A 3D fiber-hydrogel based non-viral gene delivery platform reveals that microRNAs promote axon regeneration and enhance functional recovery following spinal cord injury

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...

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Main 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
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/150957
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spelling sg-ntu-dr.10356-1509572023-03-05T16:28:51Z A 3D fiber-hydrogel based non-viral gene delivery platform reveals that microRNAs promote axon regeneration and enhance functional recovery following spinal cord injury 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 School of Chemical and Biomedical Engineering Interdisciplinary Graduate School (IGS) Lee Kong Chian School of Medicine (LKCMedicine) Genome Institute of Singapore, A*STAR Science::Biological sciences::Cytology Engineering::Chemical engineering::Biochemical engineering Science::Biological sciences::Molecular biology Hydrogel RNA Interference Neural Tissue Engineering Electrospinning RNA Sequencing 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. Ministry of Education (MOE) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This work is supported by the National Research Foundation, Singapore, under its Intra-CREATE Thematic Grant Programme (NRF2019-THE002-0001) and NMRC-CBRG grant (NMRC/CBRG/0096/2015), as well as the MOE Tier 1 grants (RG38/19 and RG37/20). N.Z. and J.L. would like to acknowledge NTU by providing Nanyang Research Scholarship to carry out these research works. 2021-08-12T01:43:27Z 2021-08-12T01:43:27Z 2021 Journal Article 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-. https://dx.doi.org/10.1002/advs.202100805 2198-3844 https://hdl.handle.net/10356/150957 10.1002/advs.202100805 34050637 15 8 2100805 en NMRC/CBRG/0096/2015 RG38/19 NRF2019-THE002-0001 RG37/20 Advanced Science © 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. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences::Cytology
Engineering::Chemical engineering::Biochemical engineering
Science::Biological sciences::Molecular biology
Hydrogel
RNA Interference
Neural Tissue Engineering
Electrospinning
RNA Sequencing
spellingShingle Science::Biological sciences::Cytology
Engineering::Chemical engineering::Biochemical engineering
Science::Biological sciences::Molecular biology
Hydrogel
RNA Interference
Neural Tissue Engineering
Electrospinning
RNA Sequencing
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
A 3D fiber-hydrogel based non-viral gene delivery platform reveals that microRNAs promote axon regeneration and enhance functional recovery following spinal cord injury
description 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.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
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
format Article
author 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
author_sort Zhang, Na
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
title_short A 3D fiber-hydrogel based non-viral gene delivery platform reveals that microRNAs promote axon regeneration and enhance functional recovery following spinal cord injury
title_full A 3D fiber-hydrogel based non-viral gene delivery platform reveals that microRNAs promote axon regeneration and enhance functional recovery following spinal cord injury
title_fullStr A 3D fiber-hydrogel based non-viral gene delivery platform reveals that microRNAs promote axon regeneration and enhance functional recovery following spinal cord injury
title_full_unstemmed A 3D fiber-hydrogel based non-viral gene delivery platform reveals that microRNAs promote axon regeneration and enhance functional recovery following spinal cord injury
title_sort 3d fiber-hydrogel based non-viral gene delivery platform reveals that micrornas promote axon regeneration and enhance functional recovery following spinal cord injury
publishDate 2021
url https://hdl.handle.net/10356/150957
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