Formation of tissue models in 3 dimensions is more effective in recapitulating structure and function compared to their 2-dimensional (2D) counterparts. Formation of 3D engineered tissue to control shape and size can have important implications in biomedical research and in engineering applications such as biological soft robotics. While neural spheroids routinely are created during differentiation processes, further geometric control of in vitro neural models has not been demonstrated. Here, we present an approach to form functional in vitro neural tissue mimic (NTM) of different shapes using stem cells, a fibrin matrix, and 3D printed molds. We used murine-derived embryonic stem cells for optimizing cell-seeding protocols, characterization of the resulting internal structure of the construct, and remodeling of the extracellular matrix, as well as validation of electrophysiological activity. Then, we used these findings to bio-fabricate these constructs using neurons derived from human embryonic stem cells. This method can provide a large degree of design flexibility for development of in vitro functional neural tissue models of varying forms for therapeutic biomedical research, drug discovery, and disease modeling, and engineering applications.

Original languageEnglish (US)
Pages (from-to)25932-25940
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number51
StatePublished - Dec 17 2019


  • Biofabrication
  • HESC
  • MESC
  • Neural construct
  • Tissue mimic

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Engineering geometrical 3-dimensional untethered in vitro neural tissue mimic'. Together they form a unique fingerprint.

Cite this