Three-dimensional neural constructs

A novel platform for neurophysiological investigation

Hillary R. Irons, D. Kacy Cullen, Nicholas P. Shapiro, Nevin A Lambert, Robert H. Lee, Michelle C. LaPlaca

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Morphological and electrophysiological properties of neural cells are substantially influenced by their immediate extracellular surroundings, yet the features of this environment are difficult to mimic in vitro. Therefore, there is a tremendous need to develop a new generation of culture systems that more closely model the complexity of nervous tissue. To this end, we engineered novel electrophysiologically active 3D neural constructs composed of neurons and astrocytes within a bioactive extracellular matrix-based scaffold. Neurons within these constructs exhibited extensive 3D neurite outgrowth, expressed mature neuron-specific cytoskeletal proteins, and remained viable for several weeks. Moreover, neurons assumed complex 3D morphologies with rich neurite arborization and clear indications of network connectivity, including synaptic junctures. Furthermore, we modified whole-cell patch clamp techniques to permit electrophysiological probing of neurons deep within the 3D constructs, revealing that these neurons displayed both spontaneous and evoked electrophysiological action potentials and exhibited functional synapse formation and network properties. This is the first report of individual patch clamp recordings of neurons deep within 3D scaffolds. These tissue engineered cellular constructs provide an innovative platform for neurobiological and electrophysiological investigations, serving as an important step towards the development of more physiologically relevant neural tissue models.

Original languageEnglish (US)
Pages (from-to)333-341
Number of pages9
JournalJournal of Neural Engineering
Volume5
Issue number3
DOIs
StatePublished - Sep 15 2008

Fingerprint

Neurons
Clamping devices
Tissue
Scaffolds
Nerve Tissue
Cytoskeletal Proteins
Patch-Clamp Techniques
Neurites
Astrocytes
Synapses
Action Potentials
Extracellular Matrix
Proteins

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cellular and Molecular Neuroscience

Cite this

Three-dimensional neural constructs : A novel platform for neurophysiological investigation. / Irons, Hillary R.; Cullen, D. Kacy; Shapiro, Nicholas P.; Lambert, Nevin A; Lee, Robert H.; LaPlaca, Michelle C.

In: Journal of Neural Engineering, Vol. 5, No. 3, 15.09.2008, p. 333-341.

Research output: Contribution to journalArticle

Irons, Hillary R. ; Cullen, D. Kacy ; Shapiro, Nicholas P. ; Lambert, Nevin A ; Lee, Robert H. ; LaPlaca, Michelle C. / Three-dimensional neural constructs : A novel platform for neurophysiological investigation. In: Journal of Neural Engineering. 2008 ; Vol. 5, No. 3. pp. 333-341.
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