Photochemistry as a tool for dynamic modulation of hydrogel mechanics

Photochemistry has emerged as a powerful tool for manipulating the dynamic and heterogeneous properties of hydrogel microenvironments in tissue engineering and mechanobiology. Enhanced spatiotemporal control over hydrogel mechanical properties can be achieved by incorporating an array of photosensitive functional groups within polymer networks and controlling photokinetics through light illumination. This review explores how light-stimulated photocleavage, addition, exchange, and isomerization reactions are utilized to generate hydrogels that soften and stiffen in situ, enabling precise control over cell functionality in tissue-engineered constructs. Advancements in polymer design and biofabrication platforms that have enhanced control over these reactions and that permit local modulation of mechanical properties within larger microenvironments are discussed. The applications of these dynamic hydrogels in understanding cellular mechanosensation, investigating fibrotic disease, and directing stem cell differentiation and tissue formation are examined. While significant progress has been made toward on-demand platforms that switch between multiple mechanical conditions, this review highlights the need for materials that undergo progressive dynamic stiffening. The review also explores emerging applications of photochemistry in intracellular environments and its potential integration with advanced force spectroscopy techniques for live-cell mechanobiology studies. Overall, using light as a stimulus for reactions within hydrogels has enhanced tunability, reaction kinetics, and spatiotemporal control compared to other stimuli-driven systems, opening new avenues for biomimetic material design and mechanobiological investigations.