UC San Diego

Interactions of cells with their extracellular matrix (ECM) play an important role in development, disease progression, and regeneration. The material properties of ECM such as geometry, chemistry, hydrophobicity, mechanics, and microstructure play an important role in regulating various cellular processes and tissue morphogenesis. Thus there is a surge of interest in determining the effect of various material properties on cell fate and tissue formation. Beyond providing fundamental understandings, these efforts can also led to development of effective scaffolds (structural support for cell culture) as scaffold engineering is an integral part of in vitro cell cultures, tissue engineering, and transplants/implants. The central focus of this thesis is design of polymer- based biomaterials as synthetic matrices for cell culture and understands how cell-matrix interactions affect tissue formation, stem cell differentiation and self-renewal. The first two chapters focuses on synthesis and characterization of three dimensional hydrogels having interconnected macroporous network structures of poly(ethylene glycol) using cryogelation techniques, where I have developed a novel, green strategy to create monolithic structures with heterogeneous and homogenous networks. I have also developed a process to create three- dimensional structures with different internal architecture while maintaining the same porosity. These 3D structures were then used to understand effect of scaffold porosity, pore structure, etc play an important role in cell proliferation, differentiation, and tissue formation using cartilage tissue engineering as a model system. We also harnessed the potential of cell-matrix interactions to develop defined, synthetic matrices to expand human embryonic stem cells in vitro without introducing any detrimental effects. Employing a number of hydrogels I have determined the effect of various physico-chemical cues (bulk and interfacial properties) on adhesion, growth, colony formation, and self-renewal of human embryonic stem cells. Poly[acrylamide-co-sodium 4-vinylbenzenesulfonate] hydrogels having a moderate hydrophobicity (water contact angle of 23°) and bulk rigidity of 343.7kPa have supported in vitro growth of a number of hPSCs (HUES9, HUES6, and iPSCs) in defined medium (StemPro®) for more than 20 passages. These studies are discussed in chapter 4