Infection of a transcutaneous orthopedic prosthesis is undesirable and decreases the success rate of an implant. Critical to reducing this infection is to develop materials that can decrease bacteria colonization and/or increase skin growth. Since previous studies have demonstrated significantly less bacteria colonization (yet promoted osteoblast, bone forming cell, functions) on titanium (Ti) with select nanofeatures, the objective of this in vitro study was to determine keratinocyte (skin forming cells) functions on Ti modified to have nanoscale surface features. To further promote keratinocyte functions, some Ti surfaces were functionalized with fibroblast growth factor-2 (FGF-2). Nanometer-sized topographical surface features were created on traditional Ti implants by anodization (termed nanotubular) and electron beam evaporation (termed nanorough). This study found that compared to conventional (nanosmooth) Ti, the nanotubular and nanorough Ti surfaces promoted keratinocyte density. Moreover, when functionalized with FGF-2, keratinocyte density increased on all surfaces, resulting in the greatest keratinocyte density on nanorough and nanotubular Ti-functionalized with FGF-2 after 5 days of culture. Interestingly, keratinocyte densities on nanorough and nanotubular Ti were similar to that achieved on conventional Ti functionalized with FGF-2. Therefore, when considered in the context of other studies, the results of this in vitro study demonstrated that certain nanometer-sized Ti topographies may be useful for increasing keratinocyte density while reducing bacteria adhesion and promoting bone tissue formation and, thus, should be further studied for improving the efficacy of various transcutaneous Ti-based orthopedic implants. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2011.