Steering Stem Cell Fate within 3D Living Composite Tissues Using Stimuli‐Responsive Cell‐Adhesive Micromaterials. Issue 10 (4th January 2023)

• Record Type: Journal Article
• Authors: Kamperman, Tom; Willemen, Niels G. A.; Kelder, Cindy; Koerselman, Michelle; Becker, Malin; Lins, Luanda; Johnbosco, Castro; Karperien, Marcel; Leijten, Jeroen
• Is Part Of: Advanced science. Volume 10:Issue 10(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-01-04
• Subjects: 3D cell culture -- cell–matrix interactions -- microgels -- smart materials -- tissue engineering; Science -- Periodicals; 505
• DOI: 10.1002/advs.202205487
• Languages: English
• ISSNs: 2198-3844

Abstract

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