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These vulnerabilities severely limit catalytic longevity and practical efficacy, particularly for acetaldehyde detoxification in humans. Achieving durable enzymatic function in such hostile conditions requires a protective strategy that can physically armor enzymes while preserving molecular accessibility to substrates\u2014an unresolved challenge in current biomaterial designs. Here, we introduce a bioarmored enzyme cascade by embedding an alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) dual-enzyme system within a villus-structured hydrogel (ADH\/ALDH@VH). This collagen-based microscale grid and artificial villus architecture construct a hierarchical protective shell that mechanically stabilizes the enzymes, offers microenvironmental protection, prevents denaturation, and simultaneously preserves efficient mass transport. This bioarmoring strategy reconciles the long-standing conflict between enzyme protection and catalytic efficiency, yielding exceptional mechanical robustness and enhanced enzymatic kinetics (Kcat\/Km increased by \u223c1.1-fold relative to free enzymes). As a result, ADH\/ALDH@VH retains high activity under acidic gastric conditions where free enzymes rapidly inactivate, enabling a 3020% enhancement in acetaldehyde metabolism under harsh environments. This bioarmored cascade establishes a generalizable platform for safeguarding fragile biocatalysts in hostile biological niches, opening opportunities for enzyme therapeutics in environments previously considered inaccessible.<\/jats:p>","DOI":"10.1021\/acsami.6c11681","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:19:44Z","timestamp":1785849584000},"page":"43194-43201","source":"Crossref","is-referenced-by-count":0,"title":["A Bioarmored Enzyme Cascade for Sustained Catalysis in Harsh Microenvironments"],"prefix":"10.1021","volume":"18","author":[{"given":"Yahui","family":"Wen","sequence":"first","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Dalian, China, 116023"]},{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keqiang","family":"Lai","sequence":"additional","affiliation":[{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Dalian, China, 116023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenming","family":"Ma","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Dalian, China, 116023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghai","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Dalian, China, 116023"]},{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xia","sequence":"additional","affiliation":[{"name":"Beijing University of Technology , , ,","place":["Beijing, China, 100020"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing University of Technology , , ,","place":["Beijing, China, 100020"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4001-6385","authenticated-orcid":true,"given":"Rong","family":"Cao","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Dalian, China, 116023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoran","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Dalian, China, 116023"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6397-6516","authenticated-orcid":true,"given":"Lidong","family":"Wu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Dalian, China, 116023"]},{"name":"Shanghai Ocean University , , ,","place":["Shanghai, China, 201306"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-7811","authenticated-orcid":true,"given":"Jiping","family":"Chen","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Dalian, China, 116023"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"issue":"1-6","key":"2026081917060921500_cit1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.pisc.2014.02.005","article-title":"Enzyme assays","volume":"1","author":"Bisswanger","year":"2014","journal-title":"Perspect. 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