Sustained Release of Vascular Endothelial Growth Factor A and Basic Fibroblast Growth Factor from Nanofiber Membranes Reduces Oxygen/glucose Deprivation-induced Injury to Neurovascular Units

Overview

Journal Neural Regen Res

Date 2023 Oct 16

PMID 37843225

Authors

Yifang Wu

Jun Sun

Qi Lin

Dapeng Wang

Jian Hai

Affiliations

Soon will be listed here.

Abstract

Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor (VEGFA/bFGF) expression in the penumbra of cerebral ischemia can increase vascular volume, reduce lesion volume, and enhance neural cell proliferation and differentiation, thereby exerting neuroprotective effects. However, the beneficial effects of endogenous VEGFA/bFGF are limited as their expression is only transiently increased. In this study, we generated multilayered nanofiber membranes loaded with VEGFA/bFGF using layer-by-layer self-assembly and electrospinning techniques. We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month. This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation, inhibited neuronal apoptosis, upregulated the expression of tight junction proteins, and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation. Furthermore, this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3 (JAK2/STAT3), Bax/Bcl-2, and cleaved caspase-3. Therefore, this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.

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References

Sayad A, Uddin S, Yao S, Wilson H, Chan J, Zhao H . A magnetoimpedance biosensor microfluidic platform for detection of glial fibrillary acidic protein in blood for acute stroke classification. Biosens Bioelectron. 2022; 211:114410. DOI: 10.1016/j.bios.2022.114410. View

Lu L, Armstrong E, Yager J, Unsworth L . Sustained Release of Dexamethasone from Sulfobutyl Ether β-cyclodextrin Modified Self-Assembling Peptide Nanoscaffolds in a Perinatal Rat Model of Hypoxia-Ischemia. Adv Healthc Mater. 2019; 8(11):e1900083. DOI: 10.1002/adhm.201900083. View

Liu Y, Long L, Zhang F, Hu X, Zhang J, Hu C . Microneedle-mediated vascular endothelial growth factor delivery promotes angiogenesis and functional recovery after stroke. J Control Release. 2021; 338:610-622. DOI: 10.1016/j.jconrel.2021.08.057. View

Ben-Zvi A, Liebner S . Developmental regulation of barrier- and non-barrier blood vessels in the CNS. J Intern Med. 2021; 292(1):31-46. DOI: 10.1111/joim.13263. View

Liu X, Yang M, Lei F, Wang Y, Yang M, Mao C . Highly Effective Stroke Therapy Enabled by Genetically Engineered Viral Nanofibers. Adv Mater. 2022; 34(20):e2201210. DOI: 10.1002/adma.202201210. View

Zhang K, Tu M, Gao W, Cai X, Song F, Chen Z . Hollow Prussian Blue Nanozymes Drive Neuroprotection against Ischemic Stroke via Attenuating Oxidative Stress, Counteracting Inflammation, and Suppressing Cell Apoptosis. Nano Lett. 2019; 19(5):2812-2823. DOI: 10.1021/acs.nanolett.8b04729. View

Wu S, Dong T, Li Y, Sun M, Qi Y, Liu J . State-of-the-art review of advanced electrospun nanofiber yarn-based textiles for biomedical applications. Appl Mater Today. 2022; 27:101473. PMC: 8994858. DOI: 10.1016/j.apmt.2022.101473. View

Subramanian A, Krishnan U, Sethuraman S . Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration. J Biomed Sci. 2009; 16:108. PMC: 2790452. DOI: 10.1186/1423-0127-16-108. View

Huang Z, Qian K, Chen J, Qi Y, E Y, Liang J . A biomimetic zeolite-based nanoenzyme contributes to neuroprotection in the neurovascular unit after ischaemic stroke via efficient removal of zinc and ROS. Acta Biomater. 2022; 144:142-156. DOI: 10.1016/j.actbio.2022.03.018. View

10.

