Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers.

Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers.
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DOI:
10.1016/j.biomaterials.2010.10.003
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发表时间:
2011-02
期刊:
影响因子:
14
通讯作者:
Podlasek, Carol A.
Podlasek, Carol A.
中科院分区:
工程技术1区
文献类型:
--
作者:
Angeloni, Nicholas L.;Bond, Christopher W.;Tang, Yi;Harrington, Daniel A.;Zhang, Shuming;Stupp, Samuel I.;McKenna, Kevin E.;Podlasek, Carol A.

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为阴茎提供神经支配的海绵状神经(CN)的再生努力取得了最低限度的成功,几乎没有转化为改善临床结果。我们提出,Sonic hedgehog (SHH)对于维持CN完整性至关重要,并且SHH通过新型肽两亲性(PA)纳米纤维传递到CN,将促进CN再生,恢复生理功能,并防止导致勃起功能障碍(ED)的阴茎形态变化。我们进行了定位研究,在CN中抑制SHH信号,并通过线性PA凝胶(一种创新的延长释放递送方法)将SHH蛋白处理粉碎的CNs。形态学、功能和分子分析表明,SHH蛋白对维持CN结构至关重要,SHH处理促进CN再生,抑制阴茎凋亡,并在不到文献报道一半的时间内改善58%的勃起功能。这些研究表明,SHH在前列腺切除术和糖尿病患者的CN再生中具有重要的临床应用,该方法可广泛应用于再生任何周围神经,SHH是维持其结构所必需的,并且这种纳米技术蛋白质递送方法可能作为许多器官的体内递送工具广泛应用。
Efforts to regenerate the cavernous nerve (CN), which provides innervation to the penis, have been minimally successful, with little translation into improved clinical outcomes. We propose that, Sonic hedgehog (SHH), is critical to maintain CN integrity, and that SHH delivered to the CN by novel peptide amphiphile (PA) nanofibers, will promote CN regeneration, restore physiological function, and prevent penile morphology changes that result in erectile dysfunction (ED). We performed localization studies, inhibition of SHH signaling in the CN, and treatment of crushed CNs with SHH protein via linear PA gels, which are an innovative extended release method of delivery. Morphological, functional and molecular analysis revealed that SHH protein is essential to maintain CN architecture, and that SHH treatment promoted CN regeneration, suppressed penile apoptosis and caused a 58% improvement in erectile function in less than half the time reported in the literature. These studies show that SHH has substantial clinical application to regenerate the CN in prostatectomy and diabetic patients, that this methodology has broad application to regenerate any peripheral nerve that SHH is necessary for maintenance of its structure, and that this nanotechnology method of protein delivery may have wide spread application as an in vivo delivery tool in many organs.
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