Ceramic/polymer nanocomposites simulate bone much closer in terms of its nanostructure and associated properties, thus, offering a promising opportunity for bone regeneration in a natural way. Previous studies demonstrated improved osteoblast (bone-forming cell) adhesion and long-term functions (such as alkaline phosphatase activity and calcium-containing mineral deposition) on nanometer scale surface roughness provided by well-dispersed titania nanoparticles in poly-lactide-co-glycolide (PLGA). For example, the nanocomposites with the closest surface roughness to natural bone at the nano-scale promoted the most bone cell adhesion and calcium deposition. The current studies focus on further mimicking bone by building three-dimensional structures from titania/PLGA nanocomposites using a novel aerosol based 3D printing technique (one type of rapid prototyping technique, because, similarly, natural bone assembles its three-dimensional hierarchical architecture from nanostructured building blocks). Using this technique, bone fracture data acquired by computed tomography (CT) can be transferred into CAD models and used to direct the fabrication of versatile bone substitutes. Field emission scanning electron microscopy (FESEM) was used to characterize the structure and surface features of these 3D scaffolds. The results demonstrated that 3D printed nano-scaffolds had a well-controlled, repeatable inner structure and, moreover, possessed uniformly dispersed titania nanoparticles which provided for nano-scale surface features throughout the PLGA matrix. Osteoblast adhesion tests were conducted on the 3D titania/PLGA nanocomposite scaffolds created by this technique and the results demonstrated that these 3D scaffolds further promoted osteoblast infiltration into porous structures compared to previous nanostructured surfaces. In conclusion, results of this study have evaluated a promising new orthopedic nanocomposite and a means of fabricating a hierarchical macro-structure from such nanomaterials that can mimic properties of natural bone, thus, providing a new material and approach for more effective orthopedic applications.