MS, University of Cincinnati, 2016, Engineering and Applied Science: Biomedical Engineering

Chronic ulcers are a major complication in patients suffering from diabetes mellitus, and standard treatment and management procedures often fail to realize complete and timely healing of these wounds as they do not address pathophysiological complexities of the disease. This brings an urgent need for new, effective therapeutic modalities to replace existing methods. Cell sheet engineering generates viable and functionally active cell sheets using thermoresponsive culture surfaces and a potential application would be in accelerating healing of chronic diabetic ulcers by grafting a monolayer of epidermal cell onto wound site for coverage after routine treatment. This is achievable using PNIPAAm-based, thermoresponsive cell culture surfaces. In this study, we fabricate thermoresponsive PNIPAAm/collagen substrates in order to assess the responses of keratinocytes cultured on these substrates with respect to adhesion, proliferation and apoptosis.

Committee: Daria Narmoneva Ph.D. (Committee Chair); T. Douglas Mast Ph.D. (Committee Member); Marepalli Rao Ph.D. (Committee Member) Subjects: Biomedical Research

Master of Science, University of Akron, 2016, Chemical Engineering

Poly (N-isopropylacrylamide) (pNIPAAm), a thermo-responsive polymer that exhibits a lower critical solution temperature (LCST) of 32 °C in water has found an extensive use in tissue engineering and bioengineering applications in general. Since it is soluble in water, one of the main challenges that limit its applications in an aqueous environment is the tedious and expensive electron beam or plasma based procedures to retain it on a substrate. In this study, we report the use of various types of organosilanes to form siloxane networks for immobilizing pNIPAAm onto Si-wafer and silica glass substrates in a simple two-step approach: spin coating followed by thermal curing. Attempts are made to elucidate the entrapment mechanism and factors that affect such entrapment. It was found that the entrapment occurs via the segregation of high surface tension organosilanes towards the substrate at a temperature higher than the glass transition temperature (Tg) of pNIPAAm and simultaneous cross-linking of the segregated organosilane molecules that form siloxane networks. Organosilanes having low surface tension were found to segregate towards the air-film interface leading to poor entrapment. Factors such as polarity and hydrogen bonding were found to influence the retention of those organosilanes in the blend film during spin-coating and thermal annealing and subsequent film retention after 3 days of soaking in cold water. Additionally, organosilanes that are allowed to hydrolyze and oligomerize in the blend solution prior to spin-coating also resulted in higher organosilane retention and subsequently, thicker retained blend films compared to solutions that were spin-coated immediately after preparation. Substrates utilizing those organosilanes to entrap pNIPAAm resulted in stable films that exhibited thermo-responsive behaviors that were verified by wettability measurements. Rapid cell sheet detachment (<5 min) of embryonic mouse fibroblast cells were obtained on all su (open full item for complete abstract)

Committee: Bi-min Zhang Newby Dr. (Advisor); Gang Cheng Dr. (Committee Member); Jie Zheng Dr. (Committee Member) Subjects: Biomedical Research; Chemical Engineering; Chemistry; Materials Science; Polymers

MS, University of Cincinnati, 2014, Engineering and Applied Science: Biomedical Engineering

Poly (N-isopropylacrylamide) (PNIPAAm) is a well-known thermo-responsive polymer that has be shown to be biocompatible, with surfaces coated with PNIPAAm supporting the culture of cells. These surfaces support the adhesion and proliferation of multiple cell phenotypes at 37 °C, when surface is hydrophobic, as the polymer chains are collapse and lose their affinity for water. Reducing the temperature below the polymers lower critical solution temperature (LCST) elicits hydration and swelling of the polymer chains and leads to cell detachment. In vitro culture on thermo-responsive surfaces can be used to produce cell sheets for the use of different therapeutic treatments. PNIPAAm coated membranes were used to culture human keratinocyte cells to confluence, with cell release possible after exposing the membranes to room temperature (25 °C) for 10 minutes. Cell sheet transfer was possible from the coated membrane to cell culture dishes using a protocol that we developed. There was also a trend towards similar cell apoptosis on both PNIPAAm coated and uncoated surfaces.

Committee: Daria Narmoneva Ph.D. (Committee Chair); T. Douglas Mast Ph.D. (Committee Member); Dale Schaefer Ph.D. (Committee Member) Subjects: Biomedical Research

Doctor of Philosophy, University of Akron, 2014, Biomedical Engineering

A modular approach to create organized tissue that has gained much attention since the introduction of thermoresponsive surfaces is the assembly of cell sheets. With a change in temperature of grafted poly-N-isopropylacrylamide (pNIPAAm), a thermoresponsive polymer, cell sheets can be harvested with their deposited extracellular matrix (ECM) intact. PNIPAAm has been covalently grafted to cell culture substrates by two primary methods: electron beam irradiation and plasma polymerization. Most tissue engineering laboratories have difficulties using these approaches to custom-make their thermoresponsive surface for specific applications due to the complexities of associated procedures and limited access to required equipment (e.g. e-beam). The goal of this study was to develop a simple, cost-effective approach for the creation of thermoresponsive surfaces using commercially available pNIPAAm for cell sheet harvest. Methods to effectively manipulate viable cell sheets (e.g. transfer and stack) were developed. In addition, a study of cell sheet interaction on fibrin gels is presented and analyzed for future cardiac tissue engineering applications.

Committee: Ge Zhang Dr. (Advisor); Bi-min Zhang Newby Dr. (Advisor); Rebecca Willits Dr. (Committee Member); Bing Yu Dr. (Committee Member); Richard Londraville Dr. (Committee Member) Subjects: Biomedical Engineering; Biomedical Research

Doctor of Philosophy, Case Western Reserve University, 2006, Macromolecular Science

High performance in polymer blends and composites can be achieved through the addition of a strong filler component into a polymer matrix. The overall physical and chemical properties of a composite are determined in large part by the interaction of this filler component with the matrix.Low density polymer composites have been prepared using clay aerogels. The structure of clay aerogels can be modified by varying either the process conditions or by electrolyte addition during its preparation. By such process changes, the overall structure and density of the resulting composites can be controlled. Clay aerogel imparts thermal, mechanical and structural stability to the composites. Enhanced oxygen barrier (~3X) in blends was achieved by addition of kinked molecule of poly(m-xylylene adipamide) MXD6 into a poly(ethylene terephthalate), PET, matrix. The resulting blend is optimized for its optical and chemical properties. Transparency of these blends was improved by reducing the refractive index mismatch in the stretch direction through the addition of high refractive index co-polyamides. PET, when melt processed with MXD6 results in a chemical reaction which generates color; the structure of the resulting conjugated chromophore is mechanistically determined through the investigation of model compounds. Color is thus eliminated in the blends by reducing the conjugated chromophore.

Committee: David Schiraldi (Advisor) Subjects: