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Preparation of a bioactive cochlea implant electrode by electrophoretic deposition of DNA-functionalized nanoparticles

DNA功能化纳米颗粒电泳沉积制备生物活性人工耳蜗电极

基本信息

批准号：
328855289
负责人：
Professor Dr. Matthias Epple
金额：
--
依托单位：
Klinik für Hals-Nasen-Ohrenheilkunde
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/328855289?language=en
关键词：
Preparation bioactive cochlea implant electrode

项目摘要

So far, no study on the coating of a Cochlea-Implant electrode with DNA-transfecting nanoparticles has been performed. In this project, an electrode shall be coated with nanoparticles that carry DNA encoding for the proteins NT-3 and BDNF and studied in vitro. A surface-mediated transfection will lead to a release of NT-3 and BDNF into the surrounding tissue. This will enhance the growth of neurites towards the electrode and improve the hearing ability of the patient. For this, the physical, chemical and biological properties of the nanoparticles (especially transfection efficiency and cytotoxicity) shall be studied. Thereafter, the DNA-functionalized nanoparticles will be deposited by electrophoretic deposition in different layers on the substrate. The efficiency of the surface-mediated transfection from different layers (sequential release of nanoparticles) will be studied. The goal is the investigation of the deposited functionalized nanoparticles in a spiral ganglial cell culture. As spiral ganglia cells are finally differentiated cells, they will be obtained from neonatal mouse cochlea and studied in a dissociated cell culture. It will be determined whether the transfection with NT-3 and BDNF is successful. Finally, cultures of spiral ganglia explants will be prepared. They will be co-cultured on a nanoparticle-coated Cochlea-Implant electrode. It will be investigated whether the growth of neurites towards the functionalized electrode is enhanced. Especially important are the neurite growth behavior and the interaction of neurites with Schwann cells as promotors of regeneration.

到目前为止，还没有进行关于用DNA捕获纳米颗粒涂覆耳蜗植入物电极的研究。在这个项目中，电极将被涂上纳米颗粒，这些纳米颗粒携带编码蛋白质NT-3和BDNF的DNA，并在体外进行研究。表面介导的转染将导致NT-3和BDNF释放到周围组织中。这将促进神经突向电极的生长，并提高患者的听力。为此，应研究纳米颗粒的物理、化学和生物学性质（特别是转染效率和细胞毒性）。此后，DNA功能化的纳米颗粒将通过电泳沉积在基底上的不同层中。将研究来自不同层的表面介导的转染的效率（纳米颗粒的顺序释放）。我们的目标是在螺旋神经节细胞培养的沉积功能化纳米粒子的调查。由于螺旋神经节细胞是最终分化的细胞，因此将从新生小鼠耳蜗中获得并在分离的细胞培养物中进行研究。将确定用NT-3和BDNF转染是否成功。最后，准备螺旋神经节外植体的培养物。它们将在纳米颗粒涂层的耳蜗植入电极上共培养。将研究神经突朝向功能化电极的生长是否增强。尤其重要的是神经突生长行为和神经突与作为再生促进剂的雪旺细胞的相互作用。