Intracellular gelation of biomaterials: strategies, characterization, and biomedical applications

Recently, researchers have developed innovative cell engineering strategies that draw inspiration from naturally occurring intracellular gel-like substances and advanced cell engineering strategies designed to maintain the structural integrity and functionality of cells. These strategies involve the introduction of exogenous materials into living cells, where hydrogel formation occurs via chemistry reactions or physical interactions of the materials. The gelation process can be initiated either independently of the intracellular environment or in response to intracellular conditions. This review highlights recent progress in intracellular gelation strategies, emphasizing the mechanisms of material delivery into cells and the diverse pathways that trigger gel formation within the intracellular milieu. Additionally, we have comprehensively reviewed and integrated the current techniques available for characterizing intracellular gel formation. Furthermore, we explore the applications of intracellular gelation, particularly in cellular immobilization and modulation of living cell behavior. Finally, we discuss the potential of intracellular gelation as a transformative strategy in cell engineering and next-generation biomaterials, outline current challenges, and propose perspectives for future research and technological advancement in this emerging field.