{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T21:30:19Z","timestamp":1772055019386,"version":"3.50.1"},"reference-count":49,"publisher":"ASME International","issue":"4","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.asme.org\/publications-submissions\/publishing-information\/legal-policies"}],"funder":[{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH-16-1-0735"],"award-info":[{"award-number":["W81XWH-16-1-0735"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asmedigitalcollection.asme.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Previous studies have shown that reconstructive surgery alone following injury to the anterior cruciate ligament (ACL) does not prevent the development of post-traumatic osteoarthritis (PTOA). Poloxamer 188 (P188) has been shown to prevent cell death following trauma in both articular cartilage and meniscal tissue. This study aims to test the efficacy of single or multiple administrations of P188 in conjunction with reconstructive surgery to help prevent or delay the onset of the disease. Thirty skeletally mature rabbits underwent closed-joint trauma that resulted in ACL rupture and meniscal damage and were randomly assigned to one of four treatment groups with varying doses of P188. ACL reconstruction was then performed using an autograft from the semitendinosus tendon. Animals were euthanized 1-month following trauma, meniscal tissue was assessed for changes in morphology, mechanical properties, and proteoglycan content. Femurs and tibias were scanned using microcomputed tomography to determine changes in bone quality, architecture, and osteophyte formation. The medial meniscus experienced more damage and a decrease in the instantaneous modulus regardless of treatment group, while P188 treatment tended to limit degenerative changes in the lateral meniscus. Both lateral and medial menisci had documented decreases in the equilibrium modulus and inconsistent changes in proteoglycan content. Minimal changes were documented in the tibias and femurs, with the only significant change being the formation of osteophytes in both bones regardless of treatment group. The data suggest that P188 was able to limit some degenerative changes in the meniscus associated with PTOA and may warrant future studies.<\/jats:p>","DOI":"10.1115\/1.4052564","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T15:11:47Z","timestamp":1636470707000},"update-policy":"https:\/\/doi.org\/10.1115\/crossmarkpolicy-asme","source":"Crossref","is-referenced-by-count":3,"title":["Evaluating the Efficacy of Combined P188 Treatment and Surgical Intervention in Preventing Post-Traumatic Osteoarthritis Following a Traumatic Knee Injury"],"prefix":"10.1115","volume":"144","author":[{"given":"Gerardo E.","family":"Narez","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Massachusetts Amherst , Amherst, MA 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Massachusetts Amherst , Amherst, MA 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Herrick","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Massachusetts Amherst , Amherst, MA 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan J.","family":"Ek","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Massachusetts Amherst , Amherst, MA 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loic","family":"Dejardin","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences, Michigan State University , East Lansing, MI 48824"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Wei","sequence":"additional","affiliation":[{"name":"Orthopaedic Biomechanics Laboratories, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger C.","family":"Haut","sequence":"additional","affiliation":[{"name":"Orthopaedic Biomechanics Laboratories, College of Osteopathic Medicine, Michigan State University , East Lansing, MI 48824 ; , East Lansing, MI 48824"},{"name":"Department of Mechanical Engineering, Michigan State University , East Lansing, MI 48824 ; , East Lansing, MI 48824"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammy L.","family":"Haut Donahue","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Massachusetts Amherst , Amherst, MA 01003 ; , 240 Thatcher Road, Amherst, MA 01003"},{"name":"S631 Life Sciences Laboratory, University of Massachusetts , Amherst, MA 01003 ; , 240 Thatcher Road, Amherst, MA 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"33","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"issue":"7","key":"2022110901082358900_bib1","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.2106\/00004623-197456070-00009","article-title":"Biomechanics of Ligament Failure","volume":"56","year":"1974","journal-title":"J. Bone Jt. Surg."},{"issue":"10","key":"2022110901082358900_bib2","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1177\/0363546507307396","article-title":"The Long-Term Consequence of Anterior Cruciate Ligament and Meniscus Injuries: Osteoarthritis","volume":"35","year":"2007","journal-title":"Am. J. Sports Med."