Experimental in vivo Mouse Sciatic Nerve Model to Study Fibrosis and Nerve Regeneration

Introduction: Fibrosis following nerve injury poses a significant obstacle to effective nerve regeneration, often leading to functional impairment, chronic pain, and reduced quality of life. Existing therapeutic approaches to mitigate fibrosis and promote nerve repair are limited in their efficacy. Biomaterials have emerged as a promising avenue to minimize nerve adhesion to surrounding tissue and neural fibrosis, as well as to enhance nerve regeneration. This study aims to establish a mouse sciatic nerve scarring model that can be used to evaluate the therapeutic value of these biomaterials.

Methods: A gluteal splitting approach was used to identify and lift the sciatic nerve. The tissue surrounding the nerve was cauterized to simulate a poorly vascularized and traumatized nerve bed. The tissue was cooled with saline prior to returning the nerve to its bed. The nerve epineurium was directly irritated rubbing it with cotton-tip applicators and either 100- or 150-grit fine-grade sandpaper. All mice received a contralateral sham surgery and were allowed free cage activity post-operatively. Animals were euthanized at 2 or 4 weeks post-operatively and gross evaluation was performed.

Results: The mice initially exhibited gait impairment post-operatively, indicating successful nerve irritation. Gross evaluation identified significant nerve adhesions at 2- and 4-weeks to the surrounding tissues, which were more severe than the sham control. Within sandpaper grits, 150-grit produced the most scarring to the surrounding tissue.

Conclusion: These findings suggest that this model effectively induces sciatic nerve irritation and adhesion formation, with 150-grit sandpaper causing the most severe scarring to surrounding tissues. This novel model provides an opportunity to study the efficacy of various biomaterials in reducing neural scarring and fibrosis.