title: Sustained Local Release of NGF from a Chitosan-Sericin Composite Scaffold for Treating Chronic Nerve Compression.
abstract: Chronic nerve compression (CNC), a common form of peripheral nerve injury, always leads to chronic peripheral nerve pain and dysfunction. Current available treatments for CNC are ineffective as they usually aim to alleviate symptoms at the acute phase with limited capability toward restoring injured nerve function. New approaches for effective recovery of CNC injury are highly desired. Here we report for the first time a tissue-engineered approach for the repair of CNC. A genipin cross-linked chitosan-sericin 3D scaffold for delivering nerve growth factor (NGF) was designed and fabricated. This scaffold combines the advantages of both chitosan and sericin, such as high porosity, adjustable mechanical properties and swelling ratios, the ability of supporting Schwann cells growth, and improving nerve regeneration. The degradation products of the composite scaffold upregulate the mRNA levels of the genes important for facilitating nerve function recovery, including glial-derived neurotrophic factor (GDNF), early growth response 2 (EGR2), and neural cell adhesion molecule (NCAM) in Schwann cells, while down-regulating two inflammatory genes' mRNA levels in macrophages, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β). Importantly, our tissue-engineered strategy achieves significant nerve functional recovery in a preclinical CNC animal model by decreasing neuralgia, improving nerve conduction velocity (NCV), accelerating microstructure restoration, and attenuating gastrocnemius muscles dystrophy. Together, this work suggests a promising clinical alternative for treating chronic peripheral nerve compression injury.
authors.affiliation: Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Jiefang Avenue 1277, Wuhan, China 430022.|Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China 430022.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Jiefang Avenue 1277, Wuhan, China 430022.
authors.forename: Wen
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China 430022.
authors.forename: Kaixiong
authors.initials: K
authors.lastname: Tao
authors.affiliation: Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Jiefang Avenue 1277, Wuhan, China 430022.
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.affiliation: Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Jiefang Avenue 1277, Wuhan, China 430022.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Xie
authors.affiliation: Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Jiefang Avenue 1277, Wuhan, China 430022.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Jiefang Avenue 1277, Wuhan, China 430022.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China 430022.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Shuai
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China 430022.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Gao
authors.affiliation: Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Jiefang Avenue 1277, Wuhan, China 430022.
authors.forename: Panpan
authors.initials: P
authors.lastname: Chang
authors.affiliation: Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China 430022.
authors.forename: Guobin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Jiefang Avenue 1277, Wuhan, China 430022.|Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China 430022.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Jiefang Avenue 1277, Wuhan, China 430022.|Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China 430022.
authors.forename: Lin
authors.identifier: http://orcid.org/0000-0001-5716-6587
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D048271:Chitosan; D020932:Nerve Growth Factor / Q000737:chemistry*; D009416:Nerve Regeneration; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells; D047030:Sericins
chemical_list: D047030:Sericins; D048271:Chitosan; D020932:Nerve Growth Factor
keywords: NGF; chitosan-sericin scaffold; chronic nerve compression; functional restoration; tissue engineering approach