The chemical, physical, and biological characteristics of natural biopolymers, especially extracellular matrix (ECM) proteins, which are the major functional biopolymers, are discussed. The ability of these biopolymers to guide differentiation of mesenchymal stem cells (MSC) into osteogenic, chondrogenic, adipogenic, cardiomyogenic, and neural cell lineages, is also presented. Recent studies have found that patch sheets of immobilized antibodies or ligands targeting specific stem cells, which recruit the stem cells from the patient's body, are effective in gathering autologous stem cells at sites of injury. Park et al. reported that mechanical strain regulated the expression of vascular smooth muscle cell (SMC) markers in MSCs. Takahashi et al. fabricated biodegradable gelatin sponges incorporating various amounts of (β-tricalcium phosphate (βTCP) (gelatin-(βTCP)263 and investigated the in vitro osteogenic differentiation of MSCs isolated from rat bone marrow. Gil et al. found that the oligodendrocytic differentiation of hESCs was efficiently promoted by vitronectin.