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Liposomes, with their exceptional biocompatibility, structural versatility, and ability to encapsulate diverse therapeutics, have emerged as a cornerstone of nanomedicine. This review provides a function\u2010centric analysis of how liposomes are engineered as intelligent, multi\u2010functional platforms to tackle the specific challenges of the bone microenvironment. We move beyond a simple catalog of applications to critically examine the design strategies that enable liposomes to: (1) penetrate biofilm barriers and eradicate intracellular pathogens in infectious bone diseases; (2) actively target and reprogram inflammatory cells to resolve chronic inflammation in arthritis; (3) provide spatiotemporal control over growth factor and gene delivery for enhanced bone and cartilage regeneration; and (4) enable combinatorial chemo\u2010gene therapies and novel cytotoxic mechanisms for osteosarcoma. By comparing and contrasting these strategies, this review identifies key technological advancements\u2014such as stimuli\u2010responsive release, biomimetic camouflage, and stem\u2010cell fate engineering\u2014that are driving the field forward. We conclude by discussing the persistent challenges for clinical translation and outlining future directions for the next generation of \u201csmart\u201d liposomes that promise to transform the paradigm of orthopedic treatment from symptomatic management to pathology\u2010modifying and regenerative intervention.<\/jats:p>","DOI":"10.1002\/jbm.b.70089","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:31:21Z","timestamp":1777872681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liposomes: An Intelligent Drug Delivery System for Translational Applications in Bone Biomedicine"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1181-7397","authenticated-orcid":false,"given":"Weike","family":"Feng","sequence":"first","affiliation":[{"name":"Orthopedic Centre\u2010Spine Surgery The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army  Lanzhou China"},{"name":"First Clinical Medical College Gansu University of Chinese Medicine  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Xue","sequence":"additional","affiliation":[{"name":"Orthopedic Centre\u2010Spine Surgery The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Chang","sequence":"additional","affiliation":[{"name":"Orthopedic Centre\u2010Spine Surgery The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army  Lanzhou China"},{"name":"First Clinical Medical College Gansu University of Chinese Medicine  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Orthopedic Centre\u2010Spine Surgery The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army  Lanzhou China"},{"name":"First Clinical Medical College Gansu University of Chinese Medicine  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruitang","family":"Liu","sequence":"additional","affiliation":[{"name":"Orthopedic Centre\u2010Spine Surgery The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army  Lanzhou China"},{"name":"First Clinical Medical College Gansu University of Chinese Medicine  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Orthopedic Centre\u2010Spine Surgery The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army  Lanzhou China"},{"name":"First Clinical Medical College Gansu University of Chinese Medicine  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longwen","family":"Zhan","sequence":"additional","affiliation":[{"name":"Orthopedic Centre\u2010Spine Surgery The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army  Lanzhou China"},{"name":"First Clinical Medical College Gansu University of Chinese Medicine  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuming","family":"Gao","sequence":"additional","affiliation":[{"name":"Orthopedic Centre\u2010Spine Surgery The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Fan","sequence":"additional","affiliation":[{"name":"Orthopedic Centre\u2010Spine Surgery The 940 Hospital of Joint Logistics Support Force of Chinese People's Liberation Army  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-0286(96)80031-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1632"},{"key":"e_1_2_8_4_1","unstructured":"D. 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