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There is an urgent need to design and construct versatile engineered implants integrated with cascade amplification therapeutic modality to significantly improve the treatment of diabetic IAIs. To address this issue, a multi\u2010functional MXene\/Ag<jats:sub>3<\/jats:sub>PO<jats:sub>4<\/jats:sub>@glucose oxidase bio\u2010heterojunction enzyme (M\/A@GOx bio\u2010HJzyme) coating is developed, which is decorated with an inert sulfonated polyetheretherketone implant (SP\u2010M\/A@G) via hydrothermal treatment and layered deposition. The decorated bio\u2010HJzyme coating promoted cellular adhesion and proliferation of osteoblast cells on the implant. Simultaneously, upon 808 nm near\u2010infrared (NIR) light irradiation, the decorated coating not only induces localized hyperthermia and reactive oxygen species (ROS) generation but also initiates Fenton\u2010like and laccase\u2010mimicking reactions and depletes glutathione (GSH) within the diabetes infection microenvironment. The cascade amplification therapeutic effects of phototherapy and biocatalytic therapy confer the engineered implants with robust cyclic antibacterial properties. Furthermore, in vivo, assessment demonstrated that the multi\u2010functional bio\u2010HJzyme can effectively eradicate infectious pathogens located on the implant and peri\u2010implant tissues and promote the regeneration of diabetic infectious skin. Collectively, this study provides a revolutionary approach for constructing multi\u2010functional implants with cascade amplification therapeutic capabilities for intractable diabetic IAIs.<\/jats:p>","DOI":"10.1002\/smll.202409437","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T15:22:54Z","timestamp":1735658574000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Multi\u2010Functional Bio\u2010HJzyme Engineered Polyetheretherketone Implant with Cascade\u2010Amplification Therapeutic Capabilities Toward Intractable Implant\u2010Associated Infections"],"prefix":"10.1002","volume":"21","author":[{"given":"Jing","family":"Gong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases School of Chemical Engineering National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases Sichuan University  Chengdu 610041 China"},{"name":"Department of Cariology and Endodontics West China Hospital of Stomatology Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangquan","family":"Lai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases School of Chemical Engineering National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases School of Chemical Engineering National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunneng","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases School of Chemical Engineering National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases Sichuan University  Chengdu 610041 China"},{"name":"Department of Cariology and Endodontics West China Hospital of Stomatology Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1765-5244","authenticated-orcid":false,"given":"Yi","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases School of Chemical Engineering National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases Sichuan University  Chengdu 610041 China"},{"name":"Department of Mechanical Engineering The University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,31]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00104-23"},{"key":"e_1_2_8_1_2","first-page":"64","volume":"20","author":"Hofer U.","year":"2022","journal-title":"Nat. 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