ABSTRACT
BACKGROUND: Peripheral nerve injury can cause significant impairment, and the current methods for facilitating repair, particularly over distances greater than approximately 1 mm, are not entirely effective. Allografts, autografts, and synthetic conduits are three of the most common surgical interventions for peripheral nerve repair; however, each has limitations including poor biocompatibility, adverse immune responses, and the need for successive surgeries. A potential new method for promoting peripheral nerve repair that addresses the shortcomings of current interventions is a biocompatible cellulose nanofibril (CNF) conduit that degrades in-vivo over time. Preliminary testing in multiple animal models has yielded positive results, but more information is needed regarding how the CNF conduit facilitates nutrient and gas flow. RESULTS: The current work employs 3D modelling and analysis via COMSOL Multiphysics® to determine how the CNF conduit facilitates oxygen movement both radially through the conduit walls and axially along the length of the conduit. Various CNF wall permeabilities, conduit lengths, and nerve-to-conduit diameter ratios have been examined; all of which were shown to have an impact on the resultant oxygen profile within the conduit. When the walls of the CNF conduit were modeled to have significant oxygen permeability, oxygen diffusion across the conduit was shown to dominate relative to axial diffusion of oxygen along the length of the conduit, which was otherwise the controlling diffusion mechanism. CONCLUSIONS: The results of this study suggest that there is a complex relationship between axial and radial diffusion as the properties of the conduit such as length, diameter, and permeability are altered and when investigating various locations within the model. At low wall permeabilities the axial diffusion is dominant for all configurations, while for higher wall permeabilities the radial diffusion became dominant for smaller diameters. The length of the conduit did not alter the mechanism of diffusion, but rather had an inverse relationship with the magnitude of the overall concentration profile. As such the modeling results may be employed to predict and control the amount and distribution of oxygenation throughout the conduit, and hence to guide experimental conduit design.
Subject(s)
Peripheral Nerve Injuries , Cellulose , OxygenABSTRACT
Peripheral neuropathy arising from physical trauma is estimated to afflict 20 million people in the United States alone. In one common surgical intervention, neural conduits are placed over the nerve stumps to bridge the gap and create a microenvironment conducive to regeneration. It has been proposed that a biocompatible material such as cellulose nanofiber may serve as a viable conduit material, providing a non-inflammatory and mechanically stable system. Preliminary studies have shown that cellulose nanofiber conduits successfully aid neural regeneration and further, that the dimensions of the conduit relative to the nerve gap have an impact on efficacy in murine models. It has been hypothesized that the reliance of regeneration upon the physical dimensions of the conduit may be related to modified modes of diffusion and/or distances of key cellular nutrients and waste metabolites to/from the injury site. The present work investigates the concentration profile of glucose within the conduit via finite element analysis as a function of the physical dimensions of the conduit. It was determined that the magnitude of glucose diffusion was greater through the conduit walls than through the luminal space between the nerve and the inner wall of the conduit, and that as such radial diffusion is dominant over axial diffusion.
