Hydrogel Scaffolds with Controlled Postgelation Modulation of Structures for 3D Cell Culture and Tissue Engineering

Hydrogels are hydrophilic three-dimensional networks containing a large amount of water, with physicochemical properties similar to extracellular matrix and controlled mechanical strength, making them ideal scaffolds for 3D cell culture and tissue engineering. However, the cross-linked hydrogel network often restricts the migration of cells and the exchange of nutrients, which affects cell proliferation and the development of normal tissues. In recent years, hydrogels with pore-channel structures have attracted significant attention, but these spatial structures are usually preconstructed before gelation, posing challenges in meeting the dynamic physiological conditions required during cell and tissue growth. Therefore, considerable efforts have been devoted to structurally regulate the scaffolds after gelation, so as to enhance the interactions between the scaffolds and cells for promoting the growth of cells and tissues. This review firstly outlines the preparation of hydrogel scaffolds with pore structure and the necessity of postgelation pore modulation. Two types of methods for postgelation pore modulation, including chemical degradation and physical dissolution, are then summarized. Finally, the potential application of such postgelation structural modulation in 3D cell culture and tissue engineering is discussed. Various methods of structural modulation of hydrogels after gelation are emphasized here. The figure illustrates the process of internal structural changes in a hydrogel after different stimulations. These methods enable the fabrication of pore size structures within hydrogels. This hydrogel scaffold has potential applications in 3D cell culture and tissue engineering.image