In designing scaffolds for tissue regeneration, the principal objective is to recapitulate extracellular matrix (ECM) function in a temporally coordinated and spatially organised structure. A key issue is to encode required biological signals within the scaffold so that all aspects of cell response-adhesion and migration, proliferation and phenotype choice-can be controlled. In achieving this objective nanotechnology, bottom-up design approach and solid free-form fabrication (SFF) will play key roles, along with self-assembly processes. For scaffold materials, there must be the correct balance between architectural features notably, porosity and chemical, physical and biological properties. This paper reviews the main achievements in biomaterials design and the future challenges.