| This dissertation covers several aspects of tissue-biomaterial interactions, including protein-surface, protein-protein, and cell-matrix interactions. Better understanding of these interactions is crucial for the development of biomaterials that can turn on specific biological signals.;The ability to control protein orientation will facilitate the effort to develop biomaterials with superior biocompatibility. In this work, the orientation of adsorbed proteins on biomaterials was controlled on charged surfaces. Well controlled carboxylic acid (COOH-) and amine (NH2-) terminated self-assembled monolayers (SAMs) were used to represent negatively and positively charged surfaces, respectively, and mouse monoclonal anti-human chorionic gonadotropin (hCG) was used as a model protein to demonstrate the charge-driven protein orientation principle. A combined technique of time-of-flight secondary ion mass spectrometry (ToF-SIMS) and principal components analysis (PCA) was developed to probe the orientation of adsorbed proteins directly. The charge-driven protein orientation principle was then applied to modulating the adhesion and spreading of endothelial cells by controlling the orientation of cell-adhesive proteins on charged SAMs.;Better understanding of protein-protein interactions within the extracellular matrix (ECM) will provide insight into their signaling roles in normal wound healing and wound healing in the presence of implanted materials. In this work, a binding assay based on a surface plasmon resonance (SPR) sensor was developed for the reliable identification of protein-binding pairs under different physiological conditions. Furthermore, atomic force microscopy (AFM) was applied for the identification of protein-binding sites by directly visualizing binding complexes.;The biochemical and biophysical interactions of cells with matrices will influence the proliferation of cells and their differentiation to various phenotypes or functions. In this work, cell-matrix interactions were controlled by manipulating either the topographic properties of polydimethylsiloxane (PDMS) substrates covered with cell-adhesive proteins or the structures of fibrin bi-layers formed in a stepwise way on surfaces of different chemistries. Distinctive cellular responses, such as cell morphology and capillary differentiation, were observed on these matrices. |
