In the United States, about one in five Americans above the age of 18 suffer from diagnosable neurological disorders with no cure insight. As such, new, safe, non-invasive methods for the treatment of brain disorders are critically needed. Non-invasive techniques including repetitive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation have had some success. However, progress has been limited due to poor understanding of the interactions of magnetic fields with nervous tissue. The molecular/cellular mechanisms of nervous tissue under TMS are still lacking. Hence, investigation of effects of transient magnetic fields on adult neurogenesis, cell differentiation and plasticity of nervous tissue (neurospheres) is essential in developing new treatment procedures and achieving the use of TMS as a neuromodulation tool for treating neurological disorders. The educational goal of this project is to effectively integrate research with educational activities and to train both undergraduate and graduate students in interdisciplinary studies to produce next-generation bioengineers. The PIs will develop a new Vertically Integrated Program (VIP) based on this research proposal entitled: Targeting Neurodegenerative Diseases Using Bioengineering Approaches. The VIP will unite undergraduate education and faculty research in a team-based context. The overall educational goal is to help next-generation workforce development by training students to carry out research with sound technical background and allowing them to gain hands-on laboratory skills for their advanced careers. The long-term goal is to design an automatic technical platform to synthesize a variety of in vitro central nervous system disease models to mimic in vivo conditions as closely as possible. This will facilitate the studies of TMS effects and drug screening assays for neurodegenerative disorders.
The goal of this proposal is to develop a chip-based microfluidics platform that facilitates the rapid formation of three-dimensional in vitro cell culture models of the central nervous system, which will permit the investigation of mechanisms of organ development, cellular interactions, disease model progression under magnetic field stimulation and drug treatments within de?ned microenvironments. Specifically, the proposed efforts include (1) the development of a chip consisting of microchamber arrays so that neurospheres including diseased neurospheres such as Alzheimer?s disease (AD) neurospheres can be fabricated in an efficient manner; and (2) the studies of the behavior of healthy neurospheres and AD neurospheres under transient magnetic stimulation (MS) and drug treatment using this chip. Major innovations of this proposed project can be summarized as the following: (1) Using this type of microfluidic chip, large-scale neurospheres with tunable and quantitative compositions can be synthesized rapidly and inexpensively, facilitating studies of different types of neurospheres; (2) Using a concentration gradient generator at the upper stream of this chip, a series of AD models (AD neurospheres) with known concentrations of amyloid-? and/or phosphorylated-tau can be readily fabricated; and (3) developing this chip will thus facilitate studies of the effects of both MS and drug treatment on AD models.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.