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The impact of the physical microenvironment on trophoblast function

Award Number: F31HD105398
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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The impact of the physical microenvironment on trophoblast function - The placenta is a critical organ that develops during pregnancy to allow the fetus to obtain nutrients and remove waste. The placenta acts as both a gatekeeper and an endocrine organ; two functions which are vital for a healthy pregnancy. However, how the placenta acts after perturbations of the system is not well known due to ethical concerns regarding obtaining tissue throughout all stages of pregnancy and poor in vitro or ex vivo systems that lack the level of control and physiological relevance needed. In preliminary studies, we have successfully made an in vitro microfluidic placenta model that allows for culture of three different cell types (trophoblast, fibroblasts, and endothelial cells) within natural protein gels. Microfluidic channels incorporate shear stress into the model and the tri-cell culture allows for cell-cell communication which have both been shown to be vital for physiologically relevant trophoblast phenotype. Cells can be cultured on natural substrates derived from human placenta with (1) ease, (2) in parallel, (3) with tight control, and (4) without the need for technical expertise in microfluidics. The model can easily be updated to study many mechanistic and fundamental properties of the healthy or dysregulated placenta. One disease that can cause complications during pregnancy, preeclampsia (PE), is associated with disrupted placentation from limited remodeling of the uterine wall; a process vital to ensure healthy placental tissue, proper oxygen concentration, and appropriate amount of shear stress within the placenta. Due to the lack of uterine remodeling, placental extracellular matrix (ECM) is stiffened via fibrosis, oxygen tension is lowered, and shear stress is increased. We hypothesize that these physical microenvironmental cues within the placenta cause disrupted trophoblast function that can be mechanistically examined in our novel microfluidic placenta model. In Aim 1 we will alter our microfluidic device in order to test how ECM dysregulation alters trophoblast function. We will make stromal layers of healthy or pathogenic stiffnesses from both collagen-I and human placenta derived ECM. Placental derived ECM will enable us to test how the full milieu of the placenta ECM impacts trophoblast function, while the collagen-I ECM will allow for tighter control of the environment. In Aim 2 we will test the closely tied relationship between oxygen tension and shear stress on trophoblast function. Devices will be cultured at healthy or pathogenic oxygen tension and shear stress to elucidate if their stimuli are synergistic. These studies will demonstrate the ease of our system in being able to control the microphysical properties of the system for elucidation of mechanistic properties of multi-cell models of the placenta.


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: 2024 ( Subtotal = -$43,682 )
2024	2023	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Child Health and Human Development Extramural Research	001	3	6/24/2024	NON-COMPETING CONTINUATION	-$29,585
2024	2022	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Child Health and Human Development Extramural Research	000	2	6/24/2024	NON-COMPETING CONTINUATION	-$14,097
														Subtotal = -$43,682

Issue Date FY: 2023 ( Subtotal = $29,585 )
2023	2023	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Child Health and Human Development Extramural Research	000	3	3/7/2023	NON-COMPETING CONTINUATION	$47,694
2023	2023	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Child Health and Human Development Extramural Research	001	3	8/29/2023	NON-COMPETING CONTINUATION	-$18,109
														Subtotal = $29,585

Issue Date FY: 2022 ( Subtotal = $46,752 )
2022	2022	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Child Health and Human Development Extramural Research	000	2	4/18/2022	NON-COMPETING CONTINUATION	$46,753
2022	2022	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Child Health and Human Development Extramural Research	001	2	5/25/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = $46,752

Issue Date FY: 2021 ( Subtotal = $46,036 )
2021	2021	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Child Health and Human Development Extramural Research	001	1	3/31/2021	NEW	$0
2021	2021	UNIVERSITY OF DELAWARE	220 HULLIHEN HALL	NEWARK	DE	19716	NEW CASTLE	USA	Child Health and Human Development Extramural Research	000	1	3/31/2021	NEW	$46,036
														Subtotal = $46,036

Grand Total All Awards = $78,691

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The impact of the physical microenvironment on trophoblast function

Award Number: F31HD105398

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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