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用于神经生长因子(NGF)控释的丝素蛋白基质

Silk fibroin matrices for the controlled release of nerve growth factor (NGF).

作者信息

Uebersax Lorenz, Mattotti Marta, Papaloïzos Michaël, Merkle Hans P, Gander Bruno, Meinel Lorenz

机构信息

Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.

出版信息

Biomaterials. 2007 Oct;28(30):4449-60. doi: 10.1016/j.biomaterials.2007.06.034. Epub 2007 Jul 23.

Abstract

Nerve conduits (NC) for peripheral nerve repair should guide the sprouting axons and physically protect the axonal cone from any damage. The NC should also degrade after completion of its function to obviate the need of subsequent explanation and should optionally be suitable for controlled drug release of embedded growth factors to enhance nerve regeneration. Silk fibroin (SF) is a biocompatible and slowly biodegradable biomaterial with excellent mechanical properties that could meet the above stated requirements. SF material (films) supported the adherence and metabolic activity of PC12 cells, and, in combination with nerve growth factor (NGF), supported neurite outgrowth during PC12 cell differentiation. NGF-loaded SF-NC were prepared from aqueous solutions of NGF and SF (20%, w/w), which were air-dried or freeze-dried (freezing at -20 or -196 degrees C) in suitable molds. NGF release from the three differently prepared SF-NC was prolonged over at least 3 weeks, but the total amount released depended on the drying procedure of the NC. The potency of released NGF was retained within all formulations. Control experiments with differently dried NGF-lactose solutions did not evidence marked protein aggregation (SEC, HPLC), loss of ELISA-reactivity or PC12 cell bioactivity. This study encourages the further exploitation of SF-NC for growth factor delivery and evaluation in peripheral nerve repair.

摘要

用于周围神经修复的神经导管(NC)应引导轴突芽生,并切实保护轴突锥体免受任何损伤。神经导管在完成其功能后还应降解,以免除后续取出的需要,并且应视情况适合于对包埋的生长因子进行可控药物释放,以促进神经再生。丝素蛋白(SF)是一种具有优异机械性能的生物相容性且可缓慢生物降解的生物材料,能够满足上述要求。SF材料(薄膜)支持PC12细胞的黏附及代谢活性,并且在与神经生长因子(NGF)联合使用时,支持PC12细胞分化过程中的神经突生长。载有NGF的SF-NC由NGF和SF(20%,w/w)的水溶液制备而成,这些溶液在合适的模具中进行风干或冷冻干燥(在-20或-196℃冷冻)。从三种不同制备的SF-NC中释放的NGF至少延长了3周,但释放的总量取决于神经导管的干燥程序。所有制剂中释放的NGF效力均得以保留。对不同干燥的NGF-乳糖溶液进行的对照实验未显示出明显的蛋白质聚集(尺寸排阻色谱法、高效液相色谱法)、酶联免疫吸附测定反应性丧失或PC12细胞生物活性丧失。本研究鼓励进一步开发用于周围神经修复中生长因子递送和评估的SF-NC。

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