Guanosine‐Quadruplex Hydrogels as Dynamic, Mechanically Tunable and Ion Conductive 3D Scaffolds for Cell Culture Applications

ABSTRACT Hydrogels are widely used materials for biomedical applications. In particular, supramolecular hydrogels based on guanosine‐quadruplexes (GQ) have been utilized for drug delivery, biocatalysis, and biosensing. However, when applied as scaffolds for cell culture, existing GQ hydrogels suffer from important limitations: (i) scarcity of mild fabrication strategies, (ii) quick disintegration within few hours under physiological conditions, (iii) narrow tunability of their properties in relation to native tissues. These shortcomings hamper the broad use of GQ hydrogels in biomedicine. Herein, stable and versatile GQ hydrogels are developed as dynamic biomatrices for cell culture applications. The GQ matrices are easily fabricated under mild aqueous conditions, present improved stability and tunable mechanical properties within physiological ranges; fibrillar, porous microstructure, ion conductivity and cytocompatibility. Detailed characterization of GQ self‐assembly process driving hydrogelation is presented through various techniques. These matrices support the culture of diverse cell types in 2D and 3D, and showcase injectability and printability, making these scaffolds suitable for manufacturing soft medical devices. The results of this study expand the applicability potential of GQ hydrogels for advancing cell culture and in vitro tissue model technologies.