Reduced Graphene Oxide Fibers Combined with Electrical Stimulation Promote Peripheral Nerve Regeneration

Abstract

Yuanyuan Zhao,1 Yang Liu,1 Cheng Lu,1 Daokuan Sun,2 Shiqi Kang,1 Xin Wang,2,* Laijin Lu1,* 1Department of Hand and Podiatric Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2School of Materials Science and Engineering, Jilin University, Changchun, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Laijin Lu, Department of Hand and Podiatric Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected] Xin Wang, School of Materials Science and Engineering, Jilin University, Changchun, Jilin, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: The treatment of long-gap peripheral nerve injury (PNI) is still a substantial clinical problem. Graphene-based scaffolds possess extracellular matrix (ECM) characteristic and can conduct electrical signals, therefore have been investigated for repairing PNI. Combined with electrical stimulation (ES), a well performance should be expected. We aimed to determine the effects of reduced graphene oxide fibers (rGOFs) combined with ES on PNI repair in vivo.Methods: rGOFs were prepared by one-step dimensionally confined hydrothermal strategy (DCH). Surface characteristics, chemical compositions, electrical and mechanical properties of the samples were characterized. The biocompatibility of the rGOFs were systematically explored both in vitro and in vivo. Total of 54 Sprague-Dawley (SD) rats were randomized into 6 experimental groups: a silicone conduit (S), S+ES, S+rGOFs-filled conduit (SGC), SGC+ES, nerve autograft, and sham groups for a 10-mm sciatic defect. Functional and histological recovery of the regenerated sciatic nerve at 12 weeks after surgery in each group of SD rats were evaluated.Results: rGOFs exhibited aligned micro- and nano-channels with excellent mechanical and electrical properties. They are biocompatible in vitro and in vivo. All 6 groups exhibited PNI repair outcomes in view of neurological and morphological recovery. The SGC+ES group achieved similar therapeutic effects as nerve autograft group (P > 0.05), significantly outperformed other treatment groups. Immunohistochemical analysis showed that the expression of proteins related to axonal regeneration and angiogenesis were relatively higher in the SGC+ES.Conclusion: The rGOFs had good biocompatibility combined with excellent electrical and mechanical properties. Combined with ES, the rGOFs provided superior motor nerve recovery for a 10-mm nerve gap in a murine acute transection injury model, indicating its excellent repairing ability. That the similar therapeutic effects as autologous nerve transplantation make us believe this method is a promising way to treat peripheral nerve defects, which is expected to guide clinical practice in the future.Keywords: peripheral nerve defects, sciatic nerve injury, functional recovery, tissue engineering, conductive materials

Keywords

• peripheral nerve defects
• sciatic nerve injury
• functional recovery
• tissue engineering
• conductive materials