Steering Stem Cell Fate within 3D Living Composite Tissues Using Stimuli‐Responsive Cell‐Adhesive Micromaterials

• DOI: 10.1002/advs.202205487
• Publication Date: 2023-01-05T02:11:47Z
• Authors: Tom Kamperman; Niels G. A. Willemen; Cindy Kelder; Michelle Koerselman; Malin Becker; Luanda Lins; Castro Johnbosco; Marcel Karperien; Jeroen Leijten
• Keywords: Spheroid; Cell type

Abstract Engineered living microtissues such as cellular spheroids and organoids have enormous potential for the study regeneration of tissues organs. Microtissues are typically engineered via self‐assembly adherent cells into spheroids, which characterized by little to no cell–material interactions. Consequently, 3D microtissue models currently lack structural biomechanical biochemical control over their internal microenvironment resulting in suboptimal functional performance limited stem cell differentiation potential. Here, this work report on stimuli‐responsive cell‐adhesive micromaterials (SCMs) that can self‐assemble with composite through integrin binding, even under serum‐free conditions. It is demonstrated SCMs homogeneously distribute within act biomechanically biochemically tunable designer materials alter tissue demand. Specifically, behavior controlled based size, stiffness, number ratio, biofunctionalization a temporal manner orthogonal secondary crosslinking strategies. Photo‐based mechanical tuning reveals early onset stiffness‐controlled lineage commitment differentiating spheroids. In contrast conventional encapsulation bulk hydrogel, incorporating cell‐sized uniquely provides cues throughout microtissues’ volume, be essential osteogenic differentiation.