A reduced graphene oxide functionalized electrospun nerve wrap: Amalgamating electrical and biochemical cues to enhance nerve regeneration in median nerve injury model

Abstract

Nerve injuries leads to severe impairment of target tissue and standard treatment approaches from surgery to electrical stimulation are complex, yielding only brief relief. The current study addresses such limitations with reduced graphene oxide (rGO) functionalized “Electroband”. We attempt to conjugate electrical cues in the nerve wrap with in-situ electrical stimulation in a median nerve injury model in rats, underlining the significance of combinatorial therapy for nerve regeneration. “Electroband” targets three critical aspect of nerve regeneration: neuroprotection, neuroregeneration and neuroplasticity at single stroke. The nanofibrous extracellular matrix mimicking nature of “Electroband” assisted in reconciling the injured niche by preventing anoikis, exerting neuroprotective effect as depicted with aligned growth of compressed nerve fibers. The rGO functionalization coupled with intraoperative electrical stimulation of 3 V @ 20 Hz for 10 min aided in propelling the injured nerve to denervated target, prompting fascicular growth of nerve fibers, targeting neuroplasticity. The nerve growth factor incorporation enhanced the bioactivity of scaffold, augmenting regeneration leading to exuberant growth and myelination of nascent nerve tracts. These results led to significant improvement in electrophysiological recordings with 30–32 mV CMAP value (80% recovery) in combinatorial therapy group as compared to 10–11 mV in negative controls and 13–15 mV in animals with individual therapy. We therefore, report 80% regain in muscular strength within 8 weeks of implantation with combinatorial therapy as assessed with behavioural paw gripping and scratch tape assay. Thus, we successfully demonstrated the pre-clinical efficacy of “Electroband”, reducing the time and frequency of electrical stimulation currently in clinical practice.