| NSF Org: |
DMR Division Of Materials Research |
| Recipient: |
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| Initial Amendment Date: | June 27, 2014 |
| Latest Amendment Date: | June 15, 2016 |
| Award Number: | 1410341 |
| Award Instrument: | Continuing Grant |
| Program Manager: |
Randy Duran
rduran@nsf.gov (703)292-5326 DMR Division Of Materials Research MPS Directorate for Mathematical and Physical Sciences |
| Start Date: | July 15, 2014 |
| End Date: | June 30, 2019 (Estimated) |
| Total Intended Award Amount: | $390,000.00 |
| Total Awarded Amount to Date: | $390,000.00 |
| Funds Obligated to Date: |
FY 2015 = $130,000.00 FY 2016 = $130,000.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
300 TURNER ST NW BLACKSBURG VA US 24060-3359 (540)231-5281 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
333 Kelly Hall Blacksburg VA US 24061-0001 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): |
Engineering of Biomed Systems, BIOMATERIALS PROGRAM |
| Primary Program Source: |
01001516DB NSF RESEARCH & RELATED ACTIVIT 01001617DB NSF RESEARCH & RELATED ACTIVIT |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.049 |
ABSTRACT
Non-Technical:
This award supported by the Biomaterials program in the Division of Materials Research to Virginia Polytechnic Institute and State University, is co-funded by the BME program in the Division of Chemical, Bioengineering, Environmental and Transport Systems (CBET). Liver fibrosis is a leading cause of death in the USA. Alcohol abuse, obesity, diabetes or viral infections are some initiating events that induce fibrosis. Each of these events causes severe liver inflammation, thereby altering signaling pathways leading to the initiation and progression of fibrosis. This project will use a fundamental science focused biomaterials approach to generate novel insights into the cellular and signaling mechanisms that underlie the progression of fibrosis. This project includes a K-12 outreach program. Through a one-week summer camp, the project will provide opportunities to high-school students to understand how biological membranes affect the properties of liver cells. The one-week camp will include experimental and analytical activities. The overall goal is to encourage high-school students to consider future education and careers in STEM fields
Technical:
Liver fibrosis is a leading cause of death worldwide. Some other extremely harmful conditions that result due to liver fibrosis are hepatic carcinomas, renal failure, toxin-induced comas, bleeding, and a host of metabolic disorders. This project will study the initiation and progression of liver fibrosis from a fundamental science focused biomaterials perspective. This project seeks to design engineered transitional tissues. The investigators will develop a transitional liver tissue containing a polymeric membrane that exhibits a gradient in both mechanical and chemical properties. They will seek to determine to what extent must chemical and mechanical profiles vary in the liver in order to sustain hepatic fibrosis and to understand how the major hepatic cells respond to stiffer matrices and varying chemical concentrations.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
The liver can undergo fibrosis due to a range of reasons. When the liver undergoes fibrosis it experiences changes at the chemical, physical and cellular levels. Fibrosis is a consequence of injuries sustained by the liver. Most models that probe this condition are performed in vivo. Therefore this is a critical need to design and develop in vitro models of liver fibrosis that mimic the process of a fibrosis. In this project we assembled a “transitional” tissue, which had cells exposed to different mechanical properties. We designed a 3D liver-mimetic tissue, which served as an engineered model to probe how changes in the mechanical environment affected the performance of liver cells.
We designed a polyelectrolyte multilayer membrane that exhibited a gradient in mechanical properties. This membrane upon hydration served as a protein interface found in the liver. The polyelectrolyte multilayers exhibited elastic moduli within the range of fibrotic tissues. We cultured hepatocytes, liver sinusoidal endothelial cells, liver macrophages and hepatic cells and monitored changes in their function. We observed changes in cell viability, the increase in the concentrations of inflammatory molecules, as well as changes in the mechanical properties of the polyelectrolyte membrane. The 3D cultures we designed have applications in other fields of biomedical engineering and tissue engineering as platforms to understand how mechanical changes in the microenvironment can affect cellular functions. Fibrosis occurs in a range of tissues and organs. While the changes in each tissue may differ based on the types of cells involved, the big changes in the physical environment are similar. For example, all fibrotic tissues exhibit much higher elastic moduli and changes in the protein composition of the cellular microenvironment. For these reasons we believe that our findings specifically, the changes on a temporal scale will be very useful to researchers who study fibrosis of different biological systems.
We disseminated our results to the scientific community via peer-reviewed journal publications, presentations at national conferences, seminars at universities and in publicly available graduate theses.
Last Modified: 10/27/2019
Modified by: Padmavathy Rajagopalan
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