| This dissertation describes the use of engineered, nanoscale materials for human repair. Three different systems are discussed, one based on inorganic coatings for titanium substrates to be used for bone regeneration, and two based on self-assembling peptide amphiphile nanofibers that resemble the extra-cellular matrix. By controlling the chemistry and materials properties of the materials, specific cellular responses can be observed.; Organoapatite, a ceramic material containing hydroxyapatite, the mineral from which bone and teeth are make, and a small amount of poly(amino acids) has been chemically modified to adsorb zinc ions onto its surface. Zinc is an essential trace element found in bone and can stimulate biomineralization both in vitro and in vivo. When coated onto a titanium substrate via an electrostatic pretreatment, the new material, zinc-containing organoapatite (ZnOA), forms a porous, nanocrystalline material capable of delivering zinc ions to cells for biomineralization. In vitro studies of osteoblastic cells cultured on ZnOA coated titanium meshes in a rotating bioreactor show that ZnOA coatings promote the earlier onset of alkaline phosphatase (ALP) activity and the production of mineralized bone nodules as compared to controls.; Peptide amphiphile (PA) molecules containing a hydrophilic bioactive peptide head-group coupled to a hydrophobic alkyl tail that self-assemble to form nanofibers displaying the peptide head-group on the fiber have been studied as artificial extra cellular matrices. In one series of studies, the integrin-based adhesion of fibroblastic cells and the migration of highly invasive breast cancer cells on PA nanofibers containing the cell adhesion sequence RGDS was shown to be dependent on the architecture of the PA molecule. In another series of studies, PA's designed to mimic the active site of ALP displayed metal-dependent self-assembly, as well as specific binding of zinc ions to histidine residues in the PA and promoted the proliferation and biomineralization of osteoblastic cells. |
