Neural Tissue Engineering Scaffolds

Neural Tissue Engineering Scaffolds

Living brain slices, typically harvested from rats or mice, are currently the ‘gold standard’ preparation for characterizing central nervous system tissue responses to drugs, toxins, or other agents. Recent advances in stem and neural progenitor cell biology enable human neurons to be produced in vitro, but these cultures have limited utility because they lack the cellular organization and physiology found in CNS brain tissue. Our research is developing 3-dimensional microarchitectural tissue scaffolds that can take dissociated human neural and glial progenitor cell populations and direct their growth and differentiation into engineered human brain tissues. These tissues, which resemble “brain slices” in that they contain naturalistic cellular organization and systems-level circuitry, are intended for use in pharmaceutical research and studies of activity-dependent synaptic plasticity. We aim to replace the use of rodent brain slices in drug discovery, reducing the need for animals in research, while also improving outcomes when developing drugs intended for human use.

Our scaffolds will be produced in a standardized format compatible with common electrophysiology equipment such as multielectrode arrays. We believe this tissue engineering scaffold for human neural circuits will be a valuable tool for drug development concerning a wide variety of human neurological diseases and disorders, including addiction, Alzheimer’s disease, depression, epilepsy, pain processing, and schizophrenia.

3D Neural Circuit-on-a-Chip for Drug Screening

The neural tissue engineering scaffolds are designed to promote 3D neural tissue formation from suspension cells. The mature neural tissue resembles the form and function of acute, ex-vivo brain slices, thus enabling the use of hiPSC-derived neural tissues for systems-level extracellular electrophysiology (i.e. evoked field excitatory post-synaptic potential assay, or “brain slice fEPSP” assay).

Pharmacological Sensitivity of Long-term Potentiation

This technology is designed to enable molecular studies of synaptic plasticity ​using tissue-engineered human neural circuits, rather than ex-vivo rodent (shown above) brain slices.

This project is supported by the National Institute of Mental Health of the National Institutes of Health under Award Number R44MH101958. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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