Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China; Military Medical Innovation Center, The Fourth Military Medical University, Xi'an, 710032, China; Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, 710032, China.
Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Biomaterials. 2022 Oct;289:121755. doi: 10.1016/j.biomaterials.2022.121755. Epub 2022 Aug 22.
Local hypoxia in cellular grafts remains a challenge during the repair of peripheral nerve injury. Oxygen carriers (perfluorotributylamine, PFTBA) have been shown to provide oxygen to Schwann cells (SCs) for a short period. However, the limited oxygen supply from oxygen-carrying materials hinders the ability of such systems to counteract hypoxia over an extended period and limits their therapeutic potential. In this study, PFTBA/VEGF core-shell fibers were fabricated through coaxial electrospinning to construct an oxygen supply system that can sequentially provide oxygen, first via the oxygen carrier and subsequently by promoting angiogenesis via VEGF. Then, the oxygen release and proangiogenic effects of the PFTBA/VEGF core-shell fibers were examined in vitro. Furthermore, sequential oxygen supply conduits prepared using the fibers and filled with SCs were used to bridge 15-mm-long sciatic nerve defects in rats. The PFTBA-VEGF system was confirmed to protect SCs from hypoxia and promote angiogenesis in vitro. Subsequent in vivo studies showed that after the oxygen carried by PFTBA was exhausted, the VEGF could induce neovascularization, and the nascent blood vessels acted as sequential oxygen suppliers for SCs during nerve regeneration. In addition, rats transplanted with the sequential oxygen supply system showed significant morphological and functional improvements in axonal regeneration, the sciatic function index, and the muscle wet weight ratio. The final functional outcomes were similar after treatment with the sequential oxygen supply conduits and autografts. Western blots revealed that the VEGF in the system could upregulate p-AMPK, contributing to axon regeneration after sciatic nerve injury. The sequential oxygen supply system offers essential insights into the oxygen regulation of biomaterials and highlights the potential of oxygen supply strategies as therapeutic approaches for repairing defects in peripheral nerves and other aerobic tissues.
细胞移植物中的局部缺氧仍然是外周神经损伤修复过程中的一个挑战。氧载体（全氟三丁胺，PFTBA）已被证明可以在短时间内向施旺细胞（SCs）提供氧气。然而，氧载体材料提供的氧气有限，限制了这些系统在较长时间内对抗缺氧的能力，并限制了它们的治疗潜力。在这项研究中，通过同轴静电纺丝制备了 PFTBA/VEGF 核壳纤维，构建了一种可以依次提供氧气的供氧系统，首先通过氧载体提供氧气，随后通过 VEGF 促进血管生成。然后，体外研究了 PFTBA/VEGF 核壳纤维的氧气释放和促血管生成作用。此外，使用纤维制备并填充SCs 的顺序供氧导管被用于桥接大鼠 15mm 长的坐骨神经缺损。PFTBA-VEGF 系统被证实可以保护 SCs 免受缺氧，并促进体外血管生成。随后的体内研究表明，当 PFTBA 携带的氧气耗尽后，VEGF 可以诱导血管新生，新生血管在神经再生过程中充当SCs 的顺序供氧源。此外，移植了顺序供氧系统的大鼠在轴突再生、坐骨神经功能指数和肌肉湿重比方面表现出明显的形态和功能改善。用顺序供氧导管和自体移植物治疗后的最终功能结果相似。Western blot 分析显示，系统中的 VEGF 可以上调 p-AMPK，促进坐骨神经损伤后的轴突再生。该顺序供氧系统为生物材料的氧气调节提供了重要的见解，并强调了氧气供应策略作为修复外周神经和其他需氧组织缺陷的治疗方法的潜力。
