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Characterizing the feedback loop between cells and the pericellular region during cell-material interactions

Award Number: R35GM147043
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Characterizing the feedback loop between cells and the pericellular region during cell-material interactions - Project summary Interactions between human mesenchymal stem cells (hMSCs) and their environment are a main factor in the function of these cells. Although the importance of cell-material interactions is well established, it has been difﬁ- cult to characterize this complex interplay, especially in vivo. During in vivo experiments, a stem cell treatment's efﬁcacy can be assessed, but the underlying cellular processes and change in the surrounding microenvironment that leads to these outcomes remain a black box. Positive outcomes may result from these experiments even if there is loss of function or integrity in the tissue due to failed cell-material interactions, making aspects of the stem cell treatment ineffective and potentially unnecessary. Since real-time measurement of these interactions has not been realized in vivo, in vitro models provide an alternative approach to measuring cell-material inter- actions in both 2D and 3D culture. The use of scaffolds to mimic aspects of native tissue provide controlled environments where cell-material interactions can be quantitatively characterized. These scaffolds are used for 3D cell encapsulation and are designed to be remodeled by cells. This creates a feedback loop where the cell remodels the pericellular region and responds to the dynamically changing cues in the environment. Real-time characterization of these dynamic cell-material interactions continues to be a challenge. We propose to char- acterize dynamic cell-material interactions by measuring real-time hMSC-mediated scaffold remodeling using microrheological characterization and the resulting cellular processes using cell staining and inhibition. We will use an hMSC-laden synthetic hydrogel scaffold that mimics aspects of native microenvironments to present cues to cells. To characterize hMSC function, we will use techniques including cell staining and pharmacological inhibi- tion of molecules for cellular contractility and matrix adhesion. Our unique approach will characterize the scaffold microenvironment in real-time during cell-material interactions. We will use multiple particle tracking microrhe- ology (MPT) to measure hMSC-mediated scaffold remodeling and degradation. This technique quantiﬁes the spatio-temporal evolution of the rheology in the pericellular region, which is part of the feedback loop that deﬁnes cell-material interactions. Together, these measurements will provide a relationship between cellular function and cell-engineered pericellular rheology as the complexity of the scaffold microenvironment is increased. The pro- posed research program will focus on characterizing cell-material interactions during speciﬁc critical processes that are not fully understood. The processes we will study are (1) cellular adhesion, (2) hMSC motility in re- sponse to scaffold viscoelasticity and (3) hMSC-material interactions when signaling molecules are presented in the environment. The proposed work will support the overarching goal of understanding the fundamentals of cell-material interactions and the inﬂuence on basic cellular processes.


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 = $373,000 )
2026	2026	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	6	6/25/2026	NON-COMPETING CONTINUATION	$373,000
														Subtotal = $373,000

Issue Date FY: 2025 ( Subtotal = $373,382 )
2025	2025	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	000	5	7/25/2025	NON-COMPETING CONTINUATION	$373,382
														Subtotal = $373,382

Issue Date FY: 2024 ( Subtotal = $376,733 )
2024	2024	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	005	4	6/27/2024	NON-COMPETING CONTINUATION	$373,382
2024	2023	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Biomedical Research and Research Training	001	2	4/26/2024	SUPPLEMENT FOR EXPANSION	-$163,666
2024	2023	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	002	3	4/26/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$543,494
2024	2023	PURDUE UNIVERSITY	2550 NORTHWESTERN AVE # 1100	WEST LAFAYETTE	IN	47906	TIPPECANOE	USA	Biomedical Research and Research Training	004	3	6/11/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$35,730
2024	2023	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Biomedical Research and Research Training	000	2	4/26/2024	NON-COMPETING CONTINUATION	-$376,477
2024	2022	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Biomedical Research and Research Training	003	1	6/11/2024	NEW	-$35,730
														Subtotal = $376,733

Issue Date FY: 2023 ( Subtotal = $540,143 )
2023	2023	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Biomedical Research and Research Training	001	2	7/25/2023	SUPPLEMENT FOR EXPANSION	$163,666
2023	2023	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Biomedical Research and Research Training	000	2	6/30/2023	NON-COMPETING CONTINUATION	$376,477
														Subtotal = $540,143

Issue Date FY: 2022 ( Subtotal = $377,136 )
2022	2022	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Biomedical Research and Research Training	000	1	7/25/2022	NEW	$377,136
														Subtotal = $377,136

Grand Total All Awards = $2,040,394

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Characterizing the feedback loop between cells and the pericellular region during cell-material interactions

Award Number: R35GM147043

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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