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.

Background Peripheral nerve injury can cause significant impairment, and the current methods for facilitating repair, particularly over distances greater than approximately 1mm, 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.

No abstract

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes. Proactive treatment options remain limited, largely due to a lack of sensitive and convenient diagnostics, especially early in disease progression or specifically for small fiber neuropathy (SFN), the dying back of distal small diameter nerves. Here, we report on the design, testing, and validation of a novel medical diagnostic device for the functional assessment of small fiber nerves: an electrically conductive needle array designed to record nerve activity signals in the skin and transdermal tissues, which we call the DEN (Detecting Early Neuropathy). DEN recordings were validated across a time course of high fat diet-induced DPN in mice. Based on preclinical mouse data, the device was then adapted to obtain recordings in human tissue. DEN recordings successfully recorded various types of neural activity. New functional diagnostic tools like DEN offer a promising outlook for patients needing an earlier and more sensitive diagnosis of SFN/DPN, which will allow for earlier and more effective treatment options such as implementation of glucose regulation strategies.