柳小军,申火云,高红霞,管文超,许琳琳,李贵才.取向性PCL-SF/DFO复合支架的制备及用于周围神经再生的研究[J].表面技术,2024,53(23):97-110.
LIU Xiaojun,SHEN Huoyun,GAO Hongxia,GUAN Wenchao,XU Linlin,LI Guicai.Preparation of Oriented PCL-SF/DFO Composite Scaffold for Peripheral Nerve Regeneration[J].Surface Technology,2024,53(23):97-110 |
| 取向性PCL-SF/DFO复合支架的制备及用于周围神经再生的研究 |
| Preparation of Oriented PCL-SF/DFO Composite Scaffold for Peripheral Nerve Regeneration |
| 投稿时间：2024-08-09 修订日期：2024-10-14 |
| DOI：10.16490/j.cnki.issn.1001-3660.2024.23.008 |
| 中文关键词: 周围神经再生 静电纺丝 DFO 血管化 各向异性拓扑结构 |
| 英文关键词:peripheral nerve regeneration electrospinning DFO vascularization anisotropic topology |
| 基金项目:国家自然科学基金(32171352);国家药监局医用生物防护及植入器械质量评价重点实验室开放课题(2023-02) |
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| Author | Institution |
| LIU Xiaojun | Henan Institute for Drug and Medical Device Inspection, Zhengzhou 450018, China;NMPA Key Laboratory for Quality Evaluation of Medical Protective and Implant Devices, Zhengzhou 450018, China |
| SHEN Huoyun | Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China |
| GAO Hongxia | Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China |
| GUAN Wenchao | Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China |
| XU Linlin | Henan Institute for Drug and Medical Device Inspection, Zhengzhou 450018, China;NMPA Key Laboratory for Quality Evaluation of Medical Protective and Implant Devices, Zhengzhou 450018, China |
| LI Guicai | Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China |
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| 中文摘要: |
| 目的 制备具有各向异性拓扑结构的聚己内酯(PCL)-丝素蛋白(SF)/去铁胺(DFO)复合功能支架，定向诱导神经再生。方法 首先通过静电纺丝技术制备各向异性PCL-SF支架，然后通过多巴胺(DA)对复合支架进行修饰，并接枝DFO形成PCL-SF/DFO功能化复合支架。对支架进行一系列表征和成分分析，之后通过MTT探讨支架的细胞毒性。培养施万细胞(SCs)和内皮细胞(ECs)验证细胞活力，并进行免疫荧光染色，研究SCs和ECs在支架上的行为。最后通过RT-qPCR试验探讨相关的分子机制。结果 力学性能和亲水性测试表明，复合支架的杨氏模量和亲水性得到提升。通过生物学评价发现，支架可协同各向异性拓扑性结构和DFO，促进SCs和ECs的增殖，有效引导细胞定向生长。最后RT-qPCR表明，该功能化复合支架可使神经再生的相关基因YAP、Cntn2和促进血管化的关键基因VEGF的mRNA表达水平上调。结论 该支架可通过各向异性拓扑结构对SCs和ECs细胞的增殖及定向生长的行为进行调控，同时协同DFO促进神经损伤处血管化，从而加速周围神经再生。 |
| 英文摘要: |
| Excellent repair and functional reconstruction after peripheral nerve injury is a worldwide challenge. In severe cases, the injury can lead to complete nerve severance, impairing the continuity of nerve structure and function, which requires surgical treatment. Depending on the severity of the injury, patients may also require multiple surgeries and long rehabilitation, which greatly affects the life quality of the patients and brings a heavy economic burden and pressure to the patients and the healthcare system. Various artificial nerve scaffolds have been developed to repair PNI, but there are still many difficulties and shortcomings, such as the injured nerves can not be accurately oriented to the growth of the nerve, and the single-function scaffolds have a long-term continuous induction of the nerve. In addition, injured nerves cannot be precisely directed to grow, and single-function scaffolds are ineffective in inducing rapid nerve repair over a long period of time. In this study, polycaprolactone (PCL)-silk fibroin (SF)/desferrioxamine (DFO) composite functional scaffolds with anisotropic topology were prepared, which could promote nerve regeneration by directional inducing of nerve regeneration and realize long-term stable release of DFO, providing a new strategy for repairing peripheral nerve injury. Anisotropic PCL-SF composite scaffolds were firstly prepared by electrostatic spinning technique, and then the composite scaffolds were modified by dopamine (DA) and grafted with DFO to form PCL-SF/DFO functionalized composite scaffolds. The physicochemical properties of the scaffolds were characterized by light microscopy, scanning electron microscopy (SEM), hydrophilicity test, mechanical properties, degradation, etc. Fourier infrared (FTIR) analysis, and drug release assay of DFO were conducted, and then the cytotoxicity of the scaffolds was investigated by MTT, and the cellular viability of the scaffolds was verified by culturing Schwann cells (SCs) and endothelial cells (ECs). The viability and immunofluorescence staining of cell morphology were used to study the behavior of SCs and ECs on the scaffolds, and finally RT-qPCR was used to explore the relevant molecular mechanisms. The results showed that PCL-SF/DFO composite functional scaffolds with biomimetic anisotropic topology were prepared by electrospinning method. Mechanical properties and hydrophilicity tests showed that the DA-modified PCL-SF scaffolds with anisotropic topology had greater Young's modulus and better wettability than the DA-modified disordered PCL-SF nanofibers without DA modification. MTT experiments demonstrated that the PCL-SF scaffolds added with different concentrations of DFO were free from cytotoxicity; The scaffolds were found to synergize anisotropic topology structure with DFO through biological evaluations. The biological evaluation showed that the scaffolds could synergize the anisotropic topology with DFO to promote the proliferation of SCs and ECs and effectively guide the directed cell growth. Finally, RT-qPCR showed that the mRNA expression levels of the genes related to the promotion of neural regeneration, YAP, and Cntn2, as well as the gene related to the promotion of vascularization, VEGF, were up-regulated. In summary, PCL-SF/DFO composite functional scaffolds with anisotropic topology were successfully prepared, which can regulate the proliferation and directional growth behaviors of SCs and ECs through anisotropic topology, and at the same time, synergistically with DFO can promote vascularization of nerve injuries, thus accelerating peripheral nerve regeneration, which provides important reference for constructing artificial nerve implants for peripheral nerve regeneration. |
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