Zhu H, Jian Z, Zhong Y, Ye Y, Zhang Y, Hu X . Janus Kinase Inhibition Ameliorates Ischemic Stroke Injury and Neuroinflammation Through Reducing NLRP3 Inflammasome Activation JAK2/STAT3 Pathway Inhibition. Front Immunol. 2021; 12:714943. PMC: 8339584. DOI: 10.3389/fimmu.2021.714943. View

11.

Yang C, Lavayen B, Liu L, Sanz B, DeMars K, Larochelle J . Neurovascular protection by adropin in experimental ischemic stroke through an endothelial nitric oxide synthase-dependent mechanism. Redox Biol. 2021; 48():102197. PMC: 8633041. DOI: 10.1016/j.redox.2021.102197. View

12.

Chow B, Nunez V, Kaplan L, Granger A, Bistrong K, Zucker H . Caveolae in CNS arterioles mediate neurovascular coupling. Nature. 2020; 579(7797):106-110. PMC: 7060132. DOI: 10.1038/s41586-020-2026-1. View

13.

Keogh C, Yu S, Wei L . The effect of recombinant human erythropoietin on neurovasculature repair after focal ischemic stroke in neonatal rats. J Pharmacol Exp Ther. 2007; 322(2):521-8. DOI: 10.1124/jpet.107.121392. View

14.

Ghori A, Prinz V, Nieminen-Kehla M, Bayerl S, Kremenetskaia I, Riecke J . Vascular Endothelial Growth Factor Augments the Tolerance Towards Cerebral Stroke by Enhancing Neurovascular Repair Mechanism. Transl Stroke Res. 2022; 13(5):774-791. PMC: 9391249. DOI: 10.1007/s12975-022-00991-z. View

15.

Bordoni M, Scarian E, Rey F, Gagliardi S, Carelli S, Pansarasa O . Biomaterials in Neurodegenerative Disorders: A Promising Therapeutic Approach. Int J Mol Sci. 2020; 21(9). PMC: 7247337. DOI: 10.3390/ijms21093243. View

16.

Jin L, Zhu Z, Hong L, Qian Z, Wang F, Mao Z . ROS-responsive 18β-glycyrrhetic acid-conjugated polymeric nanoparticles mediate neuroprotection in ischemic stroke through HMGB1 inhibition and microglia polarization regulation. Bioact Mater. 2022; 19:38-49. PMC: 8980441. DOI: 10.1016/j.bioactmat.2022.03.040. View

17.

Wang H, Ran H, Yin Y, Xu X, Jiang B, Yu S . Catalpol improves impaired neurovascular unit in ischemic stroke rats via enhancing VEGF-PI3K/AKT and VEGF-MEK1/2/ERK1/2 signaling. Acta Pharmacol Sin. 2021; 43(7):1670-1685. PMC: 9253350. DOI: 10.1038/s41401-021-00803-4. View

18.

Han F, Zhang P, Chen T, Lin C, Wen X, Zhao P . A LbL-Assembled Bioactive Coating Modified Nanofibrous Membrane for Rapid Tendon-Bone Healing in ACL Reconstruction. Int J Nanomedicine. 2019; 14:9159-9172. PMC: 6883935. DOI: 10.2147/IJN.S214359. View

19.

Liu M, Wu Y, Liu Y, Chen Z, He S, Zhang H . Basic Fibroblast Growth Factor Protects Astrocytes Against Ischemia/Reperfusion Injury by Upregulating the Caveolin-1/VEGF Signaling Pathway. J Mol Neurosci. 2018; 64(2):211-223. DOI: 10.1007/s12031-017-1023-9. View

20.

Wang D, Jin K, Zhao P, Lin Q, Kang K, Hai J . Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen-Glucose Deprivation-Induced Ischemic Neuronal Injury. Int J Nanomedicine. 2021; 16:3661-3678. PMC: 8168836. DOI: 10.2147/IJN.S307335. View