Orientated Guidance of Peripheral Nerve Regeneration Using Conduits with a Microtube Array Sheet (MTAS)

Material surface topography has been shown to affect the biological behavior of cells in vitro; however, the in vivo effect on peripheral nerve regeneration has not been explored. Here, we studied the potential of a microtube array sheet (MTAS) with a unique longitudinal surface topography to promote peripheral nerve regeneration efficiency, both in vivo and in vitro. Schwann cells, spinal cord motor neurons, and dorsal root ganglion neurons were seeded on the MTAS to study the effect of the construct on the biological properties and behaviors of neural cells. The MTAS guided the oriented migration of Schwann cells without affecting other critical biological properties, such as proliferation and neurotrophin expression. In addition, the MTAS guided the directed extension of neurites from both types of neurons. Next, we tested the capability of the MTAS to facilitate peripheral nerve regeneration by bridging a 10 mm sciatic nerve defect in rats with a nerve conduit equipped with an MTAS lining. The MTAS significantly promoted peripheral nerve regeneration, as suggested by the greater fiber caliber in the midconduit and the greater abundance of fibers in nerve segment distal to the conduit. Moreover, scanning electron microscopy (SEM) analysis suggested the orientated guidance of nerve regeneration by the MTAS, as indicated by the smaller eccentricity of the nerve fibers and the concordant arrangement of the collagen fiber in both the fibers and the matrix in the MTAS group. Our results collectively suggest that the conduits with the MTAS developed in this study have significant potential for facilitating peripheral nerve regeneration by modifying critical biological behaviors and guiding orientated nerve growth.