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Though their precursors can be readily synthesized with near\u2010perfect monodispersity and sequence specificity through scalable fermentation processes, recombinant protein materials have yet to achieve the same level of multi\u2010stimuli\u2010responsiveness as their synthetic counterparts. Integrating cutting\u2010edge tools from chemical biology, we autonomously compile topologically specified protein crosslinkers that can be degraded following user\u2010programmable Boolean logic. Covalent step polymerization of these linkers into protein hydrogels yields smart materials whose cargo (e.g., bioactive proteins, cellular therapeutics) can be liberated following bulk degradation in response to user\u2010specified input combinations. Demonstrating the versatility of this approach, we release fluorescent protein mGreenLantern following all 17 possible YES\/OR\/AND logic outputs in response to a 3\u2010input protease operator set, deliver epidermal growth factor following advanced biocomputation while maintaining native bioactivity, and showcase multiplexed delivery of living cells, all from fully recombinant protein\u2010based hydrogels. Incorporating advanced intelligence into protein biomaterial responsiveness, we anticipate these methods will dramatically expand potential applications in tissue engineering and precision medicine.<\/jats:p>","DOI":"10.1002\/adma.74038","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:37:12Z","timestamp":1784623032000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Boolean Logic\u2010Based Control Over Recombinant Protein Biomaterial Degradability and Therapeutic Delivery"],"prefix":"10.1002","volume":"38","author":[{"given":"Murial L.","family":"Ross","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Gharios","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering University of Washington  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