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

Authors Song J, Li X, Li Y, Che J, Li X, Zhao X, Chen Y, Zheng X, Yuan W

Received 11 January 2017

Accepted for publication 3 April 2017

Published 2 June 2017 Volume 2017:12 Pages 4195—4208

DOI https://doi.org/10.2147/IJN.S132190

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lakshmi Kiran Chelluri

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang

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

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