A 4‐Arm PEG‐Thiodepsipeptide Precursor Enables Gelatinase‐Promoted Hydrogel Formation

In situ hydrogelation of injectable precursors upon biological stimulus is relevant to generate hydrogels under mild conditions and, potentially, at a side interest. Here, it shown that hydrolytic enzymes can be used initiate the formation covalent hydrogel networks, realizing cleavage-leading-to-gelation strategy. For this purpose, two-component system used, consisting 4-arm polyethylene glycol-thiodepsipeptide conjugate, PEG4TDPo containing matrix metalloproteinases MMP-2- and MMP-9-cleavable Ac-Pro-Leu-Gly#SLeu-Leu-Gly- thiodepsipeptide sequence releasing thiol hydrolysis, maleimide functionalized 4-armed PEG (PEG4MAL). synthesized in PEG-functionalization protocol involving convergent divergent synthetic steps without need for rigorous purification procedures. fluorometric assay, construct fact cleaved by both investigated MMPs. presence 10 wt.% PEG4MAL formed addition MMP-2 or -9 with average gelation times 28 40 min, respectively, as rheology. The much faster compared enzyme-free showed specific input enzymatic reactions. MMP-assisted activation crosslinking strategy potentially become useful targeting tissues showing an increased expression MMPs, such cancers, detect