Mechanically Induced Neurological Trauma Chip
Overview
The Blood-Brain Barrier Model MINT Chip is a microphysiological organ-on-chip platform designed to replicate the structure and function of the human blood-brain barrier (BBB). The BBB is a highly selective interface that regulates the transport of molecules between the bloodstream and the brain, and its dysfunction is associated with numerous neurological conditions. Traditional models often fail to capture the complexity of the BBB, particularly the interactions between multiple cell types and the effects of mechanical forces. The MINT Chip addresses these limitations by incorporating multicellular co-culture systems, physiological flow conditions, and mechanical injury simulation, enabling a more accurate representation of the in vivo environment. This platform is particularly suited for studying traumatic brain injury (TBI), where mechanical forces disrupt BBB integrity and lead to downstream neurological effects. By enabling controlled simulation of injury and real-time measurement of barrier function, the MINT Chip allows researchers to investigate both primary and secondary injury mechanisms, as well as evaluate drug permeability and therapeutic interventions.
Key Benefits
Traumatic Brain Injury Modeling
Simulates mild to severe TBI and its impact on BBB integrity.
Drug Permeability Testing
Evaluates transport of therapeutics across the BBB.
Co-Culture Physiological Accuracy
Mimics interactions between brain and vascular cells.
Dynamic Flow Conditions
Recreates realistic vascular environments.
Model Overview
The platform features a multicellular co-culture system consisting of brain microvascular endothelial cells and supporting vascular cells, separated by a permeable membrane.Fluid flow mimics blood circulation, while mechanical systems allow simulation of traumatic injury conditions. The model incorporates human iPSC-derived cell types to better replicate human physiology.Barrier integrity is quantitatively assessed using TEER measurements and permeability assays, enabling real-time evaluation of BBB function.
Validation
human brain (green) and blood vessel (red) cells grown in compartments with a permeable membrane
DAPI (nucleus) + ZO-1 (brain cell tight junctions)+ NG-2 (blood vessel cells)
The MINT Chip has been validated using human cell-based co-culture systems, demonstrating the formation of a functional and physiologically relevant blood-brain barrier.Fluorescent staining confirms the presence of key cellular markers, including tight junction proteins (ZO-1) and supporting vascular cell markers (NG-2), indicating proper structural organization of the barrier.Functional validation shows that the model exhibits selective permeability and measurable barrier integrity, consistent with in vivo BBB behavior. Following mechanically induced injury, the system demonstrates clear disruption of barrier function, including decreases in TEER (transendothelial electrical resistance) and increased permeability.Importantly, the platform has been tested across varying levels of injury severity, with results showing graded physiological responses. This confirms its ability to model not only healthy BBB function but also the progressive breakdown associated with traumatic brain injury.
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