Heparin-based coacervate of bFGF facilitates peripheral nerve regeneration by inhibiting endoplasmic reticulum stress following sciatic nerve injury.

Heparin-based coacervate of bFGF facilitates peripheral nerve regeneration by inhibiting endoplasmic reticulum stress following sciatic nerve injury.
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基于肝素的 bFGF 凝聚层通过抑制坐骨神经损伤后的内质网应激促进周围神经再生

DOI:
10.18632/oncotarget.18256
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发表时间:
2017-07-18
期刊:
影响因子:
--
通讯作者:
Xiao J
Xiao J
中科院分区:
其他
文献类型:
--
作者:
Li R;Zou S;Wu Y;Li Y;Khor S;Mao Y;He H;Xu K;Zhang H;Li X;Wang J;Jiang H;Jin Q;Ye Q;Wang Z;Xiao J

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在损伤部位创造一个有利于轴突再生和髓鞘再生的微环境是治疗性神经再支配成功的关键。周围神经系统的成熟髓鞘依赖于雪旺细胞的积极参与,以形成新的细胞骨架成分和大量的相关神经营养因子。在这项研究中,我们利用了一种新的生物材料的生长因子输送组成的生物相容性聚阳离子,聚(乙撑双甘酯)和肝素。它能够结合多种生长因子,通过多价离子相互作用递送碱性成纤维细胞生长因子(bFGF)用于神经修复。体外实验表明,bFGF的载药效率可达10 μg,并能控制bFGF的释放。在体内,凝聚增强bFGF的生物利用度,从而改善运动和感觉功能。促进有髓纤维再生和髓鞘再生,促进雪旺细胞增殖。此外,bFGF凝聚体在坐骨神经损伤中的神经保护作用与减轻内质网应激信号有关。这种基于肝素的递送平台导致增加的bFGF负载效率并更好地控制其释放,这将为周围神经损伤再生治疗提供有效的策略。
Creating a microenvironment at the injury site that favors axonal regrowth and remyelinationis pivotal to the success of therapeutic reinnervation. The mature myelin sheath of the peripheral nervous system depends on active participation of Schwann cells to form new cytoskeletal components and tremendous amounts of relevant neurotrophic factors. In this study, we utilized a new biomaterial for growth factor delivery consisting of a biocompatible polycation, poly(ethylene argininylaspartatediglyceride) and heparin. It is capable of binding a variety of growth factors to deliver basic fibroblast growth factor (bFGF) through polyvalent ionic interactions for nerve repair. In vitro assays demonstrated that the bFGF loading efficiency reached 10 μg and this delivery vehicle could control the release of bFGF. In vivo, the coacervate enhanced bFGF bioavailability, which improved both motor and sensory function. It could also acceleratemyelinated fiber regeneration and remyelination and promote Schwann cells proliferation. Furthermore, the neuroprotective effect of bFGF-coacervate in sciatic nerve injury was associated with the alleviation of endoplasmic reticulum stress signal. This heparin-based delivery platform leads to increased bFGF loading efficiency and better controls its release, which will provide an effective strategy for peripheral nerve injury regeneration therapy.
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