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Unlike previous industrial enzyme\u2010focused studies, a rigid\u2010flexible layered immobilization strategy integrating networked metal\u2013organic frameworks (MOFs) into flexible hydrogels is proposed. This innovative strategy stabilizes enzyme conformation, strengthens enzyme\u2010matrix interactions, and prevents enzyme leakage via a dual\u2010pore system. This synergistic system, composed of MOF micropores (50\u2013150\u00a0nm, confinement) and hydrogel macropores (800\u2013900\u00a0nm, mass transfer), resolves the stability\u2010accessibility trade\u2010off. Molecular docking shows MOFs reduce substrate\u2010enzyme distance by 34.2% and enhance rigidity. In industrial biocatalysis, immobilized horseradish peroxidase maintains robust conversion efficiency for the reaction of 1\u00a0\n                    <jats:sc>M<\/jats:sc>\n                    <jats:italic>o<\/jats:italic>\n                    \u2010phenylenediamine over 40 cycles, effectively promoting the production efficiency of related chemical products. In the biomedical field, immobilizing thrombin reduces murine wound bleeding by 55%, providing a new solution to wound hemostasis. This scalable platform integrates nanoscale precision with macroscale responsiveness, holding great promise for advancing sustainable biocatalysis and biomedicine.\n                  <\/jats:p>","DOI":"10.1002\/smll.202512609","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:53:26Z","timestamp":1768913606000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Rigid\u2010Flexible Layered Immobilization Enables Precise Confinement and Dynamic Activation of Small Enzymes"],"prefix":"10.1002","volume":"22","author":[{"given":"Jia\u2010Qi","family":"Zhu","sequence":"first","affiliation":[{"name":"College of Biotechnology and Bioengineering Zhejiang University of Technology  Hangzhou Zhejiang China"},{"name":"Zhejiang Key Laboratory of Green Manufacturing Technology for Chemical Drugs  Deqing Zhejiang China"},{"name":"Key Laboratory for Green Pharmaceutical Technology and Equipment 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