Using NGF heparin-poloxamer thermosensitive hydrogels to enhance the nerve regeneration for spinal cord injury.
Using NGF heparin-poloxamer thermosensitive hydrogels to enhance the nerve regeneration for spinal cord injury.
复制标题
使用NGF肝素-泊洛沙姆温敏水凝胶增强脊髓损伤的神经再生
DOI：
10.1016/j.actbio.2015.10.014
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发表时间：
2016-01
影响因子：
9.7
通讯作者：
Lu CT
中科院分区：
文献类型：
--
作者：
Zhao YZ;Jiang X;Xiao J;Lin Q;Yu WZ;Tian FR;Mao KL;Yang W;Wong HL;Lu CT
神经生长因子（NGF）在脊髓损伤（SCI）的治疗中具有广阔的应用前景，但由于其理化稳定性差、穿透血脊髓屏障的能力低而受到限制。构建了一种新型的肝素-泊洛沙姆（HP）温敏水凝胶，用于促进脊髓损伤后神经生长因子（NGF）的再生。制备了NGF-HP温敏性水凝胶，并对其凝胶化温度、流变行为和微观形态进行了研究。通过在损伤空间中原位注射来实现局部NGF递送至损伤脊髓。用PC 12细胞体外摄取NGF-HP水凝胶。观察神经生长因子-羟脯氨酸水凝胶对大鼠脊髓损伤的病理学特征和神经元再生的影响。分析内质网应激诱导的细胞凋亡，探讨其在脊髓损伤再生中的相关机制。NGF-HP水凝胶在体外显示了良好的形态和稳定的NGF生物活性。NGF-HP水凝胶联合应用可显著提高细胞对NGF的摄取率（P<0.05），且无明显细胞毒性。NGF-HP水凝胶组神经元功能和组织形态学均有明显改善。与游离HP水凝胶组和NGF治疗组相比，NGF-HP水凝胶组对大鼠脊髓损伤模型中胶质瘢痕的形成有明显的抑制作用。NGF-HP的神经保护作用与抑制慢性内质网应激诱导的细胞凋亡有关。HP水凝胶结合原位注射技术可能是一种有效的将NGF输送到损伤部位的方法，这将为SCI的再生提供一种有效的策略。
Nerve growth factor (NGF) has potential in spinal cord injury (SCI) therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Novel heparin-poloxamer (HP) thermo-sensitive hydrogel was constructed to enhance the NGF regeneration on SCI. NGF-HP thermo-sensitive hydrogel was prepared and related characteristics including gelation temperature, rheological behavior and micromorphology were measured. Local NGF delivery to the injured spinal cord was achieved by in situ injection in the injured space. The cellular uptake of NGF-HP hydrogel was evaluated with PC12 cells in vitro. Pathologic characteristics and neuron regeneration effects on the SCI rats were studied to evaluate the enhanced therapy of NGF-HP hydrogel. Endoplasmic reticulum (ER) stress-induced apoptosis was analyzed to explore the related mechanism in SCI regeneration. NGF-HP hydrogel showed good morphology and stable bioactivity of NGF in vitro. NGF-HP hydrogel combined treatment significantly enhanced the efficiency of NGF cellular uptake (P<0.05) without obvious cytotoxicity. Significant improvements in both neuron functions and tissue morphology on the SCI rats were observed in NGF-HP hydrogel group. Compared with free HP hydrogel and NGF treatment groups, NGF-HP hydrogel group showed significant inhibition on the formation of glial scars in the extreme crushed rat SCI model. The neuroprotective effects of NGF-HP were related to the inhibition of chronic ER stress-induced apoptosis. HP hydrogel combined with orthotopic injection technique might be an effective method to deliver NGF into the injured site, which will provide an effective strategy for SCI regeneration.
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影响因子：
6.2
作者：
Niu, Guoguang;Zhang, Hongbin;Yang, Huai
通讯作者：
Yang, Huai
影响因子：
9.7
作者：
Park, Kyung Min;Lee, Sang Young;Park, Ki Dong
通讯作者：
Park, Ki Dong
影响因子：
6.2
作者：
Brandl, Ferdinand;Hammer, Nadine;Goepferich, Achim
通讯作者：
Goepferich, Achim
影响因子：
5.3
作者：
Girard, C;Bemelmans, AP;Lachapelle, F
通讯作者：
Lachapelle, F
影响因子：
3.4
作者：
Menei, P;Montero-Menei, C;Bunge, MB
通讯作者：
Bunge, MB