Injectable and transient hydrogel with programmable lifetime by endogenous coordination crosslinking and enzymatic de-crosslinking

We developed an injectable and transient hydrogel with a programmable lifetime by introducing closed functional loops, specifically gelation and sol transition pathways, within the system. Gelation occurs through the formation of coordination crosslinking between a phosphate ester and its affinity ligand, while enzymatic degradation of the phosphate ester triggers the sol transition pathway. The transition from the gel to the sol state was driven by the dissipation of a transient thermodynamic state under out-of-equilibrium conditions. The transient gel persisted because of the kinetic imbalance between fast gelation and the slow sol transition pathway. By tuning the kinetic balance of these pathways, the lifetime of the transient hydrogel was programmed over a wide range—from within an hour to three months. Additionally, the ability of the hydrogel to control the payload release induced by sol transition was validated. The unique properties of the present system are expected to have applications in drug delivery systems tailored to patient needs and objectives, as well as in scaffold materials for tissue engineering.