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. 2024 Feb 27;23(9):1292–1299. doi: 10.1038/s41563-024-01811-5

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, LIFT hydrogels form within the stomach after oral administration of (1) a 200-ml crosslinker solution comprising CaCl₂ and a dithiol-containing molecule, followed by (2) a 20–40-ml polymer solution comprising alginate and four-arm PEG–maleimide. These two solutions (3) mix within the stomach to form a tough double-network hydrogel (4) within the stomach. b, Schematic of the polymers and reagents used to facilitate crosslinking. Materials were selected due to their established safety profiles. Both PEG–dithiol and dimercaptosuccinic acid (DMSA) were investigated as a dithiol crosslinker. c, Left: LIFT hydrogels may act as controlled release depots through encapsulation of water-insoluble drug that gradually dissolves and diffuses from the hydrogel. Middle and right: LIFT hydrogels enable co-encapsulation and co-localization of therapeutic microbes or enzymes and excipient (for example, CaCO₃) that modulate local pH and protect against proteases.