In Situ Stiffness Tunable DNA Hydrogels Based on Ring‐Opening Polymerization

Abstract DNA hydrogels are promising artificial extracellular matrices (ECMs) due to their programmability and biocompatibility. However, most current stiffness modulation strategies are static, with limited dynamic regulation due to the restricted responsiveness of the building blocks. Here, a ring‐opening polymerization strategy is presented based on supramolecular dimer rings containing functional domains to achieve in situ regulation of DNA hydrogel stiffness. The rings consist of complementary regions, flexible spacers, and sticky ends. Upon the addition of linkers, the rings polymerize into linear polymers that form a hydrogel through physical entanglement. Hybridization with trigger strands induces ring‐opening, leading to network remodeling and enhanced stiffness, while strand displacement enables reversible stiffness reduction. This approach allows dynamic and programmable mechanical regulation under physiological conditions, providing a biomimetic platform to mimic dynamic ECM stiffening.