Abstract
In our previous study, we found that gelatin-based materials exhibit good conductivity and are non-cytotoxic. In this study, gelatin was cross-linked with bisvinyl sulfonemethyl (BVSM) to fabricate a biodegradable conduit for peripheral nerve repair. First, BVSM on the prepared conduit was characterized to determine its mechanical properties and contact angle. The maximum tensile strength and water contact angle of the gelatin-BVSM conduits were 23 ± 4.8 MPa and 74.7 ± 9°, which provided sufficient mechanical strength to resist muscular contraction; additionally, the surface was hydrophilic. Cytotoxicity and apoptosis assays using Schwann cells demonstrated that the gelatin-BVSM conduits are non-cytotoxic. Next, we examined the neuronal electrophysiology, animal behavior, neuronal connectivity, macrophage infiltration, calcitonin gene-related peptide localization and expression, as well as the expression levels of nerve regeneration-related proteins. The number of fluorogold-labelled cells and histological analysis of the gelatin-BVSM nerve conduits was similar to that observed with the clinical use of silicone rubber conduits after 8 weeks of repair. Therefore, our results demonstrate that gelatin-BVSM conduits are promising substrates for application as bioengineered grafts for nerve tissue regeneration.
Highlights
We developed a bisvinyl sulfonemethyl (BVSM)-crosslinked gelatin conduit for peripheral nerve repair which is based on our previous studies
Because neuron repair is extremely difficult, it is imperative that conduits fulfill all requirements and environmental conditions for neuron regeneration
Autologous nerve grafts are the most common technique used for peripheral nerve reconstruction
Summary
Ming-You Shie contributed to this work. Correspondence and requests for materials should be addressed to www.nature.com/scientificreports/. Nerve grafts are beneficial for axon recovery because they protect, and guide axon regeneration towards its distal end[4]. They contain cellular materials that expedite the recovery process. Autologous nerve grafts are extracted from the patient’s own body, and by far are the most effective clinical treatment for peripheral nerve trauma[5]. Allograft nerve grafts are not extracted from the patient’s body, but rather from another donor or cadaver[6]. These allogenic nerve grafts, pose immunogenic problems related to antigenicity and increased morbidity associated with immunosuppression[7]. We observed the macrophage infiltration by immunostaining for Iba[1] and CD68 and measured the expression levels of nerve regeneration-related proteins in the regenerated nerves to determine whether the BVSM-crosslinked gelatin conduits could support axonal regeneration and functional restoration
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