{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:53:25Z","timestamp":1790024005015,"version":"4.0.1"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002865","name":"Chongqing Municipal Science and Technology Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Orthopedic implant failure due to inadequate osseointegration and infection remains a critical challenge. To address this, we engineered a polydopamine (PDA)-mediated dual-functional platform for lithium (Li<jats:sup>+<\/jats:sup>) and copper (Cu<jats:sup>2+<\/jats:sup>) co-incorporation on titanium alloy (Ti6Al4V) implants, aiming to synergize osteogenic and antibacterial properties through a scalable surface modification strategy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PDA coatings were polymerized onto polished Ti64 substrates, followed by sequential immersion in LiCl (800 \u03bcM) and CuCl<jats:sub>2<\/jats:sub> (10 \u03bcM) solutions to construct Li<jats:sup>+<\/jats:sup>\/Cu<jats:sup>2+<\/jats:sup> co-doped surfaces (PDA@Li 800-Cu 10). In vitro assays assessed MC3T3-E1 pre-osteoblast proliferation (CCK-8), osteogenic differentiation (ALP activity, RT-PCR for <jats:italic>ALP\/Axin2<\/jats:italic>), and antibacterial activity against S. aureus and E. coli (live\/dead staining, CFU assays). In vivo efficacy was evaluated in a rat femoral defect model via micro-CT and histology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Li<jats:sup>+<\/jats:sup>-functionalized surfaces (PDA@Li 800) enhanced osteoblast proliferation and osteogenesis via Wnt\/\u03b2-catenin activation. Cu<jats:sup>2+<\/jats:sup>-loaded coatings (PDA@Cu 10) eradicated &amp;gt;99% bacteria but moderately suppressed osteogenic markers. The dual-doped PDA@Li 800-Cu 10 surface resolved this bioactivity conflict, maintaining antibacterial efficacy comparable to PDA@Cu 10 while elevating the osteogenic capacity of Cu<jats:sup>2+<\/jats:sup>-only modified surfaces. In vivo, dual-modified implants eliminated bacterial colonization within 72 h and significantly increased peri-implant bone volume (BV\/TV) in comparison to Ti64 controls, outperforming PDA-only counterparts. By harmonizing Li-driven osteoinduction and Cu-mediated bactericidal action through a scalable PDA platform, this work advances a transformative strategy for next-generation orthopedic and dental implants, simultaneously addressing infection risks and bone regeneration demands.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbioe.2025.1593545","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T05:39:17Z","timestamp":1747028357000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Dual-functional titanium implants via polydopamine-mediated lithium and copper co-incorporation: synergistic enhancement of osseointegration and antibacterial efficacy"],"prefix":"10.3389","volume":"13","author":[{"given":"Jun","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1242\/bio.030874","article-title":"The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of beta-catenin, a GSK3 substrate, in human glioblastoma cells","volume":"7","author":"Abdul","year":"2018","journal-title":"Biol. 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