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Biomimetic Electrospun Fibers for Cancer Cell Migration, Chemotaxis, and Anti-Metastatic Drug Testing

Nelson, Mark Tyler
http://orcid.org/0000-0002-7255-4964
http://rave.ohiolink.edu/etdc/view?acc_num=osu1429031970

Abstract Details

2015, Doctor of Philosophy, Ohio State University, Biomedical Engineering.
Electrospun fibers are currently utilized in a wide range of biomedical and commercial applications. The unique microstructure and morphology of electrospun nanofibers produce nanoscale inter-fiber porosity and large surface areas that promote cellular attachment and growth. This is significant in applications requiring improved drug adsorption, infusion, and release for drug delivery, and as an aid in filtration processes. Numerous polymers have been electrospun allowing considerable mechanical and chemical tailoring, thus expanding the already wide-range of applications. Polycaprolactone (PCL) is commonly used due to its inherent long-term stability, mechanical strength, and cellular integration in tissue engineering, drug delivery, and other-biomedical applications. In addition, electrospun fiber microstructure and morphology closely resembles and mimics the extracellular matrix (ECM) of human tissues and tumors. In my work, supercritical carbon dioxide (SCCO2) mediated infusion of small molecules; gelatin and thermal-sintering facilitated mechanical stability; aligned electrospun PCL fiber topography stimulated tumor cell migration was studied. Supercritical fluids present an approach capable of enhancing the chemical activity of composite tissue engineering scaffolds. Previous attempts to embed test compounds into electrospun polycaprolactone (PCL) alone at pressures above 6.20 MPa and temperatures above 25°C resulted in loss of biomimicry. Gelatin shrinks and dehydrates in the presence of SCCO2 restricting PCL polymer-chain mobility preventing melting and allowing enhanced small molecule infusion and release. In addition gelatin-PCL blended nanofibers allow for increased stability of modulus through hydrolytic induced crystallinity, that drives polymer chain rearrangement and mobility. Thermally driven-sintering below the melting point of PCL increased crystallinity and enhanced nanofiber strength. High-throughput in vitro tools allowing rapid, accurate, and novel anti-metastatic drug screening are grossly overdue. Conversely, aligned nanofiber constitutes a prominent topographic component of the late-stage tumor margin extracellular matrix. This parallel suggests that the use of a synthetic ECM in the form of a nanoscale model could provide a convenient means of testing the migration potentials of cancer cells to achieve a long-term goal of providing clinicians with an in vitro platform technology testing the efficacy of novel experimental anti-metastatic compounds. Further investigation in the cellular and genetic mechanisms that enhance the ability of tumor cells to sense topographical and chemotactic cues will aid in determining novel targets for future anti-metastatic drug development. The reported work displays our progression of: (1) supercritical fluids technology for infusing small molecules into nanofiber for drug delivery purposes, (2) sintering and composite engineering mechanisms that drive crystallinity and mechanical stability, and (3) novel aligned nanofiber cell migration assay development to study tumor cell chemotaxis, genetic modulation, and anti-metastatic drug testing.
John Lannutti (Advisor)
Tim Eubank (Committee Member)
Heather Powell (Committee Member)
Samir Ghadiali (Committee Member)
343 p.
Biomedical Engineering; Biomedical Research; Cellular Biology; Materials Science
electrospinning; drug delivery; ex vivo; cell migration; tumor microenvironment; bioengineering

Recommended Citations

Citations

  • Nelson, M. T. (2015). Biomimetic Electrospun Fibers for Cancer Cell Migration, Chemotaxis, and Anti-Metastatic Drug Testing [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429031970

    APA Style (7th edition)

  • Nelson, Mark. Biomimetic Electrospun Fibers for Cancer Cell Migration, Chemotaxis, and Anti-Metastatic Drug Testing . 2015. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1429031970.

    MLA Style (8th edition)

  • Nelson, Mark. "Biomimetic Electrospun Fibers for Cancer Cell Migration, Chemotaxis, and Anti-Metastatic Drug Testing ." Doctoral dissertation, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429031970

    Chicago Manual of Style (17th edition)

osu1429031970
187
© 2015, some rights reserved.Creative Commons License Biomimetic Electrospun Fibers for Cancer Cell Migration, Chemotaxis, and Anti-Metastatic Drug Testing by Mark Tyler Nelson is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by The Ohio State University and OhioLINK.
Release 3.2.12