{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:42:00Z","timestamp":1787020920755,"version":"build-2736575974"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:00:00Z","timestamp":1540339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:00:00Z","timestamp":1540339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"INFRAESTRUCTURA CONACYT 2016","award":["270485"],"award-info":[{"award-number":["270485"]}]},{"name":"FOSISS CONACYT 2016","award":["272792"],"award-info":[{"award-number":["272792"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Med Res"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A promising novel cell-free bioactive formulation for articular cartilage regeneration, called BIOF2, has recently been tested in pre-clinical trials. The aim of the present study was to evaluate the efficacy and safety of BIOF2 for intra-articular application in patients with severe osteoarthritis of the knee.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A prospective, randomized, 3-arm, parallel group clinical trial was conducted. It included 24 patients with severe osteoarthritis of the knee (WOMAC score 65.9\u2009\u00b1\u200917). Before they entered the study, all the patients were under osteoarthritis control through the standard treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed by their family physician. Patients were distributed into three groups of 8 patients each (intra-articular BIOF2, total joint arthroplasty, or conservative treatment with NSAIDs alone). The WOMAC score, RAPID3 score, and Rasmussen clinical score were evaluated before treatment and at months 3, 6, and 12. BIOF2 was applied at months 0, 3, and 6. Complete blood count and blood chemistry parameters were determined in the BIOF2 group before treatment, at 72\u00a0h, and at months 1, 3, 6, and 12. In addition, articular cartilage volume was evaluated (according to MRI) at the beginning of the study and at month 12.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The NSAID group showed no improvement at follow-up. Arthroplasty and BIOF2 treatments showed significant improvement in all the scoring scales starting at month 3. There were no statistically significant differences between the BIOF2 group and the arthroplasty group at month 6 (WOMAC score: 19.3\u2009\u00b1\u200918 vs 4.3\u2009\u00b1\u20095;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.24) or month 12 (WOMAC score: 15.6\u2009\u00b1\u200915 vs 15.7\u2009\u00b1\u200917;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20091.0). Arthroplasty and BIOF2 were successful at month 12 (according to a WOMAC score:\u2009\u2264\u200916) in 75% of the patients and the daily use of NSAIDs was reduced, compared with the group treated exclusively with NSAIDs (RR\u2009=\u20090.33, 95% CI 0.12\u20130.87,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.02. This result was the same for BIOF2 vs NSAIDs and arthroplasty vs NSAIDs). BIOF2 significantly increased the articular cartilage by 22% (26.1\u2009\u00b1\u200910 vs 31.9\u2009\u00b1\u200910 cm\n                      <jats:sup>2<\/jats:sup>\n                      ,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) and produced a significant reduction in serum lipids. BIOF2 was well tolerated, causing slight-to-moderate pain only upon application.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The intra-articular application of the new bioactive cell-free formulation (BIOF2) was well tolerated and showed no significative differences with arthroplasty for the treatment of severe osteoarthritis of the knee. BIOF2 can regenerate articular cartilage and is an easily implemented alternative therapy for the treatment of osteoarthritis.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial registration<\/jats:italic>\n                      Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000250. Registered 08\/15\/2017\u2014Retrospectively registered,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/rpcec.sld.cu\/en\/trials\/RPCEC00000250-En\">http:\/\/rpcec.sld.cu\/en\/trials\/RPCEC00000250-En<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40001-018-0349-2","type":"journal-article","created":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:54:48Z","timestamp":1540342488000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A phase I\u2013II controlled randomized trial using a promising novel cell-free formulation for articular cartilage regeneration as treatment of severe osteoarthritis of the knee"],"prefix":"10.1186","volume":"23","clinical-trial-number":[{"clinical-trial-number":"rpcec00000250","registry":"10.18810\/rpec"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9848-862X","authenticated-orcid":false,"given":"Ivan","family":"Delgado-Enciso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Paz-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Valtierra-Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Preciado-Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Almeida-Trinidad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Guzman-Esquivel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha A.","family":"Mendoza-Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Garcia-Vega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro D.","family":"Soriano-Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Cortes-Bazan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector R.","family":"Galvan-Salazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariana","family":"Cabrera-Licona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iram P.","family":"Rodriguez-Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita L.","family":"Martinez-Fierro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josuel","family":"Delgado-Enciso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Paz-Michel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,24]]},"reference":[{"key":"349_CR1","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.jcot.2016.05.005","volume":"7","author":"R Vaishya","year":"2016","unstructured":"Vaishya R, Pariyo GB, Agarwal AK, Vijay V. Non-operative management of osteoarthritis of the knee joint. J Clin Orthop Trauma. 2016;7:170\u20136.","journal-title":"J Clin Orthop Trauma"},{"key":"349_CR2","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/bmb\/lds038","volume":"105","author":"A Litwic","year":"2013","unstructured":"Litwic A, Edwards MH, Dennison EM, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull. 2013;105:185\u201399.","journal-title":"Br Med Bull"},{"key":"349_CR3","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1016\/j.joca.2016.07.017","volume":"24","author":"MA Karsdal","year":"2016","unstructured":"Karsdal MA, Michaelis M, Ladel C, Siebuhr AS, Bihlet AR, Andersen JR, et al. Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future. Osteoarthr Cartil. 2016;24:2013\u201321.","journal-title":"Osteoarthr Cartil"},{"key":"349_CR4","doi-asserted-by":"publisher","DOI":"10.4137\/CMAMD.S17894","author":"SA Raeissadat","year":"2015","unstructured":"Raeissadat SA, Rayegani SM, Hassanabadi H, Fathi M, Ghorbani E, Babaee M, et al. Knee osteoarthritis injection choices: platelet-rich plasma (PRP) versus hyaluronic acid (a one-year randomized clinical trial). Clin Med Insights Arthritis Musculoskelet Disord. 2015. https:\/\/doi.org\/10.4137\/CMAMD.S17894.","journal-title":"Clin Med Insights Arthritis Musculoskelet Disord"},{"key":"349_CR5","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2105\/AJPH.84.3.351","volume":"84","author":"AA Guccione","year":"1994","unstructured":"Guccione AA, Felson DT, Anderson JJ, Anthony JM, Zhang Y, Wilson PWF, et al. The effects of specific medical conditions on the functional limitations of elders in the Framingham study. Am J Public Health. 1994;84:351\u20138.","journal-title":"Am J Public Health"},{"key":"349_CR6","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.amjms.2017.06.006","volume":"355","author":"Z Meng","year":"2018","unstructured":"Meng Z, Huang R. Topical treatment of degenerative knee osteoarthritis. Am J Med Sci. 2018;355:6\u201312.","journal-title":"Am J Med Sci"},{"key":"349_CR7","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1002\/art.1780380613","volume":"38","author":"EF Philbin","year":"1995","unstructured":"Philbin EF, Groff GD, Ries MD, Miller TE. Cardiovascular fitness and health in patients with end-stage osteoarthritis. Arthritis Rheum. 1995;38:799\u2013805.","journal-title":"Arthritis Rheum"},{"key":"349_CR8","doi-asserted-by":"crossref","unstructured":"Schiphof D, van den Driest JJ, Runhaar J. Osteoarthritis year in review 2017: rehabilitation and outcomes. Osteoarthr Cartil [Internet]. W.B. Saunders; 2018. https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1063458418300189?via%3Dihub. