Cellulose nanomaterials are produced employing a multitude of methodologies including electrospinning, bacterial generation, acid digestion, and a variety of mechanical defibrillation techniques; the morphology of the nanomaterial produced is specific to the production process. Feedstocks range from various forms of woody biomass, to fungi, and have a great impact on the resulting product. The mechanical defibrillation technique, such as that employed in the present work, continuously breaks down cellulose fibers suspended in water via segmentation and defibrillation through grinding and refining. The process is typically operated until a desired level of fines is achieved in the resultant slurry of cellulose nanofiber (CNF), alternatively known as cellulose nanofibril. Mechanical defibrillation processes can be built to produce several liters in a small batch system or up to tons per day in a continuous pilot scale refiner system. In the present work a continuous system was developed with the capacity to produce 14 L of cellulose nanofiber slurry with consistent specifications and in a manner compliant with GMP/GLP protocols in order to be amenable to biomedical applications. The system was constructed within an ISO class 7 cleanroom and refining was performed on bleached softwood pulp suspension in purified water. This manuscript details the continuous grinding system, the processes employed to produce cellulose nanofiber, and characterizes the resultant cellulose nanofiber slurry and sheets formed from the slurry.

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