Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush

Jialin Song,1,2 Xueyang Li,3 Yingli Li,4,5 Junyi Che,6 Xiaoming Li,6 Xiaotian Zhao,6 Yinghui Chen,7,* Xianyou Zheng,1,* Weien Yuan6,* 1Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 2Department of Orthopedics, Shanghai University of Medicine a...

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Autores principales: Song J, Li X, Li Y, Che J, Zhao X, Chen Y, Zheng X, Yuan W
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:c66c902e460c4360975bcc9964fe78302021-12-02T07:28:29ZBiodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush1178-2013https://doaj.org/article/c66c902e460c4360975bcc9964fe78302017-06-01T00:00:00Zhttps://www.dovepress.com/biodegradable-and-biocompatible-cationic-polymer-delivering-microrna-2-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jialin Song,1,2 Xueyang Li,3 Yingli Li,4,5 Junyi Che,6 Xiaoming Li,6 Xiaotian Zhao,6 Yinghui Chen,7,* Xianyou Zheng,1,* Weien Yuan6,* 1Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 2Department of Orthopedics, Shanghai University of Medicine and Health, Shanghai, Sixth People’s Hospital East Campus, Shanghai, 3Department of Plastic and Reconstructive Surgery, Xuzhou Medical College Affiliated Hospital, Xuzhou, Jiangsu, 4Department of Plastic Surgery, The General Hospital of Jinan Military Command, Jinan, Shandong, 5Department of Plastic Surgery, Chang Hai Hospital, Second Military Medical University, 6School of Pharmacy, Shanghai Jiao Tong University, 7Department of Neurology, Jinshan Hospital, Fudan University, JinShan District, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: MicroRNA (miRNA) has great potential to treat a wide range of illnesses by regulating the expression of eukaryotic genes. Biomaterials with high transfection efficiency and low toxicity are needed to deliver miRNA to target cells. In this study, a biodegradable and biocompatible cationic polymer (PDAPEI) was synthetized from low molecular weight polyethyleneimine (PEI1.8kDa) cross-linked with 2,6-pyridinedicarboxaldehyde. PDAPEI showed a lower cytotoxicity and higher transfection efficiency than PEI25kDa in transfecting miR-221/222 into rat Schwann cells (SCs). The upregulation of miR-221/222 in SCs promoted the expression of nerve growth factor and myelin basic protein in vitro. The mouse sciatic nerve crush injury model was used to evaluate the effectiveness of PDAPEI/miR-221/222 complexes for nerve regeneration in vivo. The results of electrophysiological tests, functional assessments, and histological and immunohistochemistry analyses demonstrated that PDAPEI/miR-221/222 complexes significantly promoted nerve regeneration after sciatic nerve crush, specifically enhancing remyelination. All these results show that the use of PDAPEI to deliver miR-221/222 may provide a safe therapeutic means of treating nerve crush injury and may help to overcome the barrier of biomaterial toxicity and low efficiency often encountered during medical intervention. Keywords: miR-221/222, PDAPEI, nerve regeneration, remyelinationSong JLi XLi YChe JLi XZhao XChen YZheng XYuan WDove Medical PressarticlemiR-221/222PDAPEInerve regenerationremyelinationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4195-4208 (2017)
institution DOAJ
collection DOAJ
language EN
topic miR-221/222
PDAPEI
nerve regeneration
remyelination
Medicine (General)
R5-920
spellingShingle miR-221/222
PDAPEI
nerve regeneration
remyelination
Medicine (General)
R5-920
Song J
Li X
Li Y
Che J
Li X
Zhao X
Chen Y
Zheng X
Yuan W
Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush
description Jialin Song,1,2 Xueyang Li,3 Yingli Li,4,5 Junyi Che,6 Xiaoming Li,6 Xiaotian Zhao,6 Yinghui Chen,7,* Xianyou Zheng,1,* Weien Yuan6,* 1Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 2Department of Orthopedics, Shanghai University of Medicine and Health, Shanghai, Sixth People’s Hospital East Campus, Shanghai, 3Department of Plastic and Reconstructive Surgery, Xuzhou Medical College Affiliated Hospital, Xuzhou, Jiangsu, 4Department of Plastic Surgery, The General Hospital of Jinan Military Command, Jinan, Shandong, 5Department of Plastic Surgery, Chang Hai Hospital, Second Military Medical University, 6School of Pharmacy, Shanghai Jiao Tong University, 7Department of Neurology, Jinshan Hospital, Fudan University, JinShan District, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: MicroRNA (miRNA) has great potential to treat a wide range of illnesses by regulating the expression of eukaryotic genes. Biomaterials with high transfection efficiency and low toxicity are needed to deliver miRNA to target cells. In this study, a biodegradable and biocompatible cationic polymer (PDAPEI) was synthetized from low molecular weight polyethyleneimine (PEI1.8kDa) cross-linked with 2,6-pyridinedicarboxaldehyde. PDAPEI showed a lower cytotoxicity and higher transfection efficiency than PEI25kDa in transfecting miR-221/222 into rat Schwann cells (SCs). The upregulation of miR-221/222 in SCs promoted the expression of nerve growth factor and myelin basic protein in vitro. The mouse sciatic nerve crush injury model was used to evaluate the effectiveness of PDAPEI/miR-221/222 complexes for nerve regeneration in vivo. The results of electrophysiological tests, functional assessments, and histological and immunohistochemistry analyses demonstrated that PDAPEI/miR-221/222 complexes significantly promoted nerve regeneration after sciatic nerve crush, specifically enhancing remyelination. All these results show that the use of PDAPEI to deliver miR-221/222 may provide a safe therapeutic means of treating nerve crush injury and may help to overcome the barrier of biomaterial toxicity and low efficiency often encountered during medical intervention. Keywords: miR-221/222, PDAPEI, nerve regeneration, remyelination
format article
author Song J
Li X
Li Y
Che J
Li X
Zhao X
Chen Y
Zheng X
Yuan W
author_facet Song J
Li X
Li Y
Che J
Li X
Zhao X
Chen Y
Zheng X
Yuan W
author_sort Song J
title Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush
title_short Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush
title_full Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush
title_fullStr Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush
title_full_unstemmed Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush
title_sort biodegradable and biocompatible cationic polymer delivering microrna-221/222 promotes nerve regeneration after sciatic nerve crush
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/c66c902e460c4360975bcc9964fe7830
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AT liy biodegradableandbiocompatiblecationicpolymerdeliveringmicrorna221222promotesnerveregenerationaftersciaticnervecrush
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AT lix biodegradableandbiocompatiblecationicpolymerdeliveringmicrorna221222promotesnerveregenerationaftersciaticnervecrush
AT zhaox biodegradableandbiocompatiblecationicpolymerdeliveringmicrorna221222promotesnerveregenerationaftersciaticnervecrush
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AT zhengx biodegradableandbiocompatiblecationicpolymerdeliveringmicrorna221222promotesnerveregenerationaftersciaticnervecrush
AT yuanw biodegradableandbiocompatiblecationicpolymerdeliveringmicrorna221222promotesnerveregenerationaftersciaticnervecrush
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