Circular Patterns of Dynamic Covalent Hydrogels with Gradient Stiffness for Screening of the Stem Cell Microenvironment

As extracellular matrix (ECM) mimetic materials, hydrogels have been widely used for broad biomedical applications. However, with so many physical or chemical cues in the matrix that regulate cell behaviors or functions, it remains challenging to design a customizable hydrogel with the desired properties on demand. In the current study, we aim to establish a circular-patterned hydrogel model with gradient stiffness for screening the most favorable ECM environment for specific cells or certain application purposes. First, six types of hydrogels with a wide stiffness range of 1.2-28.9 kPa were prepared by dynamic covalent cross-linking between gelatin derivatives and oxidized hyaluronic acid. Taking advantage of their instantaneous self-healing property from dynamic chemistry, the hydrogels were further spliced into one whole piece of circular-patterned hydrogel. When rabbit bone marrow mesenchymal stem cells were seeded in the center, the influences of matrix stiffness on the regulation of stem cell adhesion, migration, and differentiation were directly observed and compared under one visual field. In addition, these hydrogels all possessed good biocompatibility, degradability, and injectability, showing great potential for tissue-engineering-related applications.