Abstract Nerve guidance conduits (NGCs) are widely developed using various materials for the functional repair of injured or diseased peripheral nerves. Especially, hydrogels are considered highly suitable for the fabrication of NGCs due to their beneficial tissue‐mimicking characteristics (e.g., high water content, softness, and porosity). However, the practical applications of hydrogel‐based NGCs are hindered due to their poor mechanical properties and complicated fabrication processes. To bridge this gap, a novel double‐network (DN) hydrogel using alginate and gelatin by a two‐step crosslinking process involving chemical‐free gamma irradiation and ionic crosslinking, is developed. DN hydrogels (1% alginate and 15% gelatin), crosslinked with 30 kGy gamma irradiation and barium ions, exhibit substantially improved mechanical properties, including tensile strength, elastic modulus, and fracture stain, compared to single network (SN) gelatin hydrogels. Additionally, the DN hydrogel NGC exhibits excellent kink resistance, mechanical stability to successive compression, suture retention, and enzymatic degradability. In vivo studies with a sciatic defect rat model indicate substantially improved nerve function recovery with the DN hydrogel NGC compared to SN gelatin and commercial silicone NGCs, as confirm footprint analysis, electromyography, and muscle weight measurement. Histological examination reveals that, in the DN NGC group, the expression of Schwann cell and neuronal markers, myelin sheath, and exon diameter are superior to the other controls. Furthermore, the DN NGC group demonstrates increased muscle fiber formation and reduced fibrotic scarring. These findings suggest that the mechanically robust, degradable, and biocompatible DN hydrogel NGC can serve as a novel platform for peripheral nerve regeneration and other biomedical applications, such as implantable tissue constructs.
In this study, we designed a cell-adhesive poly(ethylene glycol) (PEG)-based hydrogel that simultaneously provides topographical and electrical stimuli to C2C12 myoblasts. Specifically, PEG hydrogels with microgroove structures of 3 μm ridges and 3 μm grooves were prepared by micromolding; in situ polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) was then performed within the micropatterned PEG hydrogels to create a microgrooved conductive hydrogel (CH/P). The CH/P had clear replica patterns of the silicone mold and a conductivity of 2.49 × 10-3 S/cm, with greater than 85% water content. In addition, the CH exhibited Young's modulus (45.84 ± 7.12 kPa) similar to that of a muscle tissue. The surface of the CH/P was further modified via covalent bonding with cell-adhesive peptides to facilitate cell adhesion without affecting conductivity. An in vitro cell assay revealed that the CH/P was cytocompatible and enhanced the cell alignment and elongation of C2C12 myoblasts. The microgrooves and conductivity of the CH/P had the greatest positive effect on the myogenesis of C2C12 myoblasts compared to the other PEG hydrogel samples without conductivity or/and microgrooves, even in the absence of electrical stimulation. Electrical stimulation studies indicated that the combination of topographical and electrical cues maximized the differentiation of C2C12 myoblasts into myotubes, confirming the synergetic effect of incorporating microgroove surface features and a conductive PEDOT component into hydrogels.
Electroconductive materials, such as conductive polymers and carbon-nanomaterials, have been studied since the 1970s for use in a broad range of applications. These materials showcase electrical properties that are similar to those of commonly used metals, while providing other benefits such as processing flexibility, ability to modify, and ease of synthesis. Conductive polymers (e.g., polypyrrole, polythiophene, polyaniline) as well as carbon-based nanomaterials (e.g., graphene, fullerenes) are organic in nature. This makes them ideal candidates to be augmented to create biocompatible materials while maintaining electroactive properties at functional levels that match endogenous electrical tissue activity. In this review, we focus on the uses of these electroconductive materials in the context of the nervous system, specifically recent studies in the brain, eye, ear, spinal cord, and peripheral nerve. We also highlight in vivo studies and clinical trials, as well as provide a brief look at emerging electroconductive materials.
Bioelectrodes are key components of electronic devices that efficiently mediate electrical signals in biological systems. However, conventional bioelectrodes often undergo biofouling associated with non-specific proteins and cell adhesion on the electrode surfaces, which leads to seriously degraded electrical and/or electrochemical properties. Hence, a facile and effective method to modify the surface of bioelectrodes is required to introduce anti-biofouling properties and improve performance. Here, we report an electrochemical surface modification of a bioelectrode via co-deposition of hyaluronic acid (HA) and polydopamine (PDA). The electrochemical polymerization and deposition of PDA offered simple and effective incorporation of highly hydrophilic and anti-fouling HA to the electrode surfaces, with no substantial increase in impedance. HA-incorporated PDA (PDA/HA)-modified electrodes displayed significant resistance to non-specific protein adsorption and the adhesion of fibroblasts. In addition, 4-week subcutaneous implantation studies revealed that the modified electrodes attenuated scar tissue formation compared with that induced by unmodified bare electrodes. This simple and effective electrochemical surface modification could be further employed for various implantable bioelectrodes (e.g., prosthetics and biosensors) and could extend their bioelectronic applications.
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