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Therapeutic nanoscale matrimeres

Award Number: R01EB034507
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Therapeutic nanoscale matrimeres - PROJECT SUMMARY The extracellular matrix in tissue is significantly disrupted in many disease conditions, but it is essential for cells to function. Endothelial cells become leaky when they no longer receive functional matrix signals upon tissue injury. Failure to restore endothelial barrier function can result in persistent edema, long-term tissue damage, and irreversible tissue fibrosis. Since many organs are highly vascularized, there is a need to find a general solution to treat tissue injury by restoring matrix-mediated signaling. There is currently no effective strategy to achieve this goal, since the activation of matrix signaling pathways requires the delivery of matrix molecules with proper molecular conformation and physiochemical properties. Here, we define a novel class of cell-secreted, non-vesicular nanoparticles that bear matrix molecules, which we call matrimeres. Our preliminary data show that mesenchymal stromal cells naturally secrete matrimeres consisting of fibronectin and DNA, which can directly activate endothelial cells to restore junctions disrupted by endotoxemia-induced injury. Importantly, we show that functional matrimeres can be reconstituted from purified fibronectin protein and genomic DNA fragments in a chemical environment similar to secretory compartments in cells. We will build on these results to test the hypothesis that fibronectin matrimeres treat tissue injury by restoring endothelial barrier function. In Aim 1, we will determine how fibronectin matrimeres restore endothelial barrier function after inflammatory injury in the lungs. In Aim 2, we will investigate biogenesis mechanisms of fibronectin matrimeres in mesenchymal stromal cells. In Aim 3, we will engineer synthetic matrimeres that restore endothelial barrier function. We predict that highly functional nanomedicine can be developed based on the fundamental insight that cells are able to recycle and repackage matrix molecules into nanoparticles by complexing with DNA fragments, which circulate in the body and play a homeostatic role in limiting vascular permeability. The project is highly multidisciplinary in that it will employ a combination of expertise in nanoscale biology, nanotechnology, chemical, biomaterials, computational, advanced imaging, cellular and molecular biology, and in vivo approaches to address the specific aims. The results will help develop a number of fundamental concepts of matrimeres in terms of their mechanisms of action, biogenesis, and reverse engineering. Success of the project will also enable the generalization of matrimeres as natural nanomedicine to deliver macromolecules for improved regenerative outcomes.


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 = -$8,845 )
2026	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	2/2/2026	NON-COMPETING CONTINUATION	-$362,651
2026	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	2/3/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$353,806
														Subtotal = -$8,845

Issue Date FY: 2025 ( Subtotal = $447,718 )
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	3/20/2025	NON-COMPETING CONTINUATION	$402,946
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	8/13/2025	NON-COMPETING CONTINUATION	$44,772
														Subtotal = $447,718

Issue Date FY: 2024 ( Subtotal = $438,765 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	4/23/2024	NON-COMPETING CONTINUATION	$438,765
														Subtotal = $438,765

Issue Date FY: 2023 ( Subtotal = $447,718 )
2023	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	3/9/2023	NEW	$447,718
														Subtotal = $447,718

Grand Total All Awards = $1,325,356

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Therapeutic nanoscale matrimeres

Award Number: R01EB034507

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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