NIH VideoCast - Mimicking the Cellular Microenvironment with 3D Hydrogels Enables Target Discovery & Drug Screening

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Mimicking the Cellular Microenvironment with 3D Hydrogels Enables Target Discovery & Drug Screening

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Air date:	Tuesday, May 9, 2023, 1:00:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 137 (78 Live, 59 On-demand)
Category:	Special
Runtime:	01:00:43
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Biomedical Engineering Scientific Interest Group Drug discovery in cancer typically involves screening cells grown on 2-dimensional, hard plastic dishes; however, since human tissue is neither 2D nor plastic, this environment does not sufficiently emulate human disease. To overcome this limitation, we designed materials (i.e., hydrogels) for 3-dimensional cell culture with the goal of screening cells in an environment that mimics that of native tissue. With 3D cell culture, we gain an understanding of both cell invasion and cell viability, thereby providing insights that are inherently limited with traditional 2D cell culture. To achieve a suitable environment, we synthesized hyaluronan-based hydrogels because hyaluronan is often over-expressed in invasive tumours including those in the breast, brain and lung. To facilitate cell invasion and remodeling of the matrix, the hydrogels are crosslinked with peptides that can be degraded by matrix metalloproteinases (MMPs) secreted by the cells. We use either Diels-Alder or oxime click chemistry to crosslink our hydrogels while also including polymers that provide viscoelasticity, thereby enabling cells to remodel the 3D hydrogel environment. Thus, cells can invade into the hydrogel by either actively degrading it enzymatically or through ameboid movement. To enhance cell adhesion, the hydrogels are modified with proteins and/or peptides; to facilitate cell invasion, the hydrogels are modified with growth factor concentration gradients. Importantly, only diseased, and not healthy, cells migrate into the hydrogels. Using well-defined hyaluronan-based hydrogels, we investigate invasion in the context of breast cancer, brain cancer, lung cancer cell and their response to different therapeutic treatments. In the context of Hodgkin’s lymphoma, we investigate macrophage invasion and whether drug treatments can change polarization and invasion. For more information go to https://oir.nih.gov/sigs/biomedical-engineering-scientific-interest-group

NLM Title:	Mimicking the cellular microenvironment with 3D hydrogels enables target discovery & drug screening / Molly Shoichet.
Author:	Shoichet, M S. National Institutes of Health (U.S.). Biomedical Engineering Scientific Interest Group,
Publisher:
Abstract:	(CIT): Biomedical Engineering Scientific Interest Group Drug discovery in cancer typically involves screening cells grown on 2-dimensional, hard plastic dishes; however, since human tissue is neither 2D nor plastic, this environment does not sufficiently emulate human disease. To overcome this limitation, we designed materials (i.e., hydrogels) for 3-dimensional cell culture with the goal of screening cells in an environment that mimics that of native tissue. With 3D cell culture, we gain an understanding of both cell invasion and cell viability, thereby providing insights that are inherently limited with traditional 2D cell culture. To achieve a suitable environment, we synthesized hyaluronan-based hydrogels because hyaluronan is often over-expressed in invasive tumours including those in the breast, brain and lung. To facilitate cell invasion and remodeling of the matrix, the hydrogels are crosslinked with peptides that can be degraded by matrix metalloproteinases (MMPs) secreted by the cells. We use either Diels-Alder or oxime click chemistry to crosslink our hydrogels while also including polymers that provide viscoelasticity, thereby enabling cells to remodel the 3D hydrogel environment. Thus, cells can invade into the hydrogel by either actively degrading it enzymatically or through ameboid movement. To enhance cell adhesion, the hydrogels are modified with proteins and/or peptides; to facilitate cell invasion, the hydrogels are modified with growth factor concentration gradients. Importantly, only diseased, and not healthy, cells migrate into the hydrogels. Using well-defined hyaluronan-based hydrogels, we investigate invasion in the context of breast cancer, brain cancer, lung cancer cell and their response to different therapeutic treatments. In the context of Hodgkin"s lymphoma, we investigate macrophage invasion and whether drug treatments can change polarization and invasion.For more information go to https://oir.nih.gov/sigs/biomedical-engineering-scientific-interest-group.
Subjects:	Cellular Microenvironment Drug Delivery Systems Drug Evaluation, Preclinical Hydrogels--therapeutic use
Publication Types:	Lecture Webcast

NLM Classification:	QV 785
NLM ID:	9918625744906676
CIT Live ID:	49617
Permanent link:	https://videocast.nih.gov/watch=49617

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