I-Corps: Neural microphysiological systems for neuropharmaceutical testing

该项目中描述的技术代表着神经“芯片上的器官”发展的重大飞跃。设计仿生3D神经模型的能力将允许快速筛选神经毒性、神经保护以及定制微环境以模拟危重疾病模型。到目前为止，只有2D体外细胞培养和动物模型可以作为临床前药物发现的工具。不幸的是，这两种选择都不能很好地转化为体内临床应用，从目前的药物失败率和飙升的研发费用来看，这一点是显而易见的。这一先进的模型将使学术界和工业界的科学家能够以独特的成本效益和及时的方式进一步研究与神经退行性病变相关的潜在机制和治疗方法。这项技术应该会增加对轴突变性、神经毒性后果和神经保护机制的分子理解。拟议技术的成功商业化将导致面向药物测试的基于服务的产品的销售。PI已经证明了微工程周围神经组织传导电诱发的复合动作电位，并申请了与细胞培养模型的制造和应用有关的临时专利。以这一发现为基础，PI建议通过在微工程大鼠组织中展示病理生理学特征来验证原型。通过联系潜在客户，PI和他的团队将评估原型的准备情况，并确定进一步的基准和设计标准。两个关键组成部分将包括提炼用于临床前筛查的最有效产出和确定最大限度地利用的实验范例。

The technology described in this project represents a significant leap forward in the development of a neural 'organ-on-a-chip'. The ability to engineer a biomimetic 3D nerve model will allow for rapid screening of neurotoxicity, neuroprotection, as well as the tailoring of the microenvironment to mimic critical disease models. To this point, only 2D in vitro cell cultures and animal models have been available as pre-clinical tools for drug discovery. Unfortunately, neither of these options translates well to in vivo clinical applications, which is apparent looking at the current failure rates of drugs as well as skyrocketing R&D expenses. This advanced model will allow both academic and industrial scientists to further study underlying mechanisms and therapies related to neurodegenerative pathologies in a uniquely cost effective and timely manner. This technology should increase the molecular understanding of axonal degeneration, neurotoxic consequences and neuroprotective mechanisms. Successful commercialization of the proposed technology will result in a service-based product marketed towards pharmaceutical testing. The PI has demonstrated that microengineered peripheral neural tissues conduct electrically-evoked compound action potentials and filed a provisional patent related to the fabrication and application of the cell culture model. With this discovery as a foundation, the PI proposes to validate a prototype by demonstrating pathophysiological signatures in microengineered rat tissues. By contacting potential customers, the PI and his team will assess the readiness of the prototype and identify further benchmarks and design criteria. Two critical components will include refining the most effective outputs utilized for preclinical screenings and identifying maximally exploitable experimental paradigms.