Abstract
The fate of stem cell differentiation is guided by several different factors of the stem cell microenvironment, such as cell culture biomaterial elasticity (physical cues) and cell–biomaterial interactions (biological cues). Mimicking the stem cell microenvironment using polymer hydrogels with optimal elasticities is an excellent strategy for stem cell expansion and differentiation. This chapter describes poly(vinyl alcohol) (PVA) hydrogels grafted with several nanosegments that are designed for the culture and differentiation of human hematopoietic and progenitor cells (hHSPCs), human amniotic fluid stem cells (hAFSCs), and human pluripotent stem cells (hPSCs). The elasticity of the cell culture hydrogels can regulate stem cell adhesion overall, as well as cell phenotype, focal adhesions, and morphology, especially in 2-D culture conditions. The mechano-sensing of cell culture biomaterials by stem cells is typically regulated by integrin-mediated focal adhesion signaling. PVA hydrogels having a storage modulus (E′) of 12–30 kPa were found to be efficient materials for ex vivo hHSPC expansion. We also developed PVA hydrogels grafted with oligopeptides derived from vitronectin (PVA-oligoVN hydrogels), which can be produced to have a variety of stiffnesses, for the xeno-free culture of hPSCs. The ideal stiffness of the PVA-oligoVN hydrogels for hPSC culture was found to be 25.3 kPa. A high concentration of oligoVN (500–1500 µg/mL) should be used to prepare the PVA-oligoVN hydrogels to achieve a sufficient oligoVN surface density to maintain hPSC pluripotency. Optimized stiffness (physical cues) and cell-binding moiety surface density (biological cues) are the key factors for designing hydrogel-based cell culture materials for supporting hPSC pluripotency in xeno-free culture conditions.