Delivery of Wnt inhibitor WIF1 via engineered polymeric microspheres promotes nerve regeneration after sciatic nerve crush

Injuries within the peripheral nervous system (PNS) lead to sensory and motor deficits, as well as neuropathic pain, which strongly impair the life quality of patients. Although most current PNS injury treatment approaches focus on using growth factors/small molecules to stimulate the regrowth of th...

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Main Authors: Zheng, Na, Lin, Junquan, Chin, Jiah Shin, Wiraja, Christian, Xu, Chenjie, McGrouther, Duncan Angus, Chew, Sing Yian
Other Authors: School of Chemical and Biomedical Engineering
Format: Journal Article
Language:English
Published: 2022
Subjects:
Online Access:https://hdl.handle.net/10356/156351
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author Zheng, Na
Lin, Junquan
Chin, Jiah Shin
Wiraja, Christian
Xu, Chenjie
McGrouther, Duncan Angus
Chew, Sing Yian
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Zheng, Na
Lin, Junquan
Chin, Jiah Shin
Wiraja, Christian
Xu, Chenjie
McGrouther, Duncan Angus
Chew, Sing Yian
author_sort Zheng, Na
collection NTU
description Injuries within the peripheral nervous system (PNS) lead to sensory and motor deficits, as well as neuropathic pain, which strongly impair the life quality of patients. Although most current PNS injury treatment approaches focus on using growth factors/small molecules to stimulate the regrowth of the injured nerves, these methods neglect another important factor that strongly hinders axon regeneration - the presence of axonal inhibitory molecules. Therefore, this work sought to explore the potential of pathway inhibition in promoting sciatic nerve regeneration. Additionally, the therapeutic window for using pathway inhibitors was uncovered so as to achieve the desired regeneration outcomes. Specifically, we explored the role of Wnt signaling inhibition on PNS regeneration by delivering Wnt inhibitors, sFRP2 and WIF1, after sciatic nerve transection and sciatic nerve crush injuries. Our results demonstrate that WIF1 promoted nerve regeneration (p < 0.05) after sciatic nerve crush injury. More importantly, we revealed the therapeutic window for the treatment of Wnt inhibitors, which is one week post sciatic nerve crush when the non-canonical receptor tyrosine kinase (Ryk) is significantly upregulated.
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spelling ntu-10356/1563512023-03-05T16:29:05Z Delivery of Wnt inhibitor WIF1 via engineered polymeric microspheres promotes nerve regeneration after sciatic nerve crush Zheng, Na Lin, Junquan Chin, Jiah Shin Wiraja, Christian Xu, Chenjie McGrouther, Duncan Angus Chew, Sing Yian School of Chemical and Biomedical Engineering Interdisciplinary Graduate School (IGS) Lee Kong Chian School of Medicine (LKCMedicine) School of Materials Science and Engineering NTU Institute for Health Technologies Engineering::Bioengineering Peripheral Nerve Injury Nerve Guidance Conduits Injuries within the peripheral nervous system (PNS) lead to sensory and motor deficits, as well as neuropathic pain, which strongly impair the life quality of patients. Although most current PNS injury treatment approaches focus on using growth factors/small molecules to stimulate the regrowth of the injured nerves, these methods neglect another important factor that strongly hinders axon regeneration - the presence of axonal inhibitory molecules. Therefore, this work sought to explore the potential of pathway inhibition in promoting sciatic nerve regeneration. Additionally, the therapeutic window for using pathway inhibitors was uncovered so as to achieve the desired regeneration outcomes. Specifically, we explored the role of Wnt signaling inhibition on PNS regeneration by delivering Wnt inhibitors, sFRP2 and WIF1, after sciatic nerve transection and sciatic nerve crush injuries. Our results demonstrate that WIF1 promoted nerve regeneration (p < 0.05) after sciatic nerve crush injury. More importantly, we revealed the therapeutic window for the treatment of Wnt inhibitors, which is one week post sciatic nerve crush when the non-canonical receptor tyrosine kinase (Ryk) is significantly upregulated. Ministry of Education (MOE) Nanyang Technological University Published version Financial support was received from SingHealth-NTU research collaborative grant (SHS-NTU/038/2016) and MOE AcRF Tier 1 grant (RG37/20). 2022-04-17T12:25:25Z 2022-04-17T12:25:25Z 2022 Journal Article Zheng, N., Lin, J., Chin, J. S., Wiraja, C., Xu, C., McGrouther, D. A. & Chew, S. Y. (2022). Delivery of Wnt inhibitor WIF1 via engineered polymeric microspheres promotes nerve regeneration after sciatic nerve crush. Journal of Tissue Engineering, 13, 1-14. https://dx.doi.org/10.1177/20417314221087417 2041-7314 https://hdl.handle.net/10356/156351 10.1177/20417314221087417 13 1 14 en SHS-NTU/038/2016 RG37/20 Journal of Tissue Engineering © 2022 The Author(s). This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). application/pdf application/pdf
spellingShingle Engineering::Bioengineering
Peripheral Nerve Injury
Nerve Guidance Conduits
Zheng, Na
Lin, Junquan
Chin, Jiah Shin
Wiraja, Christian
Xu, Chenjie
McGrouther, Duncan Angus
Chew, Sing Yian
Delivery of Wnt inhibitor WIF1 via engineered polymeric microspheres promotes nerve regeneration after sciatic nerve crush
title Delivery of Wnt inhibitor WIF1 via engineered polymeric microspheres promotes nerve regeneration after sciatic nerve crush
title_full Delivery of Wnt inhibitor WIF1 via engineered polymeric microspheres promotes nerve regeneration after sciatic nerve crush
title_fullStr Delivery of Wnt inhibitor WIF1 via engineered polymeric microspheres promotes nerve regeneration after sciatic nerve crush
title_full_unstemmed Delivery of Wnt inhibitor WIF1 via engineered polymeric microspheres promotes nerve regeneration after sciatic nerve crush
title_short Delivery of Wnt inhibitor WIF1 via engineered polymeric microspheres promotes nerve regeneration after sciatic nerve crush
title_sort delivery of wnt inhibitor wif1 via engineered polymeric microspheres promotes nerve regeneration after sciatic nerve crush
topic Engineering::Bioengineering
Peripheral Nerve Injury
Nerve Guidance Conduits
url https://hdl.handle.net/10356/156351
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