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The relationship between nanoscience and nanotechnology is discussed in this paper. Nanobiotechnology is aimed at the molecular design of interfaces for improved medical devices and diagnostics. Medical device implants, and the biomaterials that comprise them, are measured on macro scales (centimeters). Yet the biocompatibility of such devices may be dictated by phenomena best described at nanometer dimensions. Biological data on the in vivo healing responses of mammals to matricellular proteins such as osteopontin, thrombospondin 2 and SPARC with nonspecific protein adsorption is presented. The method including protein orientation (assembly) and type I collagen used to deliver signals along with their strategies is presented. Modern surface analysis techniques shows the complexity of a functional nanobiointerface.