Cell migration on planar and three-dimensional matrices: a hydrogel-based perspective

The migration of cells is a complex process that is dependent on the properties of the surrounding environment. In vivo, the extracellular environment is complex with a wide range of physical features, topographies, and protein compositions. There have been a number of approaches to design substrates that can recapitulate the complex architecture in vivo. Two-dimensional (2D) substrates have been widely used to study the effect of material properties on cell migration. However, such substrates do not capture the intricate structure of the extracellular environment. Recent advances in hydrogel assembly and patterning techniques have enabled the design of new three-dimensional (3D) scaffolds and microenvironments. Investigations conducted on these matrices provide growing evidence that several established migratory trends obtained from studies on 2D substrates could be significantly different when conducted in a 3D environment. Since cell migration is closely linked to a wide range of physiological functions, there is a critical need to examine migratory trends on 3D matrices. In this review, our goal is to highlight recent experimental studies on cell migration within engineered 3D hydrogel environments and how they differ from planar substrates. We provide a detailed examination of the changes in cellular characteristics such as morphology, speed, directionality, and protein expression in 3D hydrogel environments. This growing field of research will have a significant impact on tissue engineering, regenerative medicine, and in the design of biomaterials.