Abstract

Peripheral nerve defects, but not artificial nerves, are repaired by endogenous cells. We examined cell activity during the repair process in the presence of autologous nerves and artificial preparations in order to guide future artificial nerve fabrication. PLGA tubes, nerve scaffolds comprising a PLGA tube plus 6,000 fibroin fibers, or autologous nerves were implanted into 10 mm rat sciatic nerve defects (n = 60 per group). Over a period of 1-20 weeks after nerve grafting, sections were stained and imaged to distinguish the cell types present and we quantified the recovery of motor and sensory function in the surgically implanted limb. We observed a decreasing trend in inflammatory cell and fibroblast counts over time which ranked in magnitude as: (PLGA group > nerve scaffold > autologous nerve> sham) and an opposite trend in Schwann cell counts. Differences in withdrawal time from hot water and static sciatic index (SSI) indicated that, after repair, sensory and motor function were best in the sham group, followed by the autologous group, the nerve scaffold group, and the PLGA group. These findings indicate that the inflammatory reaction is significant in the first two weeks after nerve grafting, followed by the rebirth of fibroblasts and Schwann cells, which guide axon regeneration. This inflammatory response was a fundamental stage of peripheral defect repair, but a weaker inflammatory response corresponded to better recovery of sensorimotor functional.

Highlights

  • IntroductionPeripheral nerve diseases [1,2,3,4,5,6,7,8,9,10,11] commonly seen in the clinic include peripheral nerve sheath tumors [12,13,14,15], optic nerve injury [16, 17], peripheral nerve chronic constriction injury [18], and peripheral nerve defects

  • Inflammatory responses require inflammatory cells to migrate within and through the vasculature [25]; in addition, integrins are associated with the migration of eosinophils and the activation of macrophages [26], and fibroblasts and Schwann cells are required for nerve regeneration [1, 3, 11]

  • Observation of cell activity during the process of peripheral nerve defect repair may help guide the preparation of an artificial nerve

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Summary

Introduction

Peripheral nerve diseases [1,2,3,4,5,6,7,8,9,10,11] commonly seen in the clinic include peripheral nerve sheath tumors [12,13,14,15], optic nerve injury [16, 17], peripheral nerve chronic constriction injury [18], and peripheral nerve defects. Clinical [19, 20] and experimental [21,22,23] research has been carried out to find ways to treat peripheral nerve diseases. The development of artificial nerve grafts to replace autologous nerve grafts is the focus of considerable current research. Inflammatory responses require inflammatory cells to migrate within and through the vasculature [25]; in addition, integrins are associated with the migration of eosinophils and the activation of macrophages [26], and fibroblasts and Schwann cells are required for nerve regeneration [1, 3, 11]. Observation of the performance of inflammatory cells, Schwann cells, and fibroblasts in the process of peripheral nerve defect repair will guide the development of future artificial nerve preparations

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