A Gelatin/Alginate Double Network Hydrogel Nerve Guidance Conduit Fabricated by a Chemical‐Free Gamma Radiation for Peripheral Nerve Regeneration

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. A novel double‐network (DN) alginate/gelatin hydrogel is fabricated via chemical‐free gamma irradiation and subsequent ionic crosslinking for nerve guidance conduit (NGC) application. The DN hydrogel NGCs demonstrate excellent mechanical stability, biodegradability, and promoted functional nerve recovery in a sciatic defect rat model. The biocompatible DN hydrogel holds promise for peripheral nerve regeneration and other biomedical applications.