Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Research and Development Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.
Theranostics. 2020 Jul 11;10(20):8957-8973. doi: 10.7150/thno.45035. eCollection 2020.
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. 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 . The system was used to bridge large sciatic nerve defects in rats. PFTBA core-shell fibers provided high levels of oxygen to SCs , enhancing their survival, and increasing NGF, BDNF, and VEGF expression in 2D and 3D culture systems under hypoxic condition. 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. 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.
局部缺氧是细胞移植物制备和周围神经损伤治疗的一个挑战。在我们之前的研究中,我们证明了全氟三丁胺(PFTBA)可以为施万细胞(SCs)提供短期的氧气供应,并在神经损伤的早期阶段对抗缺氧对SCs 的有害影响。然而,PFTBA 中氧气的快速释放使其无法在较长时间内对抗缺氧,从而限制了其在周围神经损伤中的性能。在这项研究中,通过同轴静电纺丝制备了基于 PFTBA 的氧载体系统,以延长氧气释放的时间过程。制备、优化了核壳结构,并评估了富含 PFTBA 的核壳纤维的氧动力学。在 2D 和 3D 系统以及体内,研究了核壳结构对SCs 存活和功能的影响。该系统用于桥接大鼠大坐骨神经缺损。PFTBA 核壳纤维为SCs 提供了高水平的氧气,增强了它们的存活,并在缺氧条件下增加了 2D 和 3D 培养系统中神经生长因子(NGF)、脑源性神经营养因子(BDNF)和血管内皮生长因子(VEGF)的表达。免疫荧光分析表明,在植入后 14 天,大多数在 PFTBA 导管中表达 GFP 的SCs 仍然存活。我们发现,PFTBA 氧载体支架中的轴突改善了轴突再生、髓鞘形成和恢复。通过同轴静电纺丝技术制备了一种核壳纤维中的合成氧载体,通过延长氧气供应,能够增强SCs 的存活和神经再生。这些发现为制造细胞支架提供了一种新策略,以实现周围神经损伤治疗和其他需氧组织损伤中的再生。