Chitosan Micro-Grooved Membranes with Increased Asymmetry for the Improvement of the Schwann Cell Response in Nerve Regeneration

Luca Scaccini,Giovanna Gambarotta,Roberta Mezzena,Ilaria Tonazzini,Mariacristina Gagliardi,Alessia De Masi,Marco Cecchini

doi:10.3390/ijms22157901

Abstract

Peripheral nerve injuries are a common condition in which a nerve is damaged, affecting more than one million people every year. There are still no efficient therapeutic treatments for these injuries. Artificial scaffolds can offer new opportunities for nerve regeneration applications; in this framework, chitosan is emerging as a promising biomaterial. Here, we set up a simple and effective method for the production of micro-structured chitosan films by solvent casting, with high fidelity in the micro-pattern reproducibility. Three types of chitosan directional micro-grooved patterns, presenting different levels of symmetricity, were developed for application in nerve regenerative medicine: gratings (GR), isosceles triangles (ISO) and scalene triangles (SCA). The directional patterns were tested with a Schwann cell line. The most asymmetric topography (SCA), although it polarized the cell shaping less efficiently, promoted higher cell proliferation and a faster cell migration, both individually and collectively, with a higher directional persistence of motion. Overall, the use of micro-structured asymmetrical directional topographies may be exploited to enhance the nerve regeneration process mediated by chitosan scaffolds.

Highlights

Peripheral nerve injuries (PNIs), a condition in which a peripheral nerve presents damage due to direct trauma or laceration [1], are a common type of injury around the world, affecting more than one million people every year, with high healthcare and social costs [2,3]
Chitosan membranes were microfabricated and patterned with anisotropic topographies with different levels of axial symmetry by solvent casting on PDMS intermediate molds
The higher freedom and asymmetry in the cell shaping allowed by the scalene triangles (SCA) pattern increased the cell migration and gave a preferential migration direction to the cells, and these are important issues in nerve regenerative applications

Summary

Introduction

Peripheral nerve injuries (PNIs), a condition in which a peripheral nerve presents damage due to direct trauma or laceration [1], are a common type of injury around the world, affecting more than one million people every year, with high healthcare and social costs [2,3]. In the response to nerve injuries, SCs are one of the first components involved, undergoing rapid changes in their phenotype, and proliferating and migrating from the proximal and the distal stump [5] to form the so-called Büngner bands [6]. These structures are fundamental to the regeneration process, providing a track on which neurons can regrow. Artificial scaffolds can offer a new possibility in providing a fast and efficient treatment of nerve injuries They act as a temporary extracellular matrix, providing the structural support needed in the healing process [13]. The biocompatibility of new materials, along with their biodegradability, make artificial scaffolds the perfect candidates for the effective treatment of PNIs [14]

Methods

Results

Discussion

Conclusion