Closing the Gap: Bridging Peripheral Sensory Nerve Defects with a Chitosan-Based Conduit a Randomized Prospective Clinical Trial

Abstract

Introduction: If tensionless nerve coaptation is not possible, bridging the resulting peripheral nerve defect with an autologous nerve graft is still the current gold standard. The concept of conduits as an alternative with different materials and architectures, such as autologous vein conduits or bioartificial nerve conduits, could not replace the nerve graft until today. Chitosan, as a relatively new biomaterial, has recently demonstrated exceptional biocompatibility and material stability with neural lineage cells. The purpose of this prospective randomized clinical experiment was to determine the efficacy of chitosan-based nerve conduits in regenerating sensory nerves in the hand. Materials and methods: Forty-seven patients with peripheral nerve defects up to 26 mm distal to the carpal tunnel were randomized to receive either a chitosan conduit or an autologous nerve graft with the latter serving as the control group. Fifteen patients from the conduit group and seven patients from the control group were available for a 12-month follow-up examination. The primary outcome parameter was tactile gnosis measured with two-point discrimination. The secondary outcome parameters were Semmens Weinstein Monofilament Testing, self-assessed pain, and patient satisfaction. Results: Significant improvement (in static two-point discrimination) was observed six months after trauma (10.7 ± 1.2 mm; p < 0.05) for chitosan-based nerve conduits, but no further improvement was observed after 12 months of regeneration (10.9 ± 1.3 mm). After six months and twelve months, the autologous nerve graft demonstrated comparable results to the nerve conduit, with a static two-point discrimination of 11.0 ± 2.0 mm and 7.9 ± 1.1 mm. Semmes Weinstein Filament Testing in the nerve conduit group showed a continuous improvement over the regeneration period by reaching from 3.1 ± 0.3 after three months up to 3.7 ± 0.4 after twelve months. Autologous nerve grafts presented similar results: 3.3 ± 0.4 after three months and 3.7 ± 0.5 after twelve months. Patient satisfaction and self-reported pain levels were similar between the chitosan nerve conduit and nerve graft groups. One patient required revision surgery due to complications associated with the chitosan nerve tube. Conclusion: Chitosan-based nerve conduits are safe and suitable for bridging nerve lesions up to 26 mm in the hand. Tactile gnosis improved significantly during the early regeneration period, and functional outcomes were similar to those obtained with an autologous nerve graft. Thus, chitosan appears to be a sufficient substitute for autologous nerve grafts in the treatment of small nerve defects in the hand.

Development of Two-Layer Hybrid Scaffolds Based on Oxidized Polyvinyl Alcohol and Bioactivated Chitosan Sponges for Tissue Engineering Purposes

“…Chitosan is a polysaccharide broadly used for supporting peripheral nerve regeneration, fulfilling the recommendations for a nerve conduit material [ 22 ]. In fact, chitosan-based devices show adequate biodegradability, biocompatibility, neglectable toxicity, and suitable biological absorptivity; excellent antibacterial activity is also reported [ 22 , 23 , 24 , 25 ]. In addition, chitosan proved beneficial in guiding Schwann cells’ orientation, preserving the survival and differentiation of neuronal cells (commercial device, Reaxon ® ).…”

“…In addition, chitosan proved beneficial in guiding Schwann cells’ orientation, preserving the survival and differentiation of neuronal cells (commercial device, Reaxon ® ). All this evidence highlights its potential to serve as a valid alternative to autografts [ 22 , 24 , 25 ]. However, although distinguished as a highly promising material for NCs, positive outcomes are mainly related to short gaps, whereas its contribution in long gap nerve injury repair still needs to be clarified due to conflicting results [ 22 , 26 ].…”

Schmerzen nach Verwendung eines Chitosan-Neurotubes bei Medianusverletzung

“…Von der Anwendung als Ummantelung muss die Verwendung als Überbrückung (Interponat) abgegrenzt werden. Für digitale Nerven wurde gezeigt, dass Interponate aus Chitosan autologen Nerveninterponaten nicht unterlegen sind 4 . Von einer Verwendung als Interponat bei größeren Nerven wird derzeit abgeraten.…”

Management of peripheral nerve injuries using natural based biomaterials and their derivatives: Advances and prospective

“…10 When treating severe nerve injury, autologous nerve grafting is the treatment of choice, especially in cases where there are large gaps or extensive scars that prevent the proximal nerve stump from regenerating and being innervated. 11 However, functional recovery during allogeneic nerve grafting is frequently restricted due to the absence of effective reinnervation that occurs after the procedure. 12,13 Many synthetic nerve guidance conduits (NGCs) have been made from polymeric materials such as poly(L-lactide), poly (lactic glycolic acid), poly(caprolactone), polyamides, and others.…”

“…This personalized medicine approach marks a significant stride towards optimizing treatment outcomes by accounting for the individualized nature of peripheral nerve injuries. 11 Delving into the intrinsic properties of these biomaterials, including their biocompatibility, bioactivity, and regenerative potential, the review segment comprehensively outlines the rich spectrum of natural-based biomaterials and their applicability in nerve regeneration. The subsequent sections meticulously dissect recent advancements in peripheral nerve injury management, emphasizing breakthroughs, clinical trials, and innovative technologies that showcase the efficacy of these biomaterials in promoting nerve repair.…”