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载有人纤连蛋白/壳聚糖/神经生长因子神经导管复合 RGD-TA-PPY 水凝胶通过 PI3K/AKT 信号通路促进大鼠坐骨神经缺损的再生。

PLCL/SF/NGF nerve conduit loaded with RGD-TA-PPY hydrogel promotes regeneration of sciatic nerve defects in rats through PI3K/AKT signalling pathways.

机构信息

Department of Orthopedic, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of Orthopedic, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

J Cell Mol Med. 2024 Aug;28(15):e18544. doi: 10.1111/jcmm.18544.


DOI:10.1111/jcmm.18544
PMID:39098996
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11298313/
Abstract

Peripheral nerve defect are common clinical problem caused by trauma or other diseases, often leading to the loss of sensory and motor function in patients. Autologous nerve transplantation has been the gold standard for repairing peripheral nerve defects, but its clinical application is limited due to insufficient donor tissue. In recent years, the application of tissue engineering methods to synthesize nerve conduits for treating peripheral nerve defect has become a current research focus. This study introduces a novel approach for treating peripheral nerve defects using a tissue-engineered PLCL/SF/NGF@TA-PPy-RGD conduit. The conduit was fabricated by combining electrospun PLCL/SF with an NGF-loaded conductive TA-PPy-RGD gel. The gel, synthesized from RGD-modified tannic acid (TA) and polypyrrole (PPy), provides growth anchor points for nerve cells. In vitro results showed that this hybrid conduit could enhance PC12 cell proliferation, migration, and reduce apoptosis under oxidative stress. Furthermore, the conduit activated the PI3K/AKT signalling pathway in PC12 cells. In a rat model of sciatic nerve defect, the PLCL/SF/NGF@TA-PPy-RGD conduit significantly improved motor function, gastrocnemius muscle function, and myelin sheath axon thickness, comparable to autologous nerve transplantation. It also promoted angiogenesis around the nerve defect. This study suggests that PLCL/SF/NGF@TA-PPy-RGD conduits provide a conducive environment for nerve regeneration, offering a new strategy for peripheral nerve defect treatment, this study provided theoretical basis and new strategies for the research and treatment of peripheral nerve defect.

摘要

周围神经缺损是由创伤或其他疾病引起的常见临床问题,常导致患者感觉和运动功能丧失。自体神经移植一直是修复周围神经缺损的金标准,但由于供体组织不足,其临床应用受到限制。近年来,应用组织工程方法合成神经导管治疗周围神经缺损已成为当前研究热点。本研究采用组织工程化的 PLCL/SF/NGF@TA-PPy-RGD 导管治疗周围神经缺损。该导管通过将静电纺丝的 PLCL/SF 与负载 NGF 的导电 TA-PPy-RGD 凝胶结合而制成。该凝胶由 RGD 修饰的单宁酸 (TA) 和聚吡咯 (PPy) 合成,为神经细胞提供生长锚点。体外结果表明,这种杂化导管可以在氧化应激下增强 PC12 细胞的增殖、迁移,并减少细胞凋亡。此外,该导管还能激活 PC12 细胞中的 PI3K/AKT 信号通路。在大鼠坐骨神经缺损模型中,PLCL/SF/NGF@TA-PPy-RGD 导管显著改善了运动功能、比目鱼肌功能和髓鞘轴突厚度,与自体神经移植相当。它还促进了神经缺损周围的血管生成。本研究表明,PLCL/SF/NGF@TA-PPy-RGD 导管为神经再生提供了有利的环境,为周围神经缺损的治疗提供了新的策略,为周围神经缺损的研究和治疗提供了理论依据和新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/06a68c879b6d/JCMM-28-e18544-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/b4ae9459e929/JCMM-28-e18544-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/4509a0f35d9f/JCMM-28-e18544-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/94e64ee87036/JCMM-28-e18544-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/d5bee530cf28/JCMM-28-e18544-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/b55c5ebd2bc8/JCMM-28-e18544-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/8b8175764427/JCMM-28-e18544-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/1a8ebefb5ad4/JCMM-28-e18544-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/06a68c879b6d/JCMM-28-e18544-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/b4ae9459e929/JCMM-28-e18544-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/4509a0f35d9f/JCMM-28-e18544-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/94e64ee87036/JCMM-28-e18544-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/d5bee530cf28/JCMM-28-e18544-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/b55c5ebd2bc8/JCMM-28-e18544-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/8b8175764427/JCMM-28-e18544-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/1a8ebefb5ad4/JCMM-28-e18544-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ac/11298313/06a68c879b6d/JCMM-28-e18544-g007.jpg

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引用本文的文献

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[2]
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Pharmaceutics. 2024-12-8

本文引用的文献

[1]
Development of BDNF/NGF/IKVAV Peptide Modified and Gold Nanoparticle Conductive PCL/PLGA Nerve Guidance Conduit for Regeneration of the Rat Spinal Cord Injury.

Macromol Biosci. 2024-5

[2]
Effect of Electrical Stimulation on PC12 Cells Cultured in Different Hydrogels: Basis for the Development of Biomaterials in Peripheral Nerve Tissue Engineering.

Pharmaceutics. 2023-12-12

[3]
Bioactive-Loaded Hydrogels Based on Bacterial Nanocellulose, Chitosan, and Poloxamer for Rebalancing Vaginal Microbiota.

Pharmaceuticals (Basel). 2023-11-30

[4]
Improved Physiochemical Properties of Chitosan@PCL Nerve Conduits by Natural Molecule Crosslinking.

Biomolecules. 2023-11-27

[5]
An injectable and adaptable hydrogen sulfide delivery system for modulating neuroregenerative microenvironment.

Sci Adv. 2023-12-22

[6]
Growth factors: Bioactive macromolecular drugs for peripheral nerve injury treatment - Molecular mechanisms and delivery platforms.

Biomed Pharmacother. 2024-1

[7]
The role of preoperative ultrasound in the management of peripheral nerve injuries.

Clin Neurol Neurosurg. 2024-1

[8]
Enhancement of nerve regeneration through schwann cell-mediated healing in a 3D printed polyacrylonitrile conduit incorporating hydrogel and graphene quantum dots: a study on rat sciatic nerve injury model.

Biomed Mater. 2023-12-21

[9]
Genome-wide study reveals novel roles for formin-2 in axon regeneration as a microtubule dynamics regulator and therapeutic target for nerve repair.

Neuron. 2023-12-20

[10]
Chitosan-Based Conduits with Different Inner Diameters at both Ends Combined with Modified Formula Radix Hedysari Promote Nerve Transposition Repair.

Front Biosci (Landmark Ed). 2023-11-24

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