Bioengineered glial strands for nerve regeneration

Abstract

Nerve guide implants approved for human application in the peripheral nervous system generally fail to bridge lesion gaps longer than 2cm and cannot match the clinical performance of autologous nerve transplants. Since current synthetic implants are simply hollow tubes, we aim to recreate the native microarchitecture of nerves inside the tubular implants. Most importantly, in the regenerating nerve, dedifferentiated Schwann cells align to form thousands of long glial strands, which act as guiding structures for the regrowing axons. In order to artificially induce the formation of Schwann cell strands, 28μm thick, endless poly-p-dioxanone filaments (PDO) were synthesized with longitudinal grooves. A polycationic coating on the PDO filaments rendered the polymer surface cell-permissive and induced the growth of highly oriented Schwann cells with polarized expression of N-cadherin at cell–cell contact sites. In vitro cell proliferation on three-dimensional PDO filaments was significantly increased in comparison to planar PDO substrates. Time lapse video recordings revealed high Schwann cell motility, which is advantageous for the repopulation of cell-free implants after implantation. In a pilot study we employed a novel microsurgical technique in vivo. All axon fascicles were selectively dissected from sciatic rat nerves, and the remaining epineural tube was filled with hundreds of PDO filaments. Histological analysis 6 weeks postoperatively showed no fibrosis or encapsulation but instead longitudinal cell alignment and axonal regrowth. The data suggest that the addition of microstructured PDO filaments to the lumen of synthetic tubular implants might significantly improve performance.