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Post-traumatic osteoarthritis (PTOA) is an important subtype of OA which develops after joint injury. The anti-PTOA effects of iontophoretic liposome-encapsulated strontium ranelate (L-SR) combined with low-intensity pulsed ultrasound (LIPUS) were examined by a culture of human OA chondrocytes (HOACs) in alginate beads and verified on an anterior cruciate ligament transection PTOA rat model. The aim of this study is to evaluate and establish an anti-PTOA therapy combined with L-SR, transdermal iontophoresis, and LIPUS. Treatment with 10\u22124 M L-SR with LIPUS-enhanced type II collagen and glycosaminoglycans (GAGs) as L-SR with LIPUS reduced the MMP-13, IL-1\u03b2, and TNF-\u03b1 in HOACs. Iontophoretic L-SR at 15 mg with LIPUS increased the weight bearing, exercise endurance, GAG density, and type II collagen intensity, while L-SR with or without LIPUS further decreased MMP13 and proinflammatory cytokines in vivo. The RBC, WBC, and serum biochemistry values were not significantly affected by the treatments. Liposome encapsulation and iontophoresis reinforce the anti-PTOA effects of SR and the addictive LIPUS further improves weight-bearing and endurance performance in the rats with PTOA. Thus, iontophoretic L-SR with LIPUS could be a potential therapy for PTOA.<\/jats:p>","DOI":"10.3390\/ijms26188815","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T12:04:55Z","timestamp":1757505895000},"page":"8815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Amelioration of Post-traumatic Osteoarthritis by Iontophoretic Liposomal Strontium Ranelate Collaborated with Low-Intensity Pulsed Ultrasound in Rats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8941-4792","authenticated-orcid":false,"given":"Chung-Hwan","family":"Chen","sequence":"first","affiliation":[{"name":"Orthopedic Research Center, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan"},{"name":"Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan"},{"name":"Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan"},{"name":"Ph.D. Program in Biomedical Engineering, College of Medicine, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan"},{"name":"School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan"},{"name":"Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung City 804201, Taiwan"},{"name":"Graduate Institute of Materials Engineering, College of Engineering, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syu-Lun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, National Chiayi University, Chiayi City 60054, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shyh Ming","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, I-Shou University, Kaohsiung City 82445, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2237-1526","authenticated-orcid":false,"given":"Jyh-Mirn","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, National Chiayi University, Chiayi City 60054, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Ling","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Chih","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Wen","family":"Kuo","sequence":"additional","affiliation":[{"name":"Orthopedic Research Center, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han Hsiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, National Chiayi University, Chiayi City 60054, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16044","DOI":"10.1038\/boneres.2016.44","article-title":"Osteoarthritis: Toward a comprehensive understanding of pathological mechanism","volume":"5","author":"Chen","year":"2017","journal-title":"Bone Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.14336\/AD.2019.1116","article-title":"Infrapatellar Fat Pad and Knee Osteoarthritis","volume":"11","author":"Zeng","year":"2020","journal-title":"Aging Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"491","DOI":"10.4085\/1062-6050-51.5.08","article-title":"Epidemiology of Posttraumatic Osteoarthritis","volume":"52","author":"Thomas","year":"2017","journal-title":"J. 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