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However, challenges such as the lack of feedback-regulated functionality and microenvironmental modulation persist. Here, we developed an osteoporotic microenvironment-responsive implant coating that integrates feedback-regulated release of the anti-osteoporotic drug strontium ranelate (SR) with oxidative stress neutralization. A reactive oxygen species (ROS)-responsive and -regulating nanocoating was fabricated on SR-loaded titania nanotube arrays (TNTAs-SR) via host\u2013guest complexation between \u03b2-cyclodextrin-conjugated ceria nanoparticles (CeNPs-\u03b2-CD) and ferrocene-modified polydopamine (PDA-Fc). The CeNPs-\u03b2-CD served dual roles as antioxidant nanozymes and ROS-responsive nanolids through reversible \u03b2-CD\/Fc interactions. The resulting PDA-CeNP nanocoating exhibited exceptional antioxidative capacity against multiple ROS through the combined action of PDA-Fc and CeNPs-\u03b2-CD. Owing to its reversible redox sensitivity, TNTAs-SR\/PDA-CeNPs enabled rapid SR release under high H2O2 levels and delayed release upon H2O2 depletion, achieving \u201csense-feedback\u201d drug delivery. In vitro, TNTAs-SR\/PDA-CeNPs had greater protective effects on osteoblastic functions against H2O2-induced oxidative stress and attenuated osteoclast differentiation. In an osteoporotic rat model, TNTAs-SR\/PDA-CeNPs eliminated ROS and lipid peroxidation in bone tissue, inhibited fibrosis, and maximally enhanced osseointegration. Overall, this smart implant coating, capable of rescuing the pathological ROS microenvironment while delivering therapeutic agents on demand, holds substantial promise for osteoporotic bone healing.<\/jats:p>","DOI":"10.1021\/acsami.6c13502","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:01:53Z","timestamp":1789178513000},"page":"50570-50585","source":"Crossref","is-referenced-by-count":1,"title":["Smart Implant Coating with Pathological-Microenvironment-Driven Drug and Nanozyme Delivery for Osteoporotic Bone Healing"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-4836","authenticated-orcid":true,"given":"Kai","family":"Li","sequence":"first","affiliation":[{"name":"Shanghai Institute of Ceramics, Chinese Academy of Sciences , , 585 Heshuo Road , ,","place":["Shanghai, China, 201899"]},{"name":"University of Chinese Academy of Sciences , , 1 Yanqi Lake East Road , ,","place":["Beijing, China, 101408"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8800-2494","authenticated-orcid":true,"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Changzheng Hospital, Naval Medical University , , 415 Fengyang Road , ,","place":["Shanghai, China, 200003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3683-8556","authenticated-orcid":true,"given":"Xiaodong","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Changzheng Hospital, Naval Medical University , , 415 Fengyang Road , ,","place":["Shanghai, China, 200003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9120-5657","authenticated-orcid":true,"given":"Tao","family":"Hu","sequence":"additional","affiliation":[{"name":"Shanghai East Hospital, Tongji University School of Medicine , , 150 Jimo Road , ,","place":["Shanghai, China, 200120"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Yangpu Hospital, Tongji University School of Medicine , , 2200 Pingliang Road , ,","place":["Shanghai, China, 200090"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1258-3038","authenticated-orcid":true,"given":"Yulin","family":"Gao","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Ceramics, Chinese Academy of Sciences , , 585 Heshuo Road , ,","place":["Shanghai, China, 201899"]},{"name":"University of Chinese Academy of Sciences , , 1 Yanqi Lake East Road , ,","place":["Beijing, China, 101408"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2847-2263","authenticated-orcid":true,"given":"Yi","family":"Ding","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Ceramics, Chinese Academy of Sciences , , 585 Heshuo Road , ,","place":["Shanghai, China, 201899"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1245-200X","authenticated-orcid":true,"given":"Xuebin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Ceramics, Chinese Academy of Sciences , , 585 Heshuo Road , ,","place":["Shanghai, China, 201899"]},{"name":"University of Chinese Academy of Sciences , , 1 Yanqi Lake East Road , ,","place":["Beijing, China, 101408"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"2026100820084219400_cit1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41413-019-0066-7","article-title":"Bench-to-bedside strategies for osteoporotic fracture: From osteoimmunology to mechanosensation","volume":"7","author":"Xie","year":"2019","journal-title":"Bone Res."},{"issue":"10","key":"2026100820084219400_cit2","doi-asserted-by":"publisher","first-page":"3859","DOI":"10.7150\/thno.96516","article-title":"Osteoporotic osseointegration: therapeutic hallmarks and engineering strategies","volume":"14","author":"Chen","year":"2024","journal-title":"Theranostics"},{"key":"2026100820084219400_cit3","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.addr.2020.10.011","article-title":"Synergistic use of biomaterials and licensed therapeutics to manipulate bone remodelling and promote non-union fracture repair","volume":"160","author":"Simpson","year":"2020","journal-title":"Adv. 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