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

Doctor of Philosophy, Case Western Reserve University, 2015, Biomedical Engineering

The growing socioeconomic burden of musculoskeletal injuries resulting in critical-sized bone defects and drawbacks of current therapies have motivated tissue engineering approaches to generate functional tissues to repair bone. This dissertation aimed to develop a readily implantable system to heal bone defects through investigation of the hypothesis that controlled presentation of inductive factors from microparticles to mesenchymal stem cells (MSCs) in high-density culture can guide endochondral bone formation. First, a cartilage template for endochondral ossification was engineered by incorporating TGF-β1-releasing gelatin microparticles (GM) within MSC aggregates and self-assembled sheets. TGF-β1 presentation from GM is predominantly through cell-mediated microparticle degradation with rates tunable by varying polymer crosslinking. Chondrogenesis was shown to be dependent on TGF-β1 concentration and GM amount. Since hydroxyapatite and BMP-2 can regulate chondrogenesis and osteogenesis, their effects on endochondral ossification within MSC aggregates were investigated. Hydroxyapatite was presented in the form of mineral-coated hydroxyapatite microparticles (MCM) capable of controlled BMP-2 delivery. Alone, BMP-2 and MCM induced osteogenesis and chondrogenesis, respectively. Together, BMP-2 and MCM promoted early chondrogenesis followed by additional mineralization, suggesting the induction of endochondral ossification. MSC aggregates were also locally presented with TGF-β1 and BMP-2 by tailoring GM to release the former early for chondrogenic induction and MCM to deliver the latter in a more sustained manner to promote the replacement with bone. Compared to media supplementation, local delivery of TGF-β1 and BMP-2 promoted enhanced chondrogenesis and ALP activity at week 2 and stronger mineralization by week 5. Compared to TGF-β1 or BMP-2 alone, combined treatment resulted in larger mineralized constructs with higher DNA and GAG/DNA content. The ability of thi (open full item for complete abstract)

Committee: Eben Alsberg (Advisor) Subjects: Biomedical Engineering