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外泌体负载的导电水凝胶通过免疫调节和增强髓鞘轴突生长协同促进脊髓损伤后的组织修复。

Exosomes-Loaded Electroconductive Hydrogel Synergistically Promotes Tissue Repair after Spinal Cord Injury via Immunoregulation and Enhancement of Myelinated Axon Growth.

机构信息

School of Materials Science and Engineering and National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, No. 381, Wushan Road, Tianhe District, Guangzhou, 510641, China.

Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

出版信息

Adv Sci (Weinh). 2022 May;9(13):e2105586. doi: 10.1002/advs.202105586. Epub 2022 Mar 6.

DOI:10.1002/advs.202105586
PMID:35253394
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9069372/
Abstract

Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell-derived exosomes (BMSC-exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue-like electroconductive hydrogels loaded with BMSC-exosomes are developed for the synergistic treatment of SCI. These exosomes-loaded electroconductive hydrogels modulate microglial M2 polarization via the NF-κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68-positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC-exosomes is a promising therapeutic strategy for SCI repair.

摘要

导电水凝胶是加速脊髓损伤 (SCI) 修复的极具吸引力的候选物，因为它们与神经组织的电学和机械性能相匹配。然而，导电水凝胶的植入可能会加重炎症，并阻碍其修复效果。骨髓间充质干细胞衍生的外泌体 (BMSC-exosomes) 具有免疫调节和组织再生作用，因此，开发了具有神经组织样导电性的水凝胶负载 BMSC-exosomes 以协同治疗 SCI。这些负载外泌体的导电水凝胶通过 NF-κB 通路调节小胶质细胞 M2 极化，并协同增强神经干细胞 (NSCs) 的神经元和少突胶质细胞分化，同时抑制星形胶质细胞分化，还通过 PTEN/PI3K/AKT/mTOR 通路促进轴突生长。此外，外泌体复合导电水凝胶可显著减少 CD68 阳性小胶质细胞的数量，增强局部 NSCs 的募集，并促进神经元和轴突的再生，从而在 SCI 小鼠模型的早期阶段实现显著的功能恢复。因此，本研究结果表明，导电水凝胶和 BMSC-exosomes 的联合应用是 SCI 修复的一种有前途的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/6c5527f4c0f1/ADVS-9-2105586-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/33cb604946ed/ADVS-9-2105586-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/474cdc16cf49/ADVS-9-2105586-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/af66df56697b/ADVS-9-2105586-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/00ca813bd890/ADVS-9-2105586-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/e507ef66eb54/ADVS-9-2105586-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/7800a8b03895/ADVS-9-2105586-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/768ab5be4cf9/ADVS-9-2105586-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/f41ddc4f602a/ADVS-9-2105586-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/6c5527f4c0f1/ADVS-9-2105586-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/33cb604946ed/ADVS-9-2105586-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/474cdc16cf49/ADVS-9-2105586-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/af66df56697b/ADVS-9-2105586-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/00ca813bd890/ADVS-9-2105586-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/e507ef66eb54/ADVS-9-2105586-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/7800a8b03895/ADVS-9-2105586-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/768ab5be4cf9/ADVS-9-2105586-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/f41ddc4f602a/ADVS-9-2105586-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ed/9069372/6c5527f4c0f1/ADVS-9-2105586-g007.jpg

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引用本文的文献

[1]
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Int J Nanomedicine. 2025-8-27

[2]
Mesenchymal stem cells in treating human diseases: molecular mechanisms and clinical studies.

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[3]
Exosome-Loaded Bioscaffolds for Spinal Cord Injuries: A Review.

Stem Cells Int. 2025-7-30

[4]
Iridoids derived from Valeriana jatamansi Jones alleviates neuroinflammation and blood spinal cord barrier permeability after spinal cord injury by activating the Nrf2/HO-1 signaling pathway.

Front Pharmacol. 2025-7-18

[5]
Exosomes Derived from Tanshinone IIA-Pretreated Umbilical Cord Mesenchymal Stem Cells Repair Traumatic Spinal Cord Injury by miR-223-5p/USP8/NLRP3 Axis.

ACS Appl Mater Interfaces. 2025-8-13

[6]
Nanomedicine-Based Ophthalmic Drug Delivery Systems for the Treatment of Ocular Diseases.

Int J Nanomedicine. 2025-7-21

[7]
Extracellular Vesicle Metabolomics Holds Promise for Adult Axon Regeneration.

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[8]
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Front Bioeng Biotechnol. 2025-7-9

[9]
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Mater Today Bio. 2025-6-14

[10]
Role of MS4A7 in Regulating Microglial Polarization and Neuroinflammation in Spinal Cord Injury via the cGAS-STING-NLRP3 Axis.

CNS Neurosci Ther. 2025-6

本文引用的文献

[1]
Extracellular Matrix-Based Conductive Interpenetrating Network Hydrogels with Enhanced Neurovascular Regeneration Properties for Diabetic Wounds Repair.

Adv Healthc Mater. 2022-1

[2]
An injectable, self-healing, electroconductive extracellular matrix-based hydrogel for enhancing tissue repair after traumatic spinal cord injury.

Bioact Mater. 2021-6-1

[3]
3D bioprinting of conductive hydrogel for enhanced myogenic differentiation.

Regen Biomater. 2021-8-14

[4]
Enhanced Electroactivity, Mechanical Properties, and Printability through the Addition of Graphene Oxide to Photo-Cross-linkable Gelatin Methacryloyl Hydrogel.

ACS Biomater Sci Eng. 2021-6-14

[5]
Mesenchymal stem cell-derived exosomes containing miR-145-5p reduce inflammation in spinal cord injury by regulating the TLR4/NF-κB signaling pathway.

Cell Cycle. 2021-5

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Self-curling electroconductive nerve dressing for enhancing peripheral nerve regeneration in diabetic rats.

Bioact Mater. 2021-4-14

[7]
MiR-17-92 enriched exosomes derived from multipotent mesenchymal stromal cells enhance axon-myelin remodeling and motor electrophysiological recovery after stroke.

J Cereb Blood Flow Metab. 2021-5

[8]
Transplantation of Human Mesenchymal Stem-Cell-Derived Exosomes Immobilized in an Adhesive Hydrogel for Effective Treatment of Spinal Cord Injury.

Nano Lett. 2020-6-10

[9]
Elastomeric conductive hybrid hydrogels with continuous conductive networks.

J Mater Chem B. 2019-3-8

[10]
Rapamycin inhibits B-cell activating factor (BAFF)-stimulated cell proliferation and survival by suppressing Ca-CaMKII-dependent PTEN/Akt-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells.

Cell Calcium. 2020-5

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