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Title: A 3D fiber-hydrogel based non-viral gene delivery platform reveals that microRNAs promote axon regeneration and enhance functional recovery following spinal cord injury
Authors: Zhang, Na
Lin, Junquan
Lin, Vincent Po Hen
Milbreta, Ulla
Chin, Jiah Shin
Chew, Elaine Guo Yan
Lian, Michelle Mulan
Foo, Jia Nee
Zhang, Kunyu
Wu, Wutian
Chew, Sing Yian
Keywords: Science::Biological sciences::Cytology
Engineering::Chemical engineering::Biochemical engineering
Science::Biological sciences::Molecular biology
Issue Date: 2021
Source: Zhang, N., Lin, J., Lin, V. P. H., Milbreta, U., Chin, J. S., Chew, E. G. Y., Lian, M. M., Foo, J. N., Zhang, K., Wu, W. & Chew, S. Y. (2021). A 3D fiber-hydrogel based non-viral gene delivery platform reveals that microRNAs promote axon regeneration and enhance functional recovery following spinal cord injury. Advanced Science, 8(15), 2100805-.
Project: NMRC/CBRG/0096/2015
Journal: Advanced Science 
Abstract: Current treatment approaches toward spinal cord injuries (SCI) have mainly focused on overcoming the inhibitory microenvironment that surrounds lesion sites. Unfortunately, the mere modulation of the cell/tissue microenvironment is often insufficient to achieve desired functional recovery. Therefore, stimulating the intrinsic growth ability of injured neurons becomes crucial. MicroRNAs (miRs) play significant roles during axon regeneration by regulating local protein synthesis at growth cones. However, one challenge of using miRs to treat SCI is the lack of efficient delivery approaches. Here, a 3D fiber-hydrogel scaffold is introduced which can be directly implanted into a spinal cord transected rat. This 3D scaffold consists of aligned electrospun fibers which provide topographical cues to direct axon regeneration, and collagen matrix which enables a sustained delivery of miRs. Correspondingly, treatment with Axon miRs (i.e., a cocktail of miR-132/miR-222/miR-431) significantly enhances axon regeneration. Moreover, administration of Axon miRs along with anti-inflammatory drug, methylprednisolone, synergistically enhances functional recovery. Additionally, this combined treatment also decreases the expression of pro-inflammatory genes and enhance gene expressions related to extracellular matrix deposition. Finally, increased Axon miRs dosage with methylprednisolone, significantly promotes functional recovery and remyelination. Altogether, scaffold-mediated Axon miR treatment with methylprednisolone is a promising therapeutic approach for SCI.
ISSN: 2198-3844
DOI: 10.1002/advs.202100805
Rights: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:IGS Journal Articles
LKCMedicine Journal Articles
SCBE Journal Articles

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