Development of an implant-linked alginate matrix for cell-mediated neuronal protection

本项目的目的是开发基于藻酸盐基质的细胞介导的神经保护。采用细胞藻酸盐涂层功能化的人工耳蜗电极作为模型系统。人工耳蜗是感觉性听力损失的标准治疗方法。它刺激初级听觉通路的神经元，即螺旋神经节细胞，从而在患者中引起声音感觉。其中，人工耳蜗的成功与否取决于可用螺旋神经节细胞的数量和兴奋性。生长因子脑源性神经营养因子（BDNF）对螺旋神经节细胞有保护作用，可能有助于增加人工耳蜗植入的成功率。对于临床有用的生长因子，长期应用是可取的。BDNF的长期给药可以通过细胞介导的内源性生产来实现。然而，必须保护bdnf合成细胞免受受体生物的免疫反应。必须避免细胞不受控制的增殖和迁移。藻酸盐可以作为因子生成细胞的基质，从而满足上述要求。该项目的里程碑是：1)电极载体的永久海藻酸盐涂层的开发；2)对人间充质干细胞进行修饰，使其产生BDNF并向软骨细胞分化；3)体外评价功能化电极的神经保护性能；4)确定电刺激对海藻酸盐和细胞的影响，以及涂层对电参数的影响，5)在动物模型中检测生物效应。

The aim of this project is to develop a cell-mediated neuroprotection based on an alginate matrix. The cochlear implant electrode which is functionalized with a cell-alginate coating is used as model system.The cochlear implant is the standard therapy for sensory hearing loss. It stimulates the neurons of the primary auditory pathway, the spiral ganglion cells, and thus elicits a sound sensation in the patient. Amongst others, the success of a cochlear implant depends on the number and the excitability of the available spiral ganglion cells.The growth factor brain-derived neurotrophic factor, BDNF, has a protective effect on spiral ganglion cells and could potentially help to increase the success of a cochlear implant. In the case of a growth factor useful for clinical purposes, a long-term application is desirable.Long-term administration of BDNF could be achieved by cell-mediated endogenous production. However, the BDNF-synthesizing cells must be protected from immune responses of the recipient organism. An uncontrolled proliferation and migration of the cells must be avoided. Alginate could serve as a matrix for the factor-producing cells, so that the requirements described above can be fulfilled.The milestones of this project are 1) development of a permanent alginate coating of the electrode carrier; 2) modification of human mesenchymal stem cells which might be obtained in an autologous fashion to produce BDNF and differentiate into chondrocytes; 3) evaluation of the neuroprotective properties of the functionalized electrode in vitro; 4) determination of the influence of the electrical stimulation onto the alginate and cells, and of the coating onto the electric parameters and 5) detection of the biological effect in animal models.