Establishment of FK506-Enriched PLGA Nanomaterial Neural Conduit Produced by Electrospinning for the Repair of Long- Distance Peripheral Nerve Injury
Establishment of FK506-Enriched PLGA Nanomaterial Neural Conduit Produced by Electrospinning for the Repair of Long- Distance Peripheral Nerve Injury
复制标题
静电纺丝富集FK506 PLGA纳米材料神经导管的建立用于远距离周围神经损伤的修复
DOI：
10.1155/2022/3530620
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发表时间：
2022
影响因子：
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通讯作者：
Jian-Jun Li
中科院分区：
文献类型：
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作者：
Ting-Min Xu;Hong-Yu Chu;Ming Li;Zuliyaer Talifu;Han Ke;Yun-Zhu Pan;Xin Xu;Yan-hua Wang;Wei Guo;Chuan-Lin Wang;Feng Gao;Jian-Jun Li
周围神经损伤（PNI）是一种严重的创伤并发症。自体神经移植是治疗长距离周围神经缺损的金标准，但常常受到供体部位不足、术后疼痛和供体部位感觉异常的限制。周围神经组织工程导致神经导管的发展以取代自体神经移植物。本研究旨在评估一种富含 FDA 批准的免疫抑制剂他克莫司 (FK506) 的新型电纺纳米材料神经导管，用于修复远距离周围神经损伤。以FK506为原料，采用静电纺丝法制备聚乳酸-乙醇酸(PLGA)纳米纤维膜，并卷制成内径1mm、长度15mm的空心圆柱形神经血管。在体外进行材料表征、机械测试、降解、药物释放、细胞毒性、细胞增殖和迁移测定。使用电纺神经导管桥接在体内修复大鼠长距离坐骨神经损伤，并通过步态分析、电生理学和神经肌肉组织学评估神经再生以及肌肉和运动功能恢复。与PLGA相比，PLGA/FK506纳米材料神经导管在形态、力学性能和化学结构上几乎没有变化。在体外，PLGA/FK506表现出较低的细胞毒性和较好的生物相容性，有效促进雪旺细胞的增殖、粘附和迁移。在体内，PLGA/FK506对移植后12周的坐骨神经指数、复合肌肉动作电位强度和延迟时间、神经再生质量有较好的影响，有效促进大鼠远距离缺损坐骨神经再生和功能恢复。富集FK506的PLGA纳米材料神经导管为修复远距离周围神经损伤提供了有效方法，具有潜在的临床应用前景。
Peripheral nerve injury (PNI) is a serious complication of trauma. Autologous nerve transplantation is the gold standard for the treatment of long-distance peripheral nerve defects, but is often limited by insufficient donor sites, postoperative pain, and paresthesia at the donor site. Peripheral nerve tissue engineering has led to the development of neural conduits to replace autologous nerve grafts. This study aimed to evaluate a new type of electrospun nanomaterial neural conduit, enriched with tacrolimus (FK506), which is an FDA-approved immunosuppressant, for the repair of long-distance peripheral nerve injuries. Poly (lactic-co-glycolic acid) (PLGA) nanofibrous films, with FK506, were prepared by electrostatic spinning and rolled into hollow cylindrical nerve vessels with an inner diameter of 1mm and length of 15 mm. Material characterization, mechanical testing, degradation, drug release, cytotoxicity, cell proliferation, and migration assays were performed in vitro. Long-distance sciatic nerve injuries in rats were repaired in vivo using electrospun nerve conduit bridging, and nerve regeneration and muscle and motor function recovery were evaluated by gait analysis, electrophysiology, and neuromuscular histology. Compared to PLGA, the PLGA/FK506 nanomaterial neural conduit showed little change in morphology, mechanical properties, and chemical structure. In vitro, PLGA/FK506 showed lower cytotoxicity and better biocompatibility and effectively promoted the proliferation, adhesion, and migration of Schwann cells. In vivo, PLGA/FK506 had a better effect on sciatic nerve index, compound muscle action potential intensity and delay time, and nerve regeneration quality 12 weeks post-transplantation, effectively promoting long-distance defect sciatic nerve regeneration and functional recovery in rats. FK506-enriched PLGA nanomaterial neural conduits offer an effective method for repairing long-distance peripheral nerve injury and have potential clinical applications.