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Hybrid Dynamic–Covalent PEG Hydrogels With Enhanced Stability for Photothermally Triggered Pulsatile Drug Delivery

Aug 2026 · Macromolecular Bioscience · Vol 26 · 0 citations · 37 references
Medicine

Abstract

Hydrogels are three‐dimensional elastic networks that have applications in wide array of biomedical fields. Hydrogels can be crosslinked via dynamic covalent bonds (DCB) in order to done them with the ability to be injected, to self‐heal, and to respond to stimuli. In our previous work, reversible thiol‐conjugate crosslinks were used in the preparation of dynamic poly(ethylene glycol) (PEG) hydrogels. Because the equilibrium state of these reversible thiol‐conjugate bonds can be shifted by temperature, both thermal and photothermal stimuli were used to induce the gel‐to‐sol transition of these materials to develop an on‐demand pulsatile cargo release. However, the dynamic nature of the crosslinks resulted in rapid gel dissolution that prevented their use for long‐term drug delivery. In this work, the hydrogels were complemented with stable thiol‐maleimide crosslinks to decrease their dissolution rate and prolong their functional lifetime. Data shows that even a small addition of thiol‐maleimide crosslinks significantly stabilizes the hydrogels, providing improved control of cargo release initiated by photothermal stimuli but does not cause a notable difference in cargo release at physiological temperature when compared to the hydrogels lacking the stable thiol‐maleimide crosslinks.

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