Electrospun nanofiber sheets incorporating methylcobalamin promote nerve regeneration and functional recovery in a rat sciatic nerve crush injury model.
Peripheral nerve injury is one of common traumas. Although injured peripheral nerves have the capacity to regenerate, axon regeneration proceeds slowly and functional outcomes are often poor. Pharmacological enhancement of regeneration can play an important role in increasing functional recovery. In this study, we developed a novel electrospun nanofiber sheet incorporating methylcobalamin (MeCbl), one of the active forms of vitamin B12 homologues, to deliver it enough locally to the peripheral nerve injury site. We evaluated whether local administration of MeCbl at the nerve injury site was effective in promoting nerve regeneration. Electrospun nanofiber sheets gradually released MeCbl for at least 8weeks when tested in vitro. There was no adverse effect of nanofiber sheets on function in vivo of the peripheral nervous system. Local implantation of nanofiber sheets incorporating MeCbl contributed to the recovery of the motor and sensory function, the recovery of nerve conduction velocity, and the promotion of myelination after sciatic nerve injury, without affecting plasma concentration of MeCbl.



Methylcobalamin (MeCbl) is a vitamin B12 analog and we previously reported its effectiveness in axonal outgrowth of neurons and differentiation of Schwann cells both in vitro and in vivo. Here we estimated the effect of local administered MeCbl with an electrospun nanofiber sheet on peripheral nerve injury. Local administration of MeCbl promoted functional recovery in a rat sciatic nerve crush injury model. These sheets are useful for nerve injury in continuity differently from artificial nerve conduits, which are useful only for nerve defects. We believe that the findings of this study are relevant to the scope of your journal and will be of interest to its readership.
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Koji
K
Suzuki
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: tanahiro-osk@umin.ac.jp.
Hiroyuki
H
Tanaka
International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 304-0044, Japan.
Mitsuhiro
M
Ebara
International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 304-0044, Japan.
Koichiro
K
Uto
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Hozo
H
Matsuoka
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Shunsuke
S
Nishimoto
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Medical Center for Translational and Clinical Research, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan.
Kiyoshi
K
Okada
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tsuyoshi
T
Murase
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Hideki
H
Yoshikawa
D000818:Animals; D003131:Combined Modality Therapy / Q000295:instrumentation / Q000379:methods; D004058:Diffusion; D004343:Drug Implants / Q000008:administration & dosage / Q000138:chemical synthesis; D004595:Electroplating / Q000379:methods; D004867:Equipment Design; D048091:Guided Tissue Regeneration / Q000295:instrumentation*; D008297:Male; D008567:Membranes, Artificial; D053769:Nanocapsules / Q000737:chemistry / Q000648:ultrastructure; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects* / Q000235:genetics; D059348:Peripheral Nerve Injuries / Q000473:pathology* / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D012399:Rotation; D054457:Tissue Scaffolds; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry
D004343:Drug Implants; D008567:Membranes, Artificial; D053769:Nanocapsules; C019476:mecobalamin; D014805:Vitamin B 12
Electrospun nanofiber sheet; Functional recovery; Methylcobalamin; Myelination; Peripheral nerve regeneration