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To address this problem, this study developed 3D-printed \u03b2-tricalcium phosphate (TCP) scaffolds loaded with quercetin-loaded nanostructured lipid carriers (Que-NLCs) to combine an osteoconductive ceramic structure with local delivery of a natural osteogenic and anti-resorptive compound. Que-NLCs provided controlled release for up to 21 days and reduced the initial burst release compared with free Que at both pH 5.0 and 7.4. At pH 5.0, release was \u223c40% for Que and \u223c33% for Que-NLCs, while at pH 7.4, release was \u223c32% for Que and \u223c26% for Que-NLCs. In vitro studies showed that Que-NLC-loaded scaffolds increased osteoblast viability by \u223c28.6%, increased alkaline phosphatase activity by 33% by day 11, and reduced osteoclastic activity by 56% by day 21. RT-qPCR further showed up to 4-fold increases in osteogenic markers and up to 60% reduction in osteoclastogenesis-related genes. In a 6-week rat distal femur model, Que-NLC scaffolds increased new bone formation by \u223c1.9-fold compared with TCP. These results show that Que-NLC-TCP scaffolds provide a localized, controlled drug-delivery platform to improve bone regeneration in non-load-bearing defects.<\/jats:p>","DOI":"10.1021\/acsami.6c06921","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:01:11Z","timestamp":1791655271000},"page":"55793-55805","source":"Crossref","is-referenced-by-count":0,"title":["Nanostructured Quercetin-Lipid Carrier on 3D Printed Scaffolds for Improved Bone Regeneration"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8296-2630","authenticated-orcid":true,"given":"Priya","family":"Kushram","sequence":"first","affiliation":[{"name":"Washington State University , , , ,","place":["Pullman, Washington, United States, 99164"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8601-016X","authenticated-orcid":true,"given":"Susmita","family":"Bose","sequence":"additional","affiliation":[{"name":"Washington State University , , , ,","place":["Pullman, Washington, United States, 99164"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"issue":"28","key":"2026102609071182000_cit1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2427124122","article-title":"Osteoinductive Low-Dose 3D Porous Calcium Phosphate Graphene Oxide\u2013Integrated Matrices Enhance Osteogenesis and Mechanical Properties","volume":"122","author":"Hosseini","year":"2025","journal-title":"Proc. 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