Regenerative medicine is an exciting research area that aims to generate biological alternatives to harvested tissues or prosthetic implants. Scaffolds (synthetic extracellular-matrices) provide three-dimensional environments for cells and the templates for tissue regeneration. This lecture will focus on design principles scaffolds. The lecture will emphosize the biomimetic strategy. In this approach, the scaffolds mimic advantageous characteristics of the natural extracellular matrix, or developmental and wound healing programs. We design advanced synthetic biomaterials by mimicking certain nanostructures of natural extracellular matrix. We also design novel polymers and self-assembled nanospheres for controlled biomolecule delivery in the scaffolds to recapitulate certain developmental or wound healing programs. We also integrate designed porous network to facilitate tissue regeneration. Enhanced cellular/tissue function and regenerative outcomes of these approaches will be discussed to demonstrate the excitement of the biomimetic approach in scaffold design and biologic delivery.