The ability to mimic the chemical, physical and mechanical properties of the natural extra-cellular matrix is a key requirement for tissue engineering scaffolds to be successful. In this study, we successfully fabricated aligned nanofibrous multi-component scaffolds for bone tissue engineering using electrospinning. The chemical features were mimicked by using the natural components of bone: collagen and nano-hydroxyapatite along with poly[(D,L-lactide)-co-glycolide] as the major component. Anisotropic features were mimicked by aligning the nanofibers using a rotating mandrel collector. We evaluated the effect of incorporation of nano-HA particles to the system. Themorphology and mechanical properties revealed that,at lowconcentrations, nano-HA acted as a reinforcement. However, at higher nano-HA loadings, it was difficult to disrupt aggregations and, hence, a detrimental effect was observed on the overall scaffold properties. Thermal analysis showed that there were slight interactions between the individual components even though the polymers existed as a two-phase system. Preliminary in vitro cell-culture studies revealed that the scaffold supported cell adhesion and spreading. The cells assumed a highly aligned morphology along the direction of fiber orientation. Protein adsorption experiments revealed that the synergistic effect of increased surface area and the presence of nano-HA in the polymer matrix enhanced total protein adsorption. Crosslinking with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride resulted in improved mechanical properties of the scaffolds and improved degradation stability, under physiological conditions. (Figure Presented) © 2010 WILEY-VCH Verlag GmbH & Co. KGaA.