},{"key":"2022110901082358900_bib3","first-page":"152","article-title":"Five-Year Followup of Knee Joint Cartilage Thickness Changes After Acute Rupture of the Anterior Cruciate Ligament","volume-title":"Arthritis Rheumatol.","year":"2015"},{"key":"2022110901082358900_bib4","first-page":"1","article-title":"An Update on the Pathogenesis and Epidemiology of Osteoarthritis","volume-title":"Radiol. Clin. North Am.","year":"2004"},{"issue":"3","key":"2022110901082358900_bib5","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.knee.2006.01.005","article-title":"Epidemiology of Athletic Knee Injuries: A 10-Year Study","volume":"13","year":"2006","journal-title":"Knee"},{"issue":"6","key":"2022110901082358900_bib6","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.arthro.2005.03.010","article-title":"Thirty-Five Years of Follow-Up of Anterior Cruciate Ligament\u2014Deficient Knees in High-Level Athletes","volume":"21","year":"2005","journal-title":"Arthroscopy J. Arthroscopic Relat. Surg."},{"issue":"5","key":"2022110901082358900_bib7","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.knee.2006.02.014","article-title":"The Evolution of Osteoarthritis in 103 Patients With ACL Reconstruction at 17 Years Follow-Up","volume":"13","year":"2006","journal-title":"Knee"},{"issue":"3","key":"2022110901082358900_bib8","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1177\/0363546504269590","article-title":"Prospective Trial of a Treatment Algorithm for the Management of the Anterior Cruciate Ligament \u2013 Injured Knee","volume":"33","year":"2005","journal-title":"Am. J. Sports Med."},{"issue":"3","key":"2022110901082358900_bib9","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1136\/bjsm.2004.010900","article-title":"Return to Play Guidelines After Anterior Cruciate Ligament Surgery","volume":"39","year":"2005","journal-title":"Br. J. Sports Med."},{"issue":"3","key":"2022110901082358900_bib10","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1136\/ard.2003.008136","article-title":"High Prevalence of Osteoarthritis 14 Years After an Anterior Cruciate Ligament Tear in Male Soccer Players: A Study of Radiographic and Patient Relevant Outcomes","volume":"63","year":"2004","journal-title":"Ann. Rheum. Diseases"},{"key":"2022110901082358900_bib11","doi-asserted-by":"crossref","first-page":"104406","DOI":"10.1016\/j.jmbbm.2021.104406","article-title":"A Single Dose of P188 Prevents Cell Death in Meniscal Explants Following Impact Injury","volume":"117","year":"2021","journal-title":"J. Mech. Behav. Biomed. Mater."},{"issue":"6","key":"2022110901082358900_bib12","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.orthres.2005.06.001.1100230618","article-title":"The Limitation of Acute Necrosis in Retro-Patellar Cartilage After a Severe Blunt Impact to the In Vivo Rabbit Patello-Femoral Joint","volume":"23","year":"2005","journal-title":"J. Orthop. Res."},{"issue":"5","key":"2022110901082358900_bib13","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.orthres.2004.02.002","article-title":"The Use of a Non-Ionic Surfactant (P188) to Save Chondrocytes From Necrosis Following Impact Loading of Chondral Explants","volume":"22","year":"2004","journal-title":"J. Orthop. Res."},{"key":"2022110901082358900_bib14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jmbbm.2015.03.008","article-title":"Efficacy of P188 on Lapine Meniscus Preservation Following Blunt Trauma","volume":"47","year":"2015","journal-title":"J. Mech. Behav. Biomed. Mater."},{"issue":"9","key":"2022110901082358900_bib15","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1097\/BOT.0b013e3181ec4712","article-title":"Protective Effect of P188 in the Model of Acute Trauma to Human Ankle Cartilage: The Mechanism of Action","volume":"24","year":"2010","journal-title":"J. Orthop. Trauma"},{"issue":"4","key":"2022110901082358900_bib16","doi-asserted-by":"crossref","first-page":"041012","DOI":"10.1115\/1.2939368","article-title":"P188 Reduces Cell Death and IGF-I Reduces GAG Release Following Single-Impact Loading of Articular Cartilage","volume":"130","year":"2008","journal-title":"ASME J. Biomech. Eng."},{"key":"2022110901082358900_bib17","first-page":"1244","article-title":"Degradation After Acute Trauma to Human Ankle Cartilage","volume-title":"Osteoarthritis and Cartilage","year":"2010"},{"issue":"4","key":"2022110901082358900_bib18","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/jor.21022","article-title":"Acute Repair of Chondrocytes in the Rabbit Tibiofemoral Joint Following Blunt Impact Using P188 Surfactant and a Preliminary Investigation of Its Long-Term Efficacy","volume":"28","year":"2010","journal-title":"J. Orthop. Res."},{"issue":"2","key":"2022110901082358900_bib19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S1063-4584(05)80318-8","article-title":"Characterization of a Model of Osteoarthritis in the Rabbit Knee","volume":"4","year":"1996","journal-title":"Osteoarthritis Cartilage"},{"issue":"5","key":"2022110901082358900_bib20","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1063-4584(97)80039-8","article-title":"Quantitation and Localization of Cartilage Degeneration Following the Induction of Osteoarthritis in the Rabbit Knee","volume":"5","year":"1997","journal-title":"Osteoarthritis Cartilage"},{"issue":"3","key":"2022110901082358900_bib21","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1114\/1.133","article-title":"In Vivo Kinematics of the Rabbit Knee in Unstable Models of Osteoarthrosis","volume":"26","year":"1998","journal-title":"Ann. Biomed. Eng."},{"issue":"12","key":"2022110901082358900_bib22","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.joca.2004.08.010","article-title":"Ex Vivo Characterization of Articular Cartilage and Bone Lesions in a Rabbit ACL Transection Model of Osteoarthritis Using MRI and Micro-CT","volume":"12","year":"2004","journal-title":"Osteoarthritis Cartilage"},{"issue":"6","key":"2022110901082358900_bib23","doi-asserted-by":"crossref","first-page":"064501","DOI":"10.1115\/1.4001111","article-title":"Development of a Traumatic Anterior Cruciate Ligament and Meniscal Rupture Model With a Pilot In Vivo Study","volume":"132","year":"2010","journal-title":"ASME J. Biomech. Eng."},{"issue":"3","key":"2022110901082358900_bib24","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/jor.23275","article-title":"Comparison of Two Models of Post-Traumatic Osteoarthritis; Temporal Degradation of Articular Cartilage and Menisci","volume":"35","year":"2017","journal-title":"J. Orthop. Res."},{"issue":"7","key":"2022110901082358900_bib25","doi-asserted-by":"crossref","first-page":"071001","DOI":"10.1115\/1.4027468","article-title":"Evaluation of Meniscal Mechanics and Proteoglycan Content in a Modified Anterior Cruciate Ligament Transection Model","volume":"136","year":"2014","journal-title":"ASME J. Biomech. Eng."},{"issue":"2","key":"2022110901082358900_bib26","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.jbiomech.2014.11.038","article-title":"Chronic Changes in the Articular Cartilage and Meniscus Following Traumatic Impact to the Lapine Knee","volume":"48","year":"2015","journal-title":"J. Biomech."},{"issue":"6","key":"2022110901082358900_bib27","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1111\/vsu.13643","article-title":"Reconstruction of the Cranial Cruciate Ligament Using a Semitendinosus Autograft in a Lapine Model","volume":"50","year":"2021","journal-title":"Vet. Surg."},{"issue":"2","key":"2022110901082358900_bib28","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.jss.2009.03.006","article-title":"Traumatic Anterior Cruciate Ligament Tear and Its Implications on Meniscal Degradation: A Preliminary Novel Lapine Osteoarthritis Model","volume":"164","year":"2010","journal-title":"J. Surg. Res."},{"issue":"4","key":"2022110901082358900_bib29","first-page":"382","article-title":"Osseous Injury Associated With Acute Tears of the Anterior Cruciate Ligament","volume":"20","year":"1992","journal-title":"Am. J"},{"issue":"4","key":"2022110901082358900_bib30","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1177\/036354659302100412","article-title":"Prospective Study of Osseous, Articular, and Meniscal Lesions in Recent Anterior Cruciate Ligament Tears by Magnetic Resonance Imaging and Arthroscopy","volume":"21","year":"1993","journal-title":"Am. J. Sports Med."},{"issue":"12","key":"2022110901082358900_bib31","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1002\/jor.22975","article-title":"Assessment of Cortical and Trabecular Bone Changes in Two Models of Post-Traumatic Osteoarthritis","volume":"33","year":"2015","journal-title":"J. Orthop. Res."},{"key":"2022110901082358900_bib32","first-page":"1","article-title":"A Novel Lapine Model of Closed-Joint Knee Injury With Post-Traumatic ACL Reconstruction and Meniscal Debridement","volume-title":"World Congress of Biomechanics","year":"2018"},{"issue":"2\u20133","key":"2022110901082358900_bib33","first-page":"133","article-title":"Treatment With the Non-Ionic Surfactant Poloxamer P188 Reduces DNA Fragmentation in Cells From Bovine Chondral Explants Exposed to Injurious Unconfined Compression","volume":"5","year":"2006","journal-title":"Biomech. Model. Mechanobiol."},{"issue":"9","key":"2022110901082358900_bib34","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.joca.2011.05.008","article-title":"Macroscopic and Histopathologic Analysis of Human Knee Menisci in Aging and Osteoarthritis","volume":"19","year":"2011","journal-title":"Osteoarthritis Cartilage"},{"issue":"2","key":"2022110901082358900_bib35","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/art.20027","article-title":"Analysis of Cartilage Biomarkers in the Early Phases of Canine Experimental Osteoarthritis","volume":"50","year":"2004","journal-title":"Arthritis Rheum."},{"issue":"1","key":"2022110901082358900_bib36","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/jor.1100160121","article-title":"Effect of Combined Axial Compressive and Anterior Tibial Loads on In Situ Forces in the Anterior Cruciate Ligament: A Porcine Study","volume":"16","year":"1998","journal-title":"J. Orthop. Res."},{"issue":"4","key":"2022110901082358900_bib37","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.knee.2011.07.005","article-title":"A Comparative Anatomical Study of the Human Knee and Six Animal Species","volume":"19","year":"2012","journal-title":"Knee"},{"issue":"5","key":"2022110901082358900_bib38","first-page":"1690","article-title":"Injections of Joints and Soft Tissue:Part II. Guidelines for Specific Joints","volume":"44","year":"1991","journal-title":"Am. Family Phys."},{"issue":"8","key":"2022110901082358900_bib39","first-page":"971","article-title":"Musculoskeletal Injections: A Review of the Evidence","volume":"78","year":"2008","journal-title":"Am. Family Phys."},{"issue":"7","key":"2022110901082358900_bib40","first-page":"1307","article-title":"Role of Interleukin 6 (IL-6)\/IL-6R-Induced Signal Tranducers and Activators of Transcription and Mitogen-Activated Protein Kinase\/Extracellular","volume":"32","year":"2005","journal-title":"J. Rheumot."},{"issue":"5","key":"2022110901082358900_bib41","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/jor.1100180510","article-title":"Comparison of Biomechanical and Biochemical Properties of Cartilage From Human Knee and Ankle Pairs","volume":"18","year":"2000","journal-title":"J. Orthop. Res."},{"issue":"2","key":"2022110901082358900_bib42","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.joca.2009.09.003","article-title":"Contrast Enhanced Computed Tomography Can Predict the Glycosaminoglycan Content and Biomechanical Properties of Articular Cartilage","volume":"18","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"issue":"6","key":"2022110901082358900_bib43","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1152\/japplphysiol.00848.2011","article-title":"Regional Variation in the Mechanical Role of Knee Meniscus Glycosaminoglycans","volume":"111","year":"2011","journal-title":"J. Appl. Physiol."},{"issue":"1","key":"2022110901082358900_bib44","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1115\/1.3138202","article-title":"Biphasic Creep and Stress Relaxation of Articular Cartilage in Compression: Theory and Experiments","volume":"102","year":"1980","journal-title":"ASME J. Biomech. Eng."},{"issue":"6","key":"2022110901082358900_bib45","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/jor.1100070602","article-title":"Material Properties of the Normal Medial Bovine Meniscus","volume":"7","year":"1989","journal-title":"J. Orthop. Res."},{"issue":"7","key":"2022110901082358900_bib46","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1002\/jor.20573","article-title":"Compressive Moduli of the Human Medial Meniscus in the Axial and Radial Directions at Equilibrium and at a Physiological Strain Rate","volume":"26","year":"2008","journal-title":"J. Orthop. Res."},{"issue":"3","key":"2022110901082358900_bib47","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1053\/joca.1998.0187","article-title":"Osteophytes in Osteoarthritis. Clinical Aspects","volume":"7","year":"1999","journal-title":"Osteoarthritis Cartilage"},{"issue":"2","key":"2022110901082358900_bib48","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/jor.22509","article-title":"Joint Instability and Cartilage Compression in a Mouse Model of Posttraumatic Osteoarthritis","volume":"32","year":"2014","journal-title":"J. Orthop. Res."},{"issue":"3","key":"2022110901082358900_bib49","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/jor.23252","article-title":"Osteophyte Formation After ACL Rupture in Mice is Associated With Joint Restabilization and Loss of Range of Motion","volume":"35","year":"2017","journal-title":"J. Orthop. Res."}],"container-title":["Journal of Biomechanical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/asmedigitalcollection.asme.org\/biomechanical\/article-pdf\/144\/4\/041003\/6787086\/bio_144_04_041003.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/asmedigitalcollection.asme.org\/biomechanical\/article-pdf\/144\/4\/041003\/6787086\/bio_144_04_041003.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T01:09:04Z","timestamp":1667956144000},"score":1,"resource":{"primary":{"URL":"https:\/\/asmedigitalcollection.asme.org\/biomechanical\/article\/144\/4\/041003\/1120716\/Evaluating-the-Efficacy-of-Combined-P188-Treatment"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,9]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4,1]]}},"URL":"https:\/\/doi.org\/10.1115\/1.4052564","relation":{},"ISSN":["0148-0731","1528-8951"],"issn-type":[{"value":"0148-0731","type":"print"},{"value":"1528-8951","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,9]]},"article-number":"041003"}}