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Glucose-Responsive Self-Rolling Antioxidant Hydrogel Actuators for a Cell Culture Platform

Zheng Z, Xiao R, Ma X, Yu Z, Zeng J, Liao L

ACS applied materials & interfaces, 2025

Abstract

Three-dimensional (3D) cell culture technology can mimic the physiological characteristics of tissues and organs, making it highly suitable for cell therapy, organ chips, and tissue engineering applications. However, achieving a uniform cell distribution within the 3D matrix while mitigating the effects of reactive oxygen species (ROS) accumulation generated during the 3D cell culture remains a critical challenge. Hydrogel actuators, with their excellent bioactivity and controllable self-rolling behavior, provide an optimal microenvironment for the 3D cell culture. To support normal cellular function, hydrogel actuators must be triggered by external stimuli that are biocompatible with the cell culture process. Glucose, a key intermediate in energy metabolism and biological processes, is ubiquitous in cell culture media and physiological systems. In this work, a glucose-responsive hydrogel actuator (AP@Que/gelatin) with controllable self-rolling behaviors and ROS scavenging capability was constructed for 3D cell culture, which consists of an active layer composed of phenylboronic acid (PBA)-quercetin (Que) complexes and a passive layer of a biocompatible gelatin hydrogel. The hydrogel actuator exhibited excellent glucose response performance, characterized by notable reswelling behavior, favorable ductility, and cytocompatibility. Its self-rolling behavior in high-glucose culture media was synchronized with cell adhesion timelines, enabling its application as a 2D-to-3D…

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