With the ability to form nano-fibrous structures, a drive to mimic the extracellular matrix (ECM) and form scaffolds that are an artificial extracellular matrix suitable for tissue formation has begun. These nano-fibrous scaffolds attempt to mimic collagen, a natural extracellular matrix component, and could potentially provide a better environment for tissue formation in tissue engineering systems. Three different approaches toward the formation of nano-fibrous materials have emerged: self-assembly, electrospinning and phase separation. Each of these approaches is very different and has a unique set of characteristics, which lends to its development as a scaffolding system. For instance, self-assembly can generate small diameter nano-fibers in the lowest end of the range of natural extracellular matrix collagen, while electrospinning has only generated large diameter nano-fibers on the upper end of the range of natural extracellular matrix collagen. Phase separation, on the other hand, has generated nano-fibers in the same range as natural extracellular matrix collagen and allows for the design of macropore structures. These attempts at an artificial extracellular matrix have the potential to accommodate cells and guide their growth and subsequent tissue regeneration.