Sustained Local Release of NGF from a Chitosan-Sericin Composite Scaffold for Treating Chronic Nerve Compression
Sustained Local Release of NGF from a Chitosan-Sericin Composite Scaffold for Treating Chronic Nerve Compression
复制标题
壳聚糖-丝胶复合支架局部持续释放 NGF 用于治疗慢性神经压迫
DOI：
10.1021/acsami.6b14691
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发表时间：
2017
影响因子：
9.5
通讯作者：
Wang Lin
中科院分区：
文献类型：
--
作者：
Zhang Lei;Yang Wen;Tao Kaixiong;Song Yu;Xie Hongjian;Wang Jian;Li Xiaolin;Shuai Xiaoming;Gao Jinbo;Chang Panpan;Wang Guobin;Wang Zheng;Wang Lin
慢性神经卡压（CNC）是一种常见的周围神经损伤形式，常导致慢性周围神经疼痛和功能障碍。目前可用的CNC治疗方法是无效的，因为它们通常旨在缓解急性期的症状，而恢复受损神经功能的能力有限。高度期望用于CNC损伤的有效恢复的新方法。在这里，我们报告的第一次组织工程的方法修复数控。设计并制备了京尼平交联壳聚糖-丝胶蛋白三维神经生长因子（NGF）缓释支架。这种支架结合了壳聚糖和丝胶的优点，如高孔隙率，可调节的机械性能和溶胀比，支持雪旺细胞生长的能力，并促进神经再生。复合支架的降解产物上调对促进神经功能恢复重要的基因的mRNA水平，包括施万细胞中的胶质源性神经营养因子（GDNF）、早期生长反应2（EGR 2）和神经细胞粘附分子（NCAM），同时下调巨噬细胞中的两种炎性基因的mRNA水平，肿瘤坏死因子α（TNF-α），和白细胞介素-1 β（IL-1β）。重要的是，我们的组织工程策略通过减少神经痛、提高神经传导速度（NCV）、加速微结构恢复和减轻腓肠肌营养不良，在临床前CNC动物模型中实现了显著的神经功能恢复。总之，这项工作提出了一个有前途的临床替代治疗慢性周围神经压迫损伤。
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.