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Hydrolytically Degradable PEG-Based Inverse Electron Demand Diels–Alder Click Hydrogels

[Image: see text] Hydrogels cross-linked by inverse electron demand Diels–Alder (iEDDA) click chemistry are increasingly used in biomedical applications. With a few exceptions in naturally derived and chemically modified macromers, iEDDA click hydrogels exhibit long-term hydrolytic stability, and no...

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Detalles Bibliográficos
Autores principales: Dimmitt, Nathan H., Arkenberg, Matthew R., de Lima Perini, Mariana Moraes, Li, Jiliang, Lin, Chien-Chi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554872/
https://www.ncbi.nlm.nih.gov/pubmed/36074814
http://dx.doi.org/10.1021/acsbiomaterials.2c00714
Descripción
Sumario:[Image: see text] Hydrogels cross-linked by inverse electron demand Diels–Alder (iEDDA) click chemistry are increasingly used in biomedical applications. With a few exceptions in naturally derived and chemically modified macromers, iEDDA click hydrogels exhibit long-term hydrolytic stability, and no synthetic iEDDA click hydrogels can undergo accelerated and tunable hydrolytic degradation. We have previously reported a novel method for synthesizing norbornene (NB)-functionalized multiarm poly(ethylene glycol) (PEG), where carbic anhydride (CA) was used to replace 5-norbornene-2-carboxylic acid. The new PEGNB(CA)-based thiol-norbornene hydrogels exhibited unexpected fast yet highly tunable hydrolytic degradation. In this contribution, we leveraged the new PEGNB(CA) macromer for forming iEDDA click hydrogels with [methyl]tetrazine ([m]Tz)-modified macromers, leading to the first group of synthetic iEDDA click hydrogels with highly tunable hydrolytic degradation kinetics. We further exploited Tz and mTz dual conjugation to achieve tunable hydrolytic degradation with an in vitro degradation time ranging from 2 weeks to 3 months. Finally, we demonstrated the excellent in vitro cytocompatibility and in vivo biocompatibility of the new injectable PEGNB(CA)-based iEDDA click cross-linked hydrogels.