Meet SynVivo at SHOCK 2025 in Boston, MA

May 31 – June 3, 2025

Poster Presentation

Monday, June 2, 2025 | 7:30 AM – 9:00 AM

Poster Session: 2

Session Room: Avenue 34 (Lobby Level)

“QUANTITATIVE ASSESSMENT OF LEUKOCYTE-ENDOTHELIAL INTERACTIONS IN WHOLE BLOOD CIRCULATED THROUGH A VASCULARIZED BRAIN-LUNG ORGAN-ON-CHIP MODEL“

Introduction: Microphysiological systems (MPS) that model the structural and functional aspects of the blood-brain barrier (BBB) are crucial for evaluating drug safety and efficacy in neuroinflammation. The peripheral immune system and bloodstream play a critical role in pathogen-induced inflammation, but many commercially available MPS do not integrate key blood components (e.g., red blood cells, platelets, and plasma proteins) that are essential for accurately modeling peripheral immune dynamics. To address these gaps, the SynVivo multiorgan platform combines vascularized organ-on-chip (OOC) models of the brain, lung, and peripheral immune cells in blood, enabling the evaluation of peripheral immune function in response to inflammation. The platform consists of two independently accessible OOCs, which can be treated separately with proinflammatory cytokines or pathogens. The OOCs are then fluidically connected through systemic circulation driven by an on-platform peristaltic pump. This study aims to assess the potential of this interconnected, vascularized human brain and small airway lung-on-a-chip model for evaluating barrier function and leukocyte adhesion/migration following exposure to inflammatory cytokines and circulating whole blood.

Methods: The human BBB-on-chip tri-culture model was developed using the SynBBB OOC and primary brain endothelial cells, astrocytes, and pericytes.  The human lung-on-chip model was developed using the SynRAM OOC with lung epithelial and endothelial cells seeded in microvasculature patterns obtained from in vivo capillary beds. The lung tissue was exposed via the vasculature to a cytokine cocktail for 4 hours, followed by circulation of the inflammatory responses through interconnection of the brain and lung tissues.  Following fluorescent labeling of PBMCs, whole blood was introduced into the vasculature and circulated through both tissues. The integrated tissues were assessed for leukocyte adhesion/migration after inflammatory insult and cytokine levels in lung and brain tissues.

Results: Prior to cytokine treatment, microvascular lumens were established under physiological shear stress conditions to induce tight barrier formation, resulting in a measurable decrease in paracellular permeability to tracers under flow conditions.  Inflammatory cytokines increased leukocyte adhesion to inflamed endothelium in both lung and brain vasculature as compared to untreated controls. Inflammatory cytokines and chemokine levels increased in both lung and brain tissues thus establishing an inflammatory cascade in the lung-brain axis.

Conclusions: These findings suggest that the SynVivo multiorgan platform can recapitulate the physiological characteristics of the BBB and lung tissue in vivo and offer a more predictive platform for assessing therapeutics that resolve leukocyte-mediated microvascular endothelial dysfunction.