcellulose solutions improved nerve regeneration and reduced perineural scar formation and adhesion after sciatic nerve repair [70].…”

“…Use of the hyaluronic acid-carboxymethylcellulose membrane Seprafilm as a solid anti-adhesion barrier agent is one of the therapeutic approaches used to reduce postoperative scar formation and is effective in promoting peripheral nerve regeneration at the repair site [69]. In addition, HA-carboxymethylcellulose solutions improve nerve regeneration and reduce perineural scar formation and adhesion after sciatic nerve repair [70]. It has been confirmed that direct application of HA-carboxymethylcellulose in transected nerves may limit axonal outgrowth by contact with regenerating axons; therefore, HAcarboxymethylcellulose barriers may prove to be a tool to prevent neuroma formation through inhibiting axonal growth [71].…”

“…Ozgenel [31] and Park et al [70] Stimulator of interleukin-1 (IL-1) production, which affects (decreases) fibroblast proliferation and collagenase production Hiro et al [30] Tacrolimus (FK506) Neuroprotective role via reduction of scar formation Through encouraging fibroblast apoptosis, it contributes to the suppression of fibroblast proliferation. Fibroblast apoptosis by tacrolimus involves c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase Que et al [94] Neuroregenerative role FK506-FKBP12 interaction may lead to a neuroregenerative effect through increased neuronal expression of growth cone-associated protein GAP-43 that probably occurs through inactivation of neuronal nitric synthetase…”

“…Methylprednisolone Neuroprotective role By its inhibition of CD3-positive inflammatory cell infiltration in local tissue and consequently recruitment of macrophages Feng and Yuan [123] Anti-inflammatory effects Through inhibition of oxygen-free radical-induced lipid peroxidation Hall [124] Vitamin B12 Nerve regeneration Owing to axoplasm flow within the neuraxon, in order to normalise the neuraxon's skeleton protein transportation as well as accelerating the formation of the myelin sheath Wang et al [129] Neuroprotectant Through increasing the number of Schwann cells and myelinated nerve fibres, and the diameter of axons Lopatina et al [132] Through antioxidant properties, because it is also a good scavenger of reactive oxygen species tion of the effects of these pharmacological agents in the prevention of scar formation and nerve regeneration in experimental animals is performed by electrophysiological measurements and through assessing functional recovery, whereas after sacrificing the animals, other methods have been used, such as macroscopic, histomorphometric, immunohistochemical and biomechanical techniques [70,91,98,99]. Ozgenel found that nerves treated with HA have a significant reduction in perineural thickness compared to nerves treated with just saline (P < 0.05).…”