One important aspect of tissue engineering is the development of new biomaterials to facilitate cell–material interactions, which can be achieved by mimicking certain advantageous features of natural extracellular matrix (ECM). Biomimetic nanoscale materials mimic the natural ECM and can be used as scaffolds to provide a better environment for new tissue formation. This chapter focuses on biomimetic nanoscale materials for tissue engineering. First, several techniques are introduced for the fabrication of nanophase scaffolds, which mimic the physical architecture of natural ECM. Second, the role of surface modification in mimicking the chemical composition of natural ECM is discussed. Two novel surface-modification techniques are presented to illustrate the process of fabricating biomimetic scaffolds that mimic both the physical architecture and chemical composition of natural collagen type I. Finally, the biological effects of the nanoarchitecture of scaffolds, such as protein interaction and cell function, including cell attachment, proliferation, and differentiation, are discussed.