As soft and wet scaffolds, hydrogels are attractive materials for tissue engineering due to their similarity in structure and properties to living tissue. For designing hydrogels as potential artificial tissues, some basic requirements, such as a high level of cellular viability, suitable viscoelasticity, and high mechanical strength are required. However, it is difficult to develop a hydrogel that satisfies even two of these requirements at the same time. In this review, our recent advances in developing synthetic hydrogels as cell culture scaffold are summarized. We found that endothelial cells (ECs) can proliferate directly on some synthetic hydrogels with negatively charge, so long as the hydrogels have a Zeta potential lower than c.a. -20 mV , and the cell behavior can be controlled by adjusting the hydrogel's charge density. Furthermore, confluent EC monolayers cultured on the hydrogels show excellent platelet compatibility, compared to EC monolayer cultured on polystyrene plate. On the basis of the above study, we have further developed micro-patterned hydrogels for selective cell spreading, proliferation, and orientation. We have also developed tough hydrogels on which cells show viability. These results will promote the potential applications of synthetic hydrogels in tissue engineering.