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Extensive research for biomaterial development and implant technology has focused on the surface of the material used because of the influence the surface has on cellular and tissue response. The events at the tissue-implant interface are known to be altered by physical or chemical modifications to the surface of an implant. Due to advances in nanotechology, there is particular interest in materials and processing techniques that can be engineered to elicit specific biological responses. Electrochemical anodization is a nano-fabrication technique that enables precise nano-structures to be formed on the surface of titanium. The vertically aligned, laterally spaced titanium oxide (TiO2) nanotube arrays that are formed via the electrochemical anodization process allow for controlled nano-geometries to be studied. The advantages of the nanotube structure has be previously been demonstrated to significantly accelerate osteoblast cell growth [1], improve bone-forming functionality [2], and direct mesenchymal stem cell fate [3]. These findings raise questions such as : (i) the optimization of the outer limits of the nano-geometry, (ii) the application of a similar nano-architecture to different materials without such properties, and (iii) the effects of nano-structures in vivo. This work investigated the cell response of nanotube structures that were larger than previously researched, as well as the use of a nanotube structure thin film on the surface of polymer for additional orthopedic applications. In addition, this dissertation investigated in vivo bone tissue response to nano-modified implant surface modifications. In order to examine the bone response the structure and chemistry of the nanotube surface to were modified to distinguish adhesion to bone. It was found the increased bone adhesion observed on the TiO2 nanotube surfaces is dependent on both the nanotube structure and chemistry. These findings may be significant for understanding the interaction between bone tissue and implant surfaces. The understanding of tissue and cell response to surface geometry and chemistry is critical to advance the field of orthopedic surface technology, and to further the understanding of cellular interactions with complex nano-interfaces