| 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],53(23):97-110 |
| Preparation of Oriented PCL-SF/DFO Composite Scaffold for Peripheral Nerve Regeneration |
| Received:August 09, 2024 Revised:October 14, 2024 |
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| DOI：10.16490/j.cnki.issn.1001-3660.2024.23.008 |
| KeyWord:peripheral nerve regeneration electrospinning DFO vascularization anisotropic topology |
| Author | Institution |
| LIU Xiaojun |
Henan Institute for Drug and Medical Device Inspection, Zhengzhou , China;NMPA Key Laboratory for Quality Evaluation of Medical Protective and Implant Devices, Zhengzhou , China |
| SHEN Huoyun |
Key Laboratory of Neuroregeneration, Nantong University, Nantong , China |
| GAO Hongxia |
Key Laboratory of Neuroregeneration, Nantong University, Nantong , China |
| GUAN Wenchao |
Key Laboratory of Neuroregeneration, Nantong University, Nantong , China |
| XU Linlin |
Henan Institute for Drug and Medical Device Inspection, Zhengzhou , China;NMPA Key Laboratory for Quality Evaluation of Medical Protective and Implant Devices, Zhengzhou , China |
| LI Guicai |
Key Laboratory of Neuroregeneration, Nantong University, Nantong , China |
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| Abstract: |
| 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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