Enhanced in vivo survival of Schwann cells by a synthetic oxygen carrier promotes sciatic nerve regeneration and functional recovery.
Local hypoxia in the early stages of peripheral nerve injury is a challenge for axonal regeneration. To address this issue, perfluorotributylamine (PFTBA)-based oxygen carrying fibrin hydrogel was prepared and injected into Schwann cell (SC)-seeded collagen-chitosan conduits to increase oxygen supply to SCs within the conduits. The conduit containing PFTBA-SC gel was then applied to bridge a 15-mm sciatic nerve defect in rats. It was observed that most of the GFP-labeled SCs initially seeded in the PFTBA hydrogel remained alive for approximately 28 days after their in vivo implantation. The number of SCs was significantly higher in the PFTBA-SC scaffold than that in the SC scaffold without PFTBA. In addition, nerve regeneration and functional recovery were examined after nerve injury repair. We found that the PFTBA-SC scaffold was capable of promoting axonal regeneration and remyelination of the regenerated axons. Further studies showed the PFTBA-SC scaffold was able to accelerate the recovery of motor and sensory function of the regenerating nerves. Electrophysiological analysis showed area under the curve of compound muscle action potential and nerve conduction velocity were also improved, and gastrocnemius muscle atrophy was partially reversed by PFTBA-SC scaffold. Furthermore, microvessel density analysis showed PFTBA-SC composites were beneficial for microvascular growth, which provided sustained oxygen for regenerating nerve in the later stages of nerve regeneration. In conclusion, enhanced survival of SCs by PFTBA is capable of promoting sciatic nerve regeneration and functional recovery, which provides a new avenue for achieving better functional recovery in the treatment of peripheral nerve injuries. Copyright © 2016 John Wiley & Sons, Ltd.
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, PR China.
Teng
T
Ma
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, PR China.
Lei
L
Zhu
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, PR China.
Yafeng
Y
Yang
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, PR China.
Xin
X
Quan
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, PR China.
Liangliang
L
Huang
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, PR China.
Zhongyang
Z
Liu
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, PR China.
Zhen
Z
Sun
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, PR China.
Shu
S
Zhu
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, PR China.
Jinghui
J
Huang
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, PR China.
Zhuojing
Z
Luo
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D005466:Fluorocarbons / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000254:growth & development; D009416:Nerve Regeneration / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology*
D005466:Fluorocarbons; D049452:Green Fluorescent Proteins; C008807:perfluorotributylamine; D010100:Oxygen
Hypoxia; Nerve regeneration; Oxygenation; Perfluorocarbon; Perfluorotributylamine; Peripheral nerve injury; Schwann cells; Survival