In nature, cells reside within an extracellular matrix (ECM), consisting of 3-dimensional (3D) networks of collagen and elastin which provide biophysical/chemical signals to direct cellular development and behaviour. Traditional methods of studying cellular behaviour often involve using 2-dimensional in vitro models that are convenient and cost-effective, but may not be representative of 3D in vivo conditions. A synthetic polyampholyte system, poly(N-(3-aminopropyl)methacrylamide hydrochloride-co-acrylic acid) [p(APM-co-AA)], was used here for the first time to construct two types of 3-dimensionally structured cell supports to mimic the ECM: microstructured films and nanofibrous scaffolds. Microstructured films were fabricated using a shape-memory polymer structuring approach and nanofibrous scaffolds were formed using electrospinning. Both films and nanofibers were thermally crosslinked by reaction of initially formed anhydride groups with pendant amines. Film topography was tuned through polymer solution concentration, and the surface chemistry of the crosslinked p(APM-co-AA) scaffolds was tuned by reaction of residual anhydride groups with hydrophilic or hydrophobic amines. The effects of film surface topography and surface chemistry on fibroblast morphologies were explored using fluorescence microscopy. This work presents the fabrication and characterization of tunable, self-crosslinking p(APM-co-AA) scaffolds as promising ECM mimics. / Thesis / Master of Science (MSc) / The extracellular matrix (ECM), present within all biological tissues, consists of 3-dimensional (3D) networks of proteins which provide chemical and physical cues for cells. Abnormalities in the ECM is associated with a variety of disorders, such as coronary heart disease and tumours. Thus, the study of the ECM and how it affects cell behaviour is important both for a better understanding of ECM-related diseases, as well as for creating ECM-mimics for tissue engineering. The goal of this thesis is to explore the fabrication of 3D scaffolds using a synthetic polyampholyte that can be crosslinked under heat and chemically tuned using functionalization. This polyampholyte was electrospun into nanofibers and prepared into microstructured films, which were used to study the effects of surface topography and chemistry on murine fibroblast morphology and attachment. These polyampholyte scaffolds provide a new means to study cell behaviour in environments that mimic certain aspects of the ECM.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22249 |
| Date | 17 November 2017 |
| Creators | Zhou, Christal |
| Contributors | Moran-Mirabal, Jose, Stöver, Harald, Chemistry and Chemical Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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