ISurTec is seeking SBIR funding to continue the development of a versatile bioartificial brain slice scaffold, designed for use in electrophysiological drug-screening assays. Acute brain slices, prepared from rats or mice, are currently the `gold standard' preparation for characterizing neural tissue responses to drugs, toxins, or other agents. However, the limited number of brain slices produced per animal, coupled with the high costs of animal care and use, remains a major limitation of this approach. Furthermore, due to interspecies genetic variation, preclinical data acquired through the use of acute brain slices will usually be of limited predictive power for human clinical trials and postmarket surveillance. The Phase I project demonstrated that 3D scaffolds containing an open-field architecture ?blueprint? can spontaneously induce hippocampal CA3-CA1-like neural circuits from dissociated hippocampal cells. These bioartificial brain slices reliably generate field excitatory postsynaptic potentials (fEPSPs) that are sensitive to glutamate receptor antagonists. Phase I was accomplished through simultaneous control over the nanotopography and surface chemistry using ISurTec's photoreactive nanofibers. In Phase II, we will modify the scaffold design to improve both its performance and its manufacturability as well as develop and optimize protocols for culturing Glutamatergic, GABAergic, and Dopaminergic hNPCs on the scaffolds in conjunction with hGPCs. The optimized protocols will be used for assay validation, and the bioartificial human brain slices will be field tested for both drug development and toxicology. The human bioartificial brain slice is expected to be a valuable tool for drug development concerning a wide variety of human neurological diseases and disorders, including addiction, ADD/ADHD, depression, Parkinson's disease, pain processing, and schizophrenia. Our technology will advance the field of Central Nervous System (CNS) Drug Development by overcoming the following two limitations of acute slices derived from rodents: (1) its limited human relevance and (2) its high burden and cost of animal care compliance and oversight. Relevant to the current brain slice technique, our technique is low-cost and decreases animal sacrifice while increasing the predictive power of human neural progenitor cell assays. This SBIR project will create a bioartificial brain slice scaffold for patterning 3-dimensional, highly laminar open field arrays of human neuronal co-cultures for electrophysiology.
The use of acute brain slices ? thin sections of living brain tissue harvested from rats or mice ? is the most accessible and physiologically relevant drug-screening assay available to approximate systems-level effects on the central nervous system (CNS) and spinal cord. However, this approach suffers from high costs due to animal care, use, and oversight as well as limited clinical relevance (non- human tissue). This SBIR project will create a bioartificial brain slice scaffold for patterning 3-dimensional, highly laminar open field arrays of human neuronal co- cultures for electrophysiology.
