Abstract
BackgroundAlthough many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways. In the last few decades tissue engineering has opened the door to new approaches;: however most of them make use of rigid channel guides that may cause cell loss due to the lack of physiological local stresses exerted over the nervous tissue during patient's movement. Electrospinning technique makes it possible to spin microfiber and nanofiber flexible tubular scaffolds composed of a number of natural and synthetic components, showing high porosity and remarkable surface/volume ratio.ResultsIn this study we used electrospun tubes made of biodegradable polymers (a blend of PLGA/PCL) to regenerate a 10-mm nerve gap in a rat sciatic nerve in vivo. Experimental groups comprise lesioned animals (control group) and lesioned animals subjected to guide conduits implantated at the severed nerve stumps, where the tubular scaffolds are filled with saline solution. Four months after surgery, sciatic nerves failed to reconnect the two stumps of transected nerves in the control animal group. In most of the treated animals the electrospun tubes induced nervous regeneration and functional reconnection of the two severed sciatic nerve tracts. Myelination and collagen IV deposition have been detected in concurrence with regenerated fibers. No significant inflammatory response has been found. Neural tracers revealed the re-establishment of functional neuronal connections and evoked potential results showed the reinnervation of the target muscles in the majority of the treated animals.ConclusionCorroborating previous works, this study indicates that electrospun tubes, with no additional biological coating or drug loading treatment, are promising scaffolds for functional nervous regeneration. They can be knitted in meshes and various frames depending on the cytoarchitecture of the tissue to be regenerated. The versatility of this technique gives room for further scaffold improvements, like tuning the mechanical properties of the tubular structure or providing biomimetic functionalization. Moreover, these guidance conduits can be loaded with various fillers like collagen, fibrin, or self-assembling peptide gels or loaded with neurotrophic factors and seeded with cells. Electrospun scaffolds can also be synthesized in different micro-architectures to regenerate lesions in other tissues like skin and bone.
Highlights
Many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways
Scaffold characterization and gross findings A novel electrospun biodegradable micro- and nanofiber scaffold was developed by electrospinning solutions of PCL and PCL/PLGA
A fibrous structure was preferred over stiff continuous tubes to obtain nerve guides with high flexibility, high porosity, high surface/volume ratio favouring protein adsorption and fibrous structures that were easy to suture to the sciatic nerve stumps
Summary
Many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways. In the last few decades tissue engineering has opened the door to new approaches;: most of them make use of rigid channel guides that may cause cell loss due to the lack of physiological local stresses exerted over the nervous tissue during patient's movement. If substantial loss of nervous tissue occurs, clinical treatment involves donor nerves obtained from a second operative site of the patient, such as an autologous nerve graft, vein graft, or arterial graft This method is far from being the gold standard though, because its benefits have to be counterbalanced by function loss at the donor sites, formation of potential painful neuromas, structural differences between donor and recipient grafts preventing a successful regeneration, and shortage of graft material for extensive repair [1,2].
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