Promotion of neurite outgrowth is an important limiting step for regeneration in nerve injury and depends strongly on the local expression of nerve growth factor (NGF). The rational design of bioactive materials is a promising approach for the development of novel therapeutic methods for nerve regeneration, and biomaterials capable of presenting NGF to nerve cells are especially suitable for this purpose. In this study, we show bioactive peptide amphiphile (PA) nanofibers capable of promoting neurite outgrowth by displaying high density binding epitopes for NGF. A high-affinity NGF-binding sequence was identified by phage display and combined with a beta-sheet forming motif to produce a self-assembling PA molecule. The bioactive nanofiber had higher affinity for NGF compared to control nanofibers and in vitro studies revealed that the NGF binding peptide amphiphile nanofibers (NGFB-PA nanofiber) significantly promote the neurite outgrowth of PC-12 cells. In addition, the nanofibers induced differentiation of PC-12 cells into neuron-like cells by enhancing NGF/high-activity NGF receptor (TrkA) interactions and activating MAPK pathway elements. The NGFB-PA nanofiber was further shown as a promising material to support axonal outgrowth from primary sensory neurons. These materials will pave the way for the development of new therapeutic agents for peripheral nervous system injuries.

中文翻译：

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通过合理设计的NGF-β结合肽纳米纤维的神经突生长的促进†

促进神经突生长是神经损伤中再生的重要限制步骤，并且强烈依赖于神经生长因子（NGF）的局部表达。合理设计生物活性材料是开发用于神经再生的新型治疗方法的有前途的方法，并且能够向神经细胞呈递NGF的生物材料特别适合于此目的。在这项研究中，我们显示了生物活性肽两亲（PA）纳米纤维能够通过展示NGF的高密度结合表位来促进神经突生长。通过噬菌体展示鉴定高亲和力的NGF结合序列，并与形成β-折叠的基序结合以产生自组装的PA分子。与对照纳米纤维和体外相比，具有生物活性的纳米纤维对NGF的亲和力更高研究表明，NGF结合肽两亲纳米纤维（NGFB-PA纳米纤维）显着促进PC-12细胞的神经突生长。此外，纳米纤维通过增强NGF /高活性NGF受体（TrkA）相互作用并激活MAPK途径元素，诱导PC-12细胞分化为神经元样细胞。NGFB-PA纳米纤维被进一步证明是一种有希望的材料，可以支持来自初级感觉神经元的轴突生长。这些材料将为开发用于周围神经系统损伤的新治疗剂铺平道路。