AbstractTissue engineering aims at resolving problems such as donor shortage and immune rejection faced by transplantation. Scaffolds (artificial extracellular matrices) have critical roles in tissue engineering. Recently, we developed nano‐fibrous poly(L‐lactic acid) 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 four 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 poly(L‐lactic acid) material. Furthermore, nano‐fibrous scaffolds also allowed >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. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 531–537, 2003