Sustained Local Release of NGF from a Chitosan–Sericin Composite Scaffold for Treating Chronic Nerve Compression

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• 作者：Lei Zhang ; Wen Yang ; Kaixiong Tao ; Yu Song ; Hongjian Xie ; Jian Wang ; Xiaolin Li ; Xiaoming Shuai ; Jinbo Gao ; Panpan Chang ; Guobin Wang ; Zheng Wang ; Lin Wang
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2017
• 出版时间：February 1, 2017
• 年：2017
• 卷：9
• 期：4
• 页码：3432-3444
• 全文大小：950K
• ISSN：1944-8252

文摘

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.