@misc{folikumah_a_4arm_2023, 
author={Folikumah, M.Y., Behl, M., Lendlein, A., Neffe, A.T.},
title={A 4-Arm PEG-Thiodepsipeptide Precursor Enables Gelatinase-promoted Hydrogel Formation},
year={2023},
howpublished = {journal article},
doi = {https://doi.org/10.1002/mame.202300146},
abstract = {In situ hydrogelation of injectable precursors upon biological stimulus is relevant to generate hydrogels under mild conditions and, potentially, at a biological side of interest. Here, it is shown that hydrolytic enzymes can be used to initiate the formation of covalent hydrogel networks, realizing a cleavage-leading-to-gelation strategy. For this purpose, a two-component system is used, consisting of a 4-arm polyethylene glycol-thiodepsipeptide conjugate, PEG4TDPo containing the matrix metalloproteinases MMP-2- and MMP-9-cleavable Ac-Pro-Leu-Gly#SLeu-Leu-Gly- thiodepsipeptide sequence releasing a thiol upon hydrolysis, and a maleimide functionalized 4-armed PEG (PEG4MAL). PEG4TDPo is synthesized in a PEG-functionalization protocol involving convergent and divergent synthetic steps without the need for rigorous purification procedures. In a fluorometric assay, it is shown that the construct is in fact cleaved by both investigated MMPs. PEG4TDPo in the presence of 10 wt.% PEG4MAL formed hydrogels upon addition of MMP-2 or -9 with average gelation times of 28 and 40 min, respectively, as is investigated by rheology. The much faster gelation times compared to the enzyme-free system showed the specific input of the enzymatic reactions. The MMP-assisted activation and crosslinking strategy can potentially become useful by targeting tissues showing an increased expression of MMPs, such as cancers, or to detect MMPs.},
note = {Online available at: \url{https://doi.org/10.1002/mame.202300146} (DOI). Folikumah, M.; Behl, M.; Lendlein, A.; Neffe, A.: A 4-Arm PEG-Thiodepsipeptide Precursor Enables Gelatinase-promoted Hydrogel Formation. Macromolecular Materials and Engineering. 2023. vol. 308, no. 11, 2300146. DOI: 10.1002/mame.202300146}}