Evidence map›Paper›PMID 42529940›Full record

ArticleAdvanced healthcare materials2026

A 3D Human Neuron-on-Chip Platform to Monitor Neuronal Injury Responses.

Ruiping Tang, Charles-Francois Latchoumane, Avi Chopra, Md Marzan Sarkar, Chunki Kim, Nathan Gonsalves, Hsueh-Fu Wu, John C Sentmanat, Alan Liu, Isha Mhatre-Winters and 7 more

Abstract read
In one paragraph

Article in Advanced healthcare materials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Ruiping TangRegenerative Bioscience Center, University of Georgia, Athens, Georgia, USA.
Charles-Francois LatchoumaneRegenerative Bioscience Center, University of Georgia, Athens, Georgia, USA.
Avi ChopraRegenerative Bioscience Center, University of Georgia, Athens, Georgia, USA.
Md Marzan SarkarRegenerative Bioscience Center, University of Georgia, Athens, Georgia, USA.
Chunki KimIsakson Center for Neurological Disease Research, Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Nathan GonsalvesRegenerative Bioscience Center, University of Georgia, Athens, Georgia, USA.
Hsueh-Fu WuCenter For Molecular Medicine, University of Georgia, Athens, Georgia, USA.
John C SentmanatG. W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Alan LiuOptics11 Life Inc., Boston, MA, USA.
Isha Mhatre-WintersIsakson Center for Neurological Disease Research, Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Aditya MishraDepartment of Statistics, University of Georgia, Athens, Georgia, USA.
Andrei G FedorovG. W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Jay M PatelDepartment of Orthopedics, Emory University School of Medicine, Atlanta, Georgia, USA.
Nadja ZeltnerCenter For Molecular Medicine, University of Georgia, Athens, Georgia, USA.
Steven L SticeRegenerative Bioscience Center, University of Georgia, Athens, Georgia, USA.
Jason R RichardsonIsakson Center for Neurological Disease Research, Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Lohitash KarumbaiahRegenerative Bioscience Center, University of Georgia, Athens, Georgia, USA.ORCID https://orcid.org/0000-0002-7274-811X

Funding

Technology Development P2CHD086843 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AMBROSIO, FABRISIA · 2015 to 2024
$10.5M
Microglial Hv1 Proton Channel as a Mediator of Environmentally-Induced Neuroinflammation and NeurodegenerationR01ES033892 · NIEHS · UNIVERSITY OF GEORGIA · PI Jason R Richardson, Long-Jun Wu · 2022 to 2026
$3.4M
Creating Endogenous Stem Cell Niches to Promote Functional Brain Repair Post-TBIR01NS099596 · NINDS · UNIVERSITY OF GEORGIA · PI KARUMBAIAH, LOHITASH · 2017 to 2021
$1.6M
Investigating cerebrovascular dysfunction and cerebral atrophy in severe traumatic brain injuryR21NS130468 · NINDS · UNIVERSITY OF GEORGIA · PI KARUMBAIAH, LOHITASH · 2023 to 2023
$379k
Alliance for Regenerative Rehabilitation Research and Training technology development awardDianne Isakson Distinguished Professorship awardNational Institute of Health (NIH)- National Institute of Neurological Disorders and Stroke R01ES033892National Institute of Health (NIH)- National Institute of Neurological Disorders and Stroke R01NS099596National Institute of Health (NIH)- National Institute of Neurological Disorders and Stroke R21NS130468National Science Foundation (NSF) - Engineering Research Center (ERC) for Cell Manufacturing Technologies NSF-ERC1648035NICHD NIH HHS P2C HD086843NIEHS NIH HHS R01 ES033892NINDS NIH HHS R01 NS099596NINDS NIH HHS R21 NS130468
6 · The paper itself

Abstract

Traumatic brain injury (TBI) is a major cause of neurological dysfunction and long-term neurodegeneration, yet the intrinsic neuronal contributions to TBI pathophysiology remain incompletely defined. Here, we present a novel Neuron-on-Chip microfluidic device and weight-drop impactor platform that can be used to mechanically injure mature human prefrontal cortex neurons (hPFCs) embedded in three-dimensional (3D) hydrogels, enabling the study of injury responses in pure neuronal cultures. We assessed real-time calcium dynamics across 13 metrics of single-cell and network activity, revealing a biphasic injury response: an early phase (0.5-24 h) characterized by excitotoxicity, hyper-synchronized bursting, and network collapse; and a late phase (8 d) marked by sustained depolarization and structural remodeling. Secretome profiling revealed progressive elevations in extracellular pT181 and total Tau from days 1 to 5 post-injury. Cytokine analysis identified early (24 h) elevations in IP-10, IL-10, IFNα2, and NCAM, and late increases (8 d) in CXCL9 and MPO, linking neuronal activity changes to stage-specific inflammatory signaling. Immunocytochemistry and immunoblotting confirmed temporally ordered upregulation of calpain-1 and active caspase-3 (days 1-3), phosphorylated Tau (AT8+, days 5-8), and neurofibrillary tangle-like Tau aggregates (NFT+, day 8). These findings establish our platform as a scalable microphysiological model for probing the dynamic cellular and molecular sequelae of neuronal response to injury, offering insights into neurodegeneration and opportunities for therapeutic discovery.

Indexed as

Brain Injuries, TraumaticLab-On-A-Chip DevicesNeuronsCalciumCells, CulturedCytokinesHumansMicrophysiological SystemsPrefrontal CortexCalciumCytokinescalcium imagingneurodegenerationNeuron‐on‐chipnew approach methodologies (NAMs)traumatic brain injury

Identifiers

PMID42529940
PMCPMC13507570

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.