title: Functional recovery of denervated muscle by neurotization using nerve guidance channels.
abstract: Tissue-engineered muscle has been proposed as a means of repairing volumetric muscle defects to restore anatomical and functional recovery. We have previously demonstrated that denervated muscle, which is analogous to engineered muscle construct, can be reinnervated by direct transplantation of host nerve (neurotization) in a rat model. However, the use of this approach is not possible if the length of host nerve is inadequate and cannot be mobilized to the insertion site of the engineered muscle. In this study we investigated whether neurotization coupled with nerve guidance channels would increase the regeneration of neuromuscular junctions (NMJs) in completely denervated muscle and encourage neurofunctional recovery. Seventy-two Lewis rats were evaluated in three groups, a normal control group (n = 8), a denervated group (n = 32) and a neurotization coupled with nerve guidance group (n = 32). Neurofunctional behaviour and histological evaluations were performed at 4, 8, 12 and 20 weeks postoperatively. Extensor postural thrust (EPT) and compound muscle action potential (CMAP) amplitude were significantly improved in the nerve guidance group when compared with the denervated group, even though these values were different from those of the normal control group at 20 weeks postoperation. Regeneration of axons and NMJs was demonstrated histologically in the nerve guidance group. Neurotization coupled with nerve guidance channels leads to regeneration of axons and NMJs in completely denervated muscle. To our knowledge, this is the first report to show that nerve guidance can allow re-innervation in denervated muscle containing long-gap nerve injuries.
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.|Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors: Sung-Bum
authors: SB
authors: Kang
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors: Young Min
authors: YM
authors: Ju
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors: Sang Jin
authors: SJ
authors: Lee
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors: Anthony
authors: A
authors: Atala
authors: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors: James J
authors: JJ
authors: Yoo
mesh_terms: D000818:Animals; D048091:Guided Tissue Regeneration / Q000379:methods*; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000294:innervation*; D009416:Nerve Regeneration; D009469:Neuromuscular Junction / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000502:physiology*
keywords: functional recovery; nerve guidance channel; nerve regeneration; neurotization; reinnervation; tissue-engineered muscle