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Despite advances in designer materials, few techniques effectively provide auto\u2010regulated feedback mechanisms that govern how cells sense and respond to discrete microenvironmental changes. Here, we demonstrate that the artificial, juxtacrine\u2010like receptor synthetic Notch (synNotch) can be activated by endogenous multimeric cytokines in solution, without immobilizing materials, revealing a previously unreported activation modality and yielding up to 24\u2010fold dynamic range. 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Thus, nMATRIX couples native soluble cues to customized cellular responses with tunable sensitivity, offering a flexible materials\u2010based approach for self\u2010regulating regenerative therapies.<\/jats:p>","DOI":"10.1002\/adhm.71481","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:52:32Z","timestamp":1785300752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Encoded Cell\u2010Material Interactions to Reroute Cytokine Signaling for Regenerative Medicine"],"prefix":"10.1002","volume":"15","author":[{"given":"Zachary M.","family":"Eidman","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhanvi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville 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