Stem cell-based regenerative medicine aims to repair and regenerate injured and/or diseased tissues by implanting a combination of cells, biomaterials, and soluble factors. Unfortunately, due to an incomplete understanding and knowledge of the interactions between biomaterials and specific stem cell types, and the inability to control the complex signaling pathways ensured by these interactions, the ability to design functional tissue and organ substitutes has been limited. The greatest challenge remains the ability to control stem cells' fate outside of the cell's natural microenvironment or "niche". Stem cell fate is known to be regulated by signals from the microenvironment, such as extracellular matrix (ECM) including glycosaminoglycans and proteoglycans to which stem cells adhere. They represent an essential player in stem cell microenvironment because they can directly or indirectly modulate the maintenance, proliferation, self-renewal, and differentiation of stem cells. The interactions between stem cells and the ECM play a critical role in living tissue development, repair, and regeneration as well. The design of artificial ECM and/or binding site is important in tissue engineering because artificial ECM and/or binding regulates cellular behaviors. Identification of binding sites and key motifs in ECM proteins that interact with cellular receptors can allow researchers to generate small peptides that can mimic the function of large ECM proteins.