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Anatomically Inspired Three-dimensional Micro-tissue Engineered Neural Networks for Nervous System Reconstruction, Modulation, and Modeling
Published on: May 31, 2017
Anatomically Inspired Three-dimensional Micro-tissue Engineered Neural Networks for Nervous System Reconstruction,
Laura A Struzyna1, Dayo O Adewole1, Wisberty J Gordián-Vélez1
1Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania; Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania; Center for Neurotrauma, Neurodegeneration & Restoration, Michael J. Crescenz Veterans Affairs Medical Center.
Researchers developed micro-tissue engineered neural networks (micro-TENNs) to repair central nervous system (CNS) damage. These constructs bridge damaged areas, promoting neural network regeneration and functional recovery in the brain.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Regenerative Medicine
Background:
- Central nervous system (CNS) injuries and diseases often result in permanent functional loss due to limited neurogenesis and inhibitory environments.
- Existing strategies struggle to address both neuronal loss and axonal pathway damage simultaneously.
- Restoring complex neural circuitry requires innovative approaches that mimic natural brain architecture.
Purpose of the Study:
- To present a fabrication protocol for micro-tissue engineered neural networks (micro-TENNs).
- To demonstrate the potential of micro-TENNs for reconstructing damaged CNS pathways.
- To explore micro-TENNs as biofidelic models for in vitro neurobiological studies.
Main Methods:
- Fabrication of cylindrical hydrogel constructs with a hollow lumen using a mold and removable needle.
- Seeding dissociated neurons into the hydrogel lumen to form neuronal aggregates at the construct's ends.
- Utilizing extracellular matrix (ECM) within the lumen to support axonal outgrowth and neuronal adhesion.
Main Results:
- Successfully produced self-contained micro-TENNs with long-projecting axonal tracts mimicking brain neuroanatomy.
- Demonstrated extensive synaptic distribution and intrinsic electrical activity within the micro-TENNs via immunolabeling and calcium imaging.
- Micro-TENNs showed potential as pro-regenerative scaffolds, guiding cell migration and axonal pathfinding.
Conclusions:
- Micro-TENNs offer a promising strategy for targeted neurosurgical reconstruction of brain pathways.
- These constructs can potentially restore or modulate function in damaged neural circuitry.
- Micro-TENNs serve as valuable in vitro models for studying neurobiological phenomena and regeneration.

