
NSF Org: |
DMR Division Of Materials Research |
Recipient: |
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Initial Amendment Date: | February 11, 2008 |
Latest Amendment Date: | January 17, 2012 |
Award Number: | 0748340 |
Award Instrument: | Continuing Grant |
Program Manager: |
Joseph A. Akkara
DMR Division Of Materials Research MPS Directorate for Mathematical and Physical Sciences |
Start Date: | February 1, 2008 |
End Date: | January 31, 2013 (Estimated) |
Total Intended Award Amount: | $500,000.00 |
Total Awarded Amount to Date: | $500,000.00 |
Funds Obligated to Date: |
FY 2009 = $100,000.00 FY 2010 = $100,000.00 FY 2011 = $100,000.00 FY 2012 = $100,000.00 |
History of Investigator: |
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Recipient Sponsored Research Office: |
3400 N CHARLES ST BALTIMORE MD US 21218-2608 (443)997-1898 |
Sponsor Congressional District: |
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Primary Place of Performance: |
3400 N CHARLES ST BALTIMORE MD US 21218-2608 |
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): | BIOMATERIALS PROGRAM |
Primary Program Source: |
01000910DB NSF RESEARCH & RELATED ACTIVIT 01001011DB NSF RESEARCH & RELATED ACTIVIT 01001112DB NSF RESEARCH & RELATED ACTIVIT 01001213DB 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
This Career award by the Biomaterials program in the Division of Materials Research to Johns Hopkins University aims to test the hypothesis that the presentation of topographical and surface tethered biochemical cues by nanofibers can potentiate neural stem cell (NSC) adhesion, contact guidance, and growth factor signaling, and thereby regulate NSC adhesion, proliferation, differentiation, and migration. To achieve this goal, polycaprolactone nanofibers are prepared by electrospinning and they are surface-conjugated with adhesion molecules (laminin and fibronectin) and fibroblast growth factor-2 with controlled concentration gradients and distributions. This platform will be used to systematically analyze the effect of nanofiber-presented topographical and biochemical cues, either independently or in combination, on NSC adhesion, proliferation, differentiation and migration. These studies are expected to demonstrate the ability to manipulate NSC behavior through the synergistic integration of the various cues. Neural stem cells offer tremendous potential for treating degenerative diseases and traumatic injuries of the central nervous system. Their clinical application, however, faces the challenges of insufficient cell number and poor control over NSC state and fate, problems due partly to our limited understanding of signaling regulation of NSCs by the extra cellular matrix microenvironment cues.
Scientific impact of the proposal is in the field of regenerative medicine by providing improvement in health care and quality of life. The education and outreach components of the proposal include a number of novel ideas and applications, and are well integrated with the projects research plans. Active participation with Women in Science and Engineering program to attract high-school female students to science and bio/engineering interface, association with clinical partners, and introduction of undergraduates to patenting and intellectual property development are other parts of this project. In addition, a new bioengineering course will be developed at the University.
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 goal of the research project is to understand the local regulation of the proliferation and differentiation of neural stem cells by nanofiber-presented topographical and biochemical cues. Major research outcomes include (1) development of a functional electrospun fiber matrix platform with precise control over their diameters, alignment, and surface functionalities tailored for adult neural stem cells (NSCs) and ESC-derived NSCs and neural crest stem cells (NCSCs), (2) demonstration of nanofiber diameter and alignment as important parameters influencing NSC-differentiation, and neural crest stem cell differentiation, (3) understanding the role of nanofiber cue in regulating beta-catenin level and influencing the fate specification and differentiation, (4) the synergistic effect between the topographical cue (nanofiber matrix) and the biochemical cue (insulin like growth factor 1, IGF-1, and noggin) in promoting Schwann cell differentiation, (5) identification of optimal nanofiber-culture protocols for oligodendrocyte and Schwann cell differentiation, (6) development of degradable nanofiber matrix for ex vivo neural stem cell differentiation culture, and (7) demonstration of the aligned nanofiber matrix as a guidance cue for peripheral nerve regeneration. Major education and outreach achievements include (1) development of the “Biomaterials Lab” curriculum and a teaching lab for the course, which has enrolled more than 56 students over the past five years; (2) promotion of diversity and participation of undergraduate students (total of 22) and high school students (total of 9) from underrepresented minority groups (total of 14 female, Hispanic, and African American), (3) enhancing undergraduate student research opportunities by serving as the co-PI of NSF Johns Hopkins University REU-Site Program in Nanotechnology for Biology and Medicine, (4) mentoring several student design teams for bioengineering innovation—two of the teams won national awards and one team won the Coulter Development Award, and (5) creating opportunities for students and postdoctoral fellows to work with biotech corporate partners—this experience provided a valuable and unique training to students on engineering at work in biotech industry. Four primary papers (leading role), six secondary papers (minor role) and three review papers have been published and three more in preparation. Four graduate students and two postdoctoral fellows have been partially supported by this grant.
Last Modified: 05/02/2013
Modified by: Hai-Quan Mao
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