Biodegradable Bisvinyl Sulfonemethyl-crosslinked Gelatin Conduit Promotes Regeneration after Peripheral Nerve Injury in Adult Rats

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.

The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

“…As a natural protein biopolymer, gelatin possesses some beneficial properties such as availability, cost‐effectiveness, biocompatibility, biodegradability, having no toxic by‐products after enzymatic degradation, stimulation of cellular adhesion, and suitability for drug delivery (Elzoghby, ) and releasing growth factors (Chang et al, ). Previous studies have also shown that the use of gelatin conduits produced by various methods stimulates damaged nerve growth in a rat model (Ko et al, ; Tao et al, ). Moreover, it has been exhibited that NGF immobilized on SC‐loaded gelatin conduits can improve nerve regeneration in a 10‐mm rat sciatic nerve gap model (Chen et al, ).…”

“…The time required for nerve regeneration is at least 2 months (Ko et al, ); however, a study reported a time period of 18 months for nerve regeneration, highlighting that more time is required for the sensory and motor function recovery (Das et al, ).…”

Effects of Electrical Stimulation on Peripheral Nerve Regeneration in a Silicone Rubber Conduit in Taxol-Treated Rats

“…Variables include the types of electrical stimulation (constant/pulse of direct/alternating current), stimulation parameters (frequency and intensity), and the sites of placement of electrodes have also been studied [23]. In the research of nerve conduits, numerous materials have been developed to repair peripheral nerve injury, such as silicone rubber [23,40], gelatin [41], polyglycolic acid [42], polyurethane [41], poly(l-lactide-co-caprolactone) [43], and so on. These nerve conduits are usually designed as a tubular structure, which could provide mechanical orientation and confinement to aid growing nerve fibers.…”

Natural-Based Biomaterials for Peripheral Nerve Injury Repair

“…Nerve regeneration at 8 weeks in a 10 mm rat sciatic nerve defect repaired through this conduit was similar to that obtained using a silicone guide previously tested. Gelatin cross-linking with bisvinylsulfonemethyl reduces gelatin swelling and improves its mechanical properties; moreover, unlike other gelatin conduits, this nerve guide is transparent (Ko et al, 2017).…”