Composition and Mechanism of Three-Dimensional Hydrogel System in Regulating Stem Cell Fate

Three-dimensional (3D) hydrogel systems integrating different types of stem cells and scaffolding biomaterials have an important application in tissue engineering. The biomimetic hydrogels that pattern cell suspensions within 3D configurations of biomaterial networks allow for the transport of bioactive factors and mimic the stem cell niche in vivo, thereby supporting the proliferation and differentiation of stem cells. The composition of a 3D hydrogel system determines the physical and chemical characteristics that regulate stem cell function through a biological mechanism. Here, we discuss the natural and synthetic hydrogel compositions that have been employed in 3D scaffolding, focusing on their characteristics, fabrication, biocompatibility, and regulatory effects on stem cell proliferation and differentiation. We also discuss the regulatory mechanisms of cell-matrix interaction and cell-cell interaction in stem cell activities in various types of 3D hydrogel systems. Understanding hydrogel compositions and their cellular mechanisms can yield insights into how scaffolding biomaterials and stem cells interact and can lead to the development of novel hydrogel systems of stem cells in tissue engineering and stem cell-based regenerative medicine. Impact statement Three-dimensional hydrogel system of stem cell mimicking the stemcell niche holds significant promise in tissue engineering and regenerative medicine. Exactly how hydrogel composition regulates stem cell fate is not well understood. This review focuses on the composition of hydrogel, and how the hydrogel composition and its properties regulate the stem cell adhesion, growth, and differentiation. We propose that cell-matrix interaction and cell-cell interaction are important regulatory mechanisms in stem cell activities. Our review provides key insights into how the hydrogel composition regulates the stem cell fate, untangling the engineering of three-dimensional hydrogel systems for stem cells.