Desirable cytocompatibility properties of nano-sized ceramics were combined with the tunable degradability and deformability of a select polymer (poly-lactide-co-glycolide, or PLGA) to optimize biological and mechanical properties for orthopedic tissue regeneration. Nanophase ceramics mimic the size scale of constituent components of natural bone and enhance the adsorption of proteins that mediate bone cell adhesion. Results have shown significantly promoted osteoblast (bone-forming cell) adhesion and long-term functions (alkaline phosphatase activity and calcium deposition) on nanophase ceramics compared to conventional (micron-scale) ceramics. Therefore, nano-titania particles were first dispersed in a model polymer (PLGA) matrix using sonication to imitate the nano-sized surface features and distribution of nano-ceramics in/on bone. Surface characteristics of the composites (such as topography, surface area and surface roughness) were studied. Importantly, results showed that osteoblast adhesion was the greatest when surface roughness values of the composites were closer to that of natural bone; this was mediated by controlling the dispersion of titania in PLGA. Moreover, this study demonstrated that the dispersion of nanophase titania in PLGA decreased the harmful acidic pH changes of PLGA as it degrades. From the perspective of mechanical properties, compared to agglomerated nano-titania in PLGA, well-dispersed nanophase titania in PLGA improved the tensile and compressive moduli and strength of these composites. In order to mimic the hierarchical structure of bone, a novel aerosol-based 3D printing technique was used to further fabricate nanostructured 3D ceramic/polymer composites. Osteoblast interactions with these 3D scaffolds provided evidence of an even further promoted bone cell infiltration into such 3D structures. Lastly, nanocomposites were used as novel drug delivery systems to promote bone growth. Specifically, a bone morphogenetic protein (BMP-7) derived peptide (DIF-7c) was loaded onto nanophase hydroxyapatite/PLGA composites by either covalent chemical attachment or physical adsorption. Results demonstrated that the model peptide was successfully immobilized onto nano-HA/PLGA composites using aminosilane chemistry. Moreover, a greater prolonged two-phase release profile was achieved using these nanocomposite-based drug delivery systems over single-phase (hydroxyapatite or PLGA) drug carriers. In summary, this dissertation demonstrated for the first time that nanophase ceramic/polymer composites are promising candidates as novel, drug-carrying orthopedic materials for more effective bone regeneration and bone disease treatment.