Research Mentor Name

Marly Coe

Research Mentor Email Address

marly.coe@tufts.edu

Institution / Department

Tufts University Department of Biomedical Engineering

Document Type

Research Abstract

Research Type

basicbio

Level of Research

no

Abstract

Traumatic brain injury (TBI) causes permanent cell death and can lead to long-term cognitive dysfunction, with no available treatments to repair the damaged brain tissue. Methods to track and understand TBI in humans are severely limited by the inaccessibility of living brain tissue, creating a need for in vitro model systems to study cellular mechanisms of degeneration and regeneration following injury. Here we describe methods to establish a 3D human brain tissue model, consisting of a silk-collagen composite scaffold seeded with human neurons, astrocytes, and microglia, to study neuro-regeneration after TBI. Step-by-step fabrication, injury, and analytical assessments of the 3D “triculture” system are described. Using this tissue model system, we demonstrate that glial cells promote regeneration of neuronal networks within the injury site over several weeks post-injury. Further, we found that regenerating networks in the 3D triculture tissues did not secrete early markers of neurodegenerative disease, but displayed signs of excitatory/inhibitory imbalance. The model system includes mechanical stability that enables physiologically relevant impact injury and long-term culture capability, as well as a modular design that allows tunability of cell contents, extracellular matrix composition, and scaffold properties. Further studies using this regenerative human in vitro platform could inform future reparative treatments to improve long-term TBI patient outcomes.

Disciplines

Medicine and Health Sciences

Comments

The authors thank Dr. Dana Cairns for providing the hiNSCs used throughout this study, as well as the Tufts Advanced Microscopic Imaging Core staff for training and assistance with the confocal microscope. Figure 1b,c were made using BioRender.com.

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