Theranostics 2020; 10(20):8957-8973. doi:10.7150/thno.45035

Research Paper

Oxygen carrier in core-shell fibers synthesized by coaxial electrospinning enhances Schwann cell survival and nerve regeneration

Teng Ma1,2,3*, Yafeng Yang4*, Xin Quan5*, Lei Lu6, Bing Xia1, Jianbo Gao1, Fengyu Qi7, Shengyou Li1, Laihe Zhao1, Liangwei Mei1, Yi Zheng1, Yanbing Shen3, Zhuojing Luo1✉, Yan Jin2✉, Jinghui Huang1✉

1. Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
2. Research and Development Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.
3. Hospital of 76th Group Army of PLA, Xining, 810000, China.
4. Department of Orthopedics, Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100048, China.
5. Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
6. Department of Oral Anatomy and Physiology, State Key Laboratory of Military Stomatology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
7. Department of Orthopedics, General Hospital of Central Theater Command of PLA, Wuhan, 430070, China.
*These authors contributed equally to this work.

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Citation:
Ma T, Yang Y, Quan X, Lu L, Xia B, Gao J, Qi F, Li S, Zhao L, Mei L, Zheng Y, Shen Y, Luo Z, Jin Y, Huang J. Oxygen carrier in core-shell fibers synthesized by coaxial electrospinning enhances Schwann cell survival and nerve regeneration. Theranostics 2020; 10(20):8957-8973. doi:10.7150/thno.45035. Available from https://www.thno.org/v10p8957.htm

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Abstract

Rationale: Local hypoxia is a challenge for fabrication of cellular grafts and treatment of peripheral nerve injury. In our previous studies, we demonstrated that perfluorotributylamine (PFTBA) could provide short term oxygen supply to Schwann cells (SCs) and counteract the detrimental effects of hypoxia on SCs during the early stages of nerve injury. However, the quick release of oxygen in PFTBA compromised its ability to counteract hypoxia over an extended time, limiting its performance in peripheral nerve injury.

Methods: In this study, PFTBA-based oxygen carrier systems were prepared through coaxial electrospinning to prolong the time course of oxygen release. Core-shell structures were fabricated, optimized, and the oxygen kinetics of PFTBA-enriched core-shell fibers evaluated. The effect of core-shells on the survival and function of SCs was examined in both 2D and 3D systems as well as in vivo. The system was used to bridge large sciatic nerve defects in rats.

Results: PFTBA core-shell fibers provided high levels of oxygen to SCs in vitro, enhancing their survival, and increasing NGF, BDNF, and VEGF expression in 2D and 3D culture systems under hypoxic condition. In vivo analysis showed that the majority of GFP-expressing SCs in the PFTBA conduit remained viable 14 days post-implantation. We found that axons in PFTBA oxygen carrier scaffold improved axonal regeneration, remyelination, and recovery.

Conclusion: A synthetic oxygen carrier in core-shell fibers was fabricated by the coaxial electrospinning technique and was capable of enhancing SC survival and nerve regeneration by prolonged oxygen supply. These findings provide a new strategy for fabricating cellular scaffolds to achieve regeneration in peripheral nerve injury treatment and other aerobic tissue injuries.

Keywords: Perfluorotributylamine, Coaxial electrospinning, Peripheral nerve injury, Nerve regeneration, Hypoxia