Nerve guides manufactured from photocurable polymers to aid peripheral nerve repair

Abstract

The peripheral nervous system has a limited innate capacity for self-repair following injury, and surgical intervention is often required. For injuries greater than a few millimeters autografting is standard practice although it is associated with donor site morbidity and is limited in its availability. Because of this, nerve guidance conduits (NGCs) can be viewed as an advantageous alternative, but currently have limited efficacy for short and large injury gaps in comparison to autograft. Current commercially available NGC designs rely on existing regulatory approved materials and traditional production methods, limiting improvement of their design. The aim of this study was to establish a novel method for NGC manufacture using a custom built laser-based microstereolithography (μSL) setup that incorporated a 405 nm laser source to produce 3D constructs with ∼ 50 μm resolution from a photocurable poly(ethylene glycol) resin. These were evaluated by SEM, in vitro neuronal, Schwann and dorsal root ganglion culture and in vivo using a thy-1-YFP-H mouse common fibular nerve injury model. NGCs with dimensions of 1 mm internal diameter × 5 mm length with a wall thickness of 250 μm were fabricated and capable of supporting re-innervation across a 3 mm injury gap after 21 days, with results close to that of an autograft control. The study provides a technology platform for the rapid microfabrication of biocompatible materials, a novel method for in vivo evaluation, and a benchmark for future development in more advanced NGC designs, biodegradable and larger device sizes, and longer-term implantation studies.

Additive manufactured biodegradable poly(glycerol sebacate methacrylate) nerve guidance conduits

“…The genetic modification enabling this fluorescence has no influence upon regeneration and no harmful effects have been reported [33]. In terms of axon visualization, graft repair controls were comparable to previous studies, with areas of axon disruption located between the graft and nerve ends and fairly organized axons within the graft tissue itself [31]. PGSm repairs displayed observably fewer axons overall, with axons occupying a thin strip between nerve endings -correlating to the above observations of the harvested tissue.…”

“…This issue was overcome by using laser cutting post-production, creating precisely designed highly reproducible conduits. The NGCs were elastic in nature, and when bent did not fracture or kink, making them easier to handle surgically than previously studied stiff polyethylene glycol (PEG) conduits, which exhibited a stiffness of 470 MPa as compared to 3.2 MPa for the PGSm NGCs in this study [31].I ti s reported that kinking of NGC's may occlude the conduit lumen, hindering axonal regeneration, particularly with larger gap injuries [40]. It is therefore advantageous for a conduit to flex with body movements before kinking.…”

“…In vivo implantation, was carried out using our previously reported techniques [31], described briefly below.…”

“…Image acquisition methodologies were adapted from techniques developed in our group reported [31,32] and are described in brief below. A fluorescent microscope (Axioplan2 Imaging; Zeiss, Welwyn Garden City, UK), fitted with a Qimaging Retiga 1300R camera, was used to acquire images of nerve.…”

Emergence of Bioprinting in Tissue Engineering: A Mini Review

“…The printing process did not affect the viability of the RGC/glial cells in culture, and retain the growth promoting properties of the glial cells. Pateman et al 55 printed PEG-based fine nerve guidance conduit through microstereo lithographic technique for nerve repair studies. In addition, 4D bioprinting has also been applied in several studies, for example bone tissue, 56 vascular tissue 21,41,57,58 etc.…”