Tissue engineering aims at resolving problems such as donor shortage and immune rejection faced in transplantation. Scaffolds (artificial extracellular matrices) play critical roles in tissue engineering. Recently, we developed nano-fibrous poly(L-lactic acid) (PLLA) scaffolds under the hypothesis that synthetic nano-fibrous scaffolding, mimicking the structure of natural collagen fibers, could create a more favorable microenvironment for cells. This is the first report that the nano-fibrous architecture built in three-dimensional scaffolds improved the features of protein adsorption, which mediates cell interactions with scaffolds. Scaffolds with nano-fibrous pore walls adsorbed 4 times more serum proteins than scaffolds with solid pore walls. More interestingly, the nano-fibrous architecture selectively enhanced protein adsorption including fibronectin and vitronectin, even though both scaffolds were made from the same PLLA material. Furthermore, nano-fibrous scaffolds also allowed more than 1.7 times of osteoblastic cell attachment than scaffolds with “solid” pore walls. These results demonstrate that the biomimetic nano-fibrous architecture serves as superior scaffolding for tissue engineering.