Nanostructured Materials as Molecular Transporters and Cell Growth Substrates For Drug Delivery and Tissue Engineering Applications.

Carbon nanotubes (CNTs) are increasingly finding applications in many fields such as tough composites, electronics, and biomedicine, due to their outstanding properties. In terms of biomedical applications, CNTs can be used as cellular growth scaffolds which mimic the structural design of tissue at the nanoscale. This is for tissue engineering applications. CNTs are also being used as cellular transporters of biomolecules or drugs for controlled drug delivery to cells. This thesis reports the use of functionalized CNTs for delivery of peptides into cells, and studies of CNT assemblies-based tissue engineering scaffolds. The uptake into mammalian cells of CNTs both with and without designed peptide was studied in Chinese Hamster Ovary (CHO) cells. Cells were incubated with CNTs and the uptake mechanism, translocation, and their potential toxicity are studied. The CNT-peptide composites were found to be readily taken up but they did not reach the cytoplasm, instead they were restricted to endosomes and lysosomes. The exploration of CNT assemblies as cell growth substrates and the effects of substrate topography on cell adhesion and function was carried out using human hepatoma (Huh7) and CHO cells, and primary liver cells (rat hepatocytes). The results with perhaps the greatest potential are those for the primary liver cells, particularly for liver-tissue engineering for applications in drug discovery where liver cells growing on CNT-based substrates could serve as an in vitro liver model for screening for liver toxicity. In vivo, the environment of cells is 3D and this thesis contains preliminary results on cells including primary liver cells growing on 3D CNT-based yam substrates. In this thesis the challenges associated with evaluation of the toxicity of CNTs are discussed too. In addition, CHO cell adhesion and growth on protein fibronectin-nanopatterned substrates prepared using block-copolymer surfaces are also evaluated