The complex mechanisms of the bone cell-surface interactions are yet to be completely understood, and researchers continue to strive to uncover the fully optimized implant material for perfect osseointegration. A particularly fascinating area of research involves the study of nanostructured surfaces, which are believed to enhance osteogenic behavior, possibly due to the mimicry of components of the extracellular matrix of bone. There is a growing body of data that emphasizes the promise of the titanium oxide (TiO2) nanotube architecture as an advanced orthopedic implant material. The review herein highlights findings regarding TiO2 nanotube surfaces for bone regeneration and the osteogenic effects of minute changes to the surface such as tube size and surface chemistry. 1. Characteristics and Function of Normal Bone Bone is a complex tissue that has the ability to heal and regenerate itself [1], and is continuously in the cycle of remodeling from before birth until death [2]. The process of bone modeling and remodeling typically occurs to help the bone adapt to mechanical forces or to replace microdamaged bone with new, stronger bone [2]. Occasionally bone defects will form that are unable to heal on their own, either due to bone disease or trauma. In these cases, bone reconstruction is necessary, which requires osteoproduction (colonization of osteogenic stem cells at defect site), osteoinduction (induced bone formation), osteoconduction (growth of bone on a surface), osseointegration (stable anchorage of an implant achieved by direct bone-to-implant contact), mechanical stimulation, and vascularization [1, 3, 4]. In many cases an orthopedic implant is needed in order to stabilize the defect and provide support for new bone to grow. In order for orthopedic surgery to be successful, a strong and lasting connection between the implant and the interfacing bone tissue must be quickly established. A large part of current orthopedics research is centered on designing the material surface to more readily recruit bone forming cells to that interface. 2. The Evolution of Biomedical Materials Technology The technology and design of materials for bone implants have evolved tremendously over the past 50 years, through what Hench and Polak defines as three generations of biomedical materials [5]. First-generation biomedical materials (of the 60s and 70s) were designed solely to “achieve a suitable combination of physical properties to match those of the replaced tissue with a minimal toxic response in the host” [5]. In the late 70s to early 80s, the focus of
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