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Microfluidic generation of biomaterial gradients for control of neurite outgrowth
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Text
TitleInfo
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Title
Microfluidic generation of biomaterial gradients for control of neurite outgrowth
Identifier
(type = local)
ETD_1209
Identifier
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000050466a
Language
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eng
Genre
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theses
Subject
(ID = SBJ-1);
(authority = ETD-LCSH)
Topic
Microfluidics
Subject
(ID = SBJ-1);
(authority = ETD-LCSH)
Topic
Neurons--Growth
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Biomedical Engineering
Abstract
Enhancing and directing axon regeneration through an injury site represents a prime goal for therapies following nerve or spinal cord injury. The objective of this thesis is to develop a system to create durotactic and haptotactic gradients with a biomaterial scaffold for control of neural cell behavior. Gradients of mechanical properties and adhesion are generated in a 3D collagen gel using microfluidics. To spatially control the mechanical properties, gradients of genipin - a naturally occurring, cell-tolerated crosslinking agent - are created in 3D through a fibrillar collagen gel using a simple source-sink network. Durotactic gradients of mechanical properties are evaluated by measuring genipin-induced fluorescence, which we demonstrated can be correlated to the rheological properties of the collagen gel. Neurite growth from chick dorsal root ganglia was assayed in gradients and appropriate controls. Neurite growth was biased down a gradient of stiffness of ~60Pa/mm towards a more compliant region, and neurites were significantly longer in this direction than up the gradient and than in uniform conditions without crosslinking. Haptotactic gradients are generated by first grafting laminin derived peptides, IKVAV and YIGSR, onto the collagen backbone using 1-ethyl-3-(3-Dimethylaminopropyl) carbodiimide (EDC). Peptide-grafted collagen solutions are mixed with untreated collagen in the network Neurite outgrowth was enhanced in all laminin peptide-grafted collagen gradient conditions compared to the untreated collagen controls. Neurite growth was more responsive to gradients of YIGSR than IKVAV. Enhanced growth was observed in all YIGSR-grafted conditions with the greatest bias in the steepest gradient of (24.7 ??g/ml/mm). Enhanced growth was also observed in IKVAV-grafted collagen conditions, but stunted growth occurred in collagen with uniform IKVAV presentation, implying IKVAV may be too 'sticky' for neurite outgrowth at the highest concentration studied. Since both peptides are present on the whole-length laminin molecule, the results suggest that gradients of laminin would be sub-optimal because of the contradiction in the response to the two peptides. These results demonstrate that neurite growth can be enhanced and directed by durotactic and haptotactic gradients, and suggest that including a combination of these gradients in regenerative therapies may accelerate nerve and spinal cord regeneration.
PhysicalDescription
Extent
ix, 124 p. : ill.
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Note
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Ph.D.
Note
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Includes bibliographical references (p. 115-122).
Note
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by Harini Sundararaghavan
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Sundararaghavan
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Harini
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author
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Harini Sundararaghavan
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Shreiber
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David
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chair
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Advisory Committee
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David I Shreiber
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Shinbrot
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Troy
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internal member
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Advisory Committee
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Troy Shinbrot
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(type = family)
Langrana
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Noshir
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internal member
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Advisory Committee
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Noshir Langrana
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Firestein
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Bonnie
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outside member
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Advisory Committee
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Bonnie Firestein
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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school
OriginInfo
DateCreated
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2008
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2008-10
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xx
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NjNbRU
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Rutgers University Electronic Theses and Dissertations
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ETD
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
(type = local)
rucore19991600001
Identifier
(type = doi)
doi:10.7282/T3RX9CC4
Genre
(authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
Copyright
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Copyright protected
Availability
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Open
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Non-exclusive ETD license
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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ETD
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3338240
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