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A bioengineered blood-brain barrier-on-a-chip microphysiological system for improved drug screening in primary brain tumors

Award Number: R21NS146966
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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A bioengineered blood-brain barrier-on-a-chip microphysiological system for improved drug screening in primary brain tumors - PROJECT SUMMARY Glioblastoma (GB) is the most common brain cancer that originates within the brain. It is difficult to treat, and unfortunately recurs in all patients, even after remission. When it recurs, it is even more difficult to treat. Therefore, it is essentially lethal in almost every patient. Even with aggressive surgery and chemoradiotherapy, median survival for GB patients is only 14.5 months. Despite advances in managing cancers, only 4 new treatments have been FDA-approved for GB in the last 3 decades. A major challenge in translating therapies into the clinic is modeling the cellular variability of GBs, as well as accounting for the blood brain barrier (BBB). GBs evolve both over time and in response to treatment, making selection of treatments a challenge. In addition, the different subpopulations of tumor cells have different impacts on BBB biology and functionality, which impacts the ability of treatments to reach the tumor cells inside of the brain behind the BBB. Another reason why new therapeutics have failed in clinical trials is that the models that were used for preclinical studies were not representative of GB and the brain. While both animal models and traditional cell cultures have yielded important medical advances, they don’t accurately recapitulate human physiology in many cases. More recent 3D human cell-based models of GB, such as organoids, are improvements over 2D cell cultures, but have generally failed to consider the many additional components of the GB/brain environment (cells and physical scaffolding in which the cells reside) surrounding tumors as well as the presence of the BBB. Integration of these key components in a GB model has the potential to provide an in vitro platform technology that better represents GB tumors as they occur in human patients, thus serving as an improved GB model for applications such as drug development, disease modeling, and personalized medicine. We will use our expertise in organ-on-a-chip bioengineering and GB biology to generate a BBB and GB-on-a-chip (BBB-GOC) system that includes not just GB cells, but heterogeneous GB populations, additional brain cells such as astrocytes and pericytes, and the BBB itself. Our team recently developed a BBB-on-a-chip (BBB-OC). In the proposed studies we will integrate 3D human GB cells structures. Aim 1 will assess how the integration of a GB cells impacts baseline BBB function. Aim 2 will validate the BBB-GOC platform by assessing efficacy of the currently used chemotherapy (temozolomide) versus a promising therapy not currently used since it can’t cross the BBB (paclitaxel) for GB cell killing. Aim 3 will expand the impact of our project to evaluation our platform in the context of cellular immunotherapy, which is the cutting edge therapeutic in many cancer types but has yet to be deployed effectively in GB. If successful, our ultimate goal is to utilize the BBB-GOC with cells derived from patient debulking surgeries to screen treatments to determine the best treatment for each individual patient in a personalized manner in a system that takes into consideration drug mass transport properties in the context of the BBB.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $424,333 )
2026	2026	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/27/2026	NEW	$424,333
														Subtotal = $424,333

Grand Total All Awards = $424,333

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A bioengineered blood-brain barrier-on-a-chip microphysiological system for improved drug screening in primary brain tumors

Award Number: R21NS146966

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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