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Fabrication of Injectable Cell Carriers Based on Polymer Thin Film Dewetting

Song, Hokyung

Abstract Details

2014, Doctor of Philosophy, University of Akron, Chemical Engineering.
This dissertation describes the development of high aspect ratios of injectable cell carriers fabricated based on simple and cost-effective techniques utilizing dewetting of polymer thin films. The high aspect ratios of injectable cell carriers would be vital for tissue regeneration such as muscles, neurons, and blood vessels. Current injection based approaches have not truly mimicked the anisotropic structures. As results, in this study, two different injectable cell carriers have been developed to achieve these important structures. Prior to generating the structures, the stability of poly(lactic-co-glycoic acid) (PLGA) films in common aqueous solutions to further utilize it for fabricating scaffolds. The results showed that, for relatively thinner films (< 30 nm), dewetting of PLGA films on Silicon-wafer under both DI-water and phosphate buffered saline (PBS) was mainly controlled by electrostatic interactions; for thicker films (> 30 nm), van der Waals interactions governed the instability. Under both BSA solution and culture medium, dewetting of PLGA films was suppressed and occurred only for a relative short period (= 24 h), and was found to be mainly controlled by electrostatic interactions. The suppression was caused by the changed surface properties (e.g., surface energy and zeta potential) of the polymer films due to protein adsorption. The first construct was fibrous injectable cell/polymer micro-constructs. Patterned PLGA films were fabricated via featured polydimethylsiloxane (PDMS) stamps. The work focused on fibrous film generation by rupturing thin layers between thick patterns via dewetting. To maintain control over the continuous fibrous film generation, the imprinted films were first dewetted, and then placed on agarose-coated surfaces. As a result, cells seeded on the samples migrated to the PLGA surfaces during incubation time. A three days of incubation of cells on the bundle was found to be optimal, and using a tapered syringe barrel increased the injectability almost by two fold. More importantly, in vitro study using an alginate gel micro-environment showed a relatively high viability, ~78%, resulted for cells on the bundle after 7 days of incubation post injection, while the viability of free cells decreased to ~51% 7 days post injection (vs. 93% immediately after injection). Furthermore, injected bundles maintained at the injected locations whereas injected free cells were sparsely observed at the injected locations. The second construct was tubular cell carriers generated by self-rolling bilayer films. Active and adhesive layers were consisted of PLGA and poly(D,L lactic acid) (PDLA) films, respectively. Initial strains were applied to the active layer, which folded when the PDLA layer detached on substrates by dewetting under cell culture conditions. Several types of tubes were obtained by initiating the rolling from different directions, which actuated depending on the aspect ratios of the rectangular patterns of bilayer films. After three days incubation of mouse embryonic fibroblasts (MEFs), rat smooth muscle cells (SMCs), and rat endothelial cells (ECs) on the bilayer films, it became tubes with encapsulation of cells.
Bi-min Zhang Newby, Dr. (Advisor)
William M. Chilian, Dr. (Committee Member)
Liya Yin, Dr. (Committee Member)
Ge Zhang, Dr. (Committee Member)
Abraham Joy, Dr. (Committee Member)
Nic D. Leipzig, Dr. (Committee Member)
Cang Cheng, Dr. (Committee Member)
213 p.

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Citations

  • Song, H. (2014). Fabrication of Injectable Cell Carriers Based on Polymer Thin Film Dewetting [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1417442785

    APA Style (7th edition)

  • Song, Hokyung. Fabrication of Injectable Cell Carriers Based on Polymer Thin Film Dewetting . 2014. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1417442785.

    MLA Style (8th edition)

  • Song, Hokyung. "Fabrication of Injectable Cell Carriers Based on Polymer Thin Film Dewetting ." Doctoral dissertation, University of Akron, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=akron1417442785

    Chicago Manual of Style (17th edition)