Patterning the Inside of Polymer Tubes to Guide Nerve Regeneration

Abstract

Clinically approved nerve regeneration conduits for peripheral nerve and spinal cord injuries lack the ability to directionally guide neurite extension in forming proper connections between the ends of a transected nerve. Techniques to chemically pattern medically relevant polymers to template ECM assembly and guide neurite extension have been developed. In this study, these patterning methods were translated to the inner surfaces of 1.5 mm internal diameter, 13 mm long poly(caprolactone fumarate) (PCLF) peripheral nerve guidance conduit tubes that were optimized for the rat sciatic nerve animal model. A shadow mask was developed to control chemical vapor deposition (CVD) of a volatile zirconium complex, zirconium tetra(tert-butoxide), onto the inner surface of these tubes. Subsequent mild thermolysis and immersion in a solution of 1,4-diphosphonobutane made cell adhesive-patterned stripes (ZrO2-SAMP) on these surfaces. Patterning was characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). Patterned tubes were furnished for cell studies (Schwarzbauer Lab, Princeton University) and for an in vivo animal test (Windebank Lab, Mayo Clinic). Exploration studies were conducted to pattern ZrO2-SAMP on oligo[poly(ethylene glycol) fumarate] (OPF) hydrogels, which have been optimized for spinal cord compatibility. Soft lithography microcontact printing techniques on PET were performed as a proof of concept. Future studies will develop these methods for OPF hydrogels to prepare devices that may guide nerve regeneration towards functional recovery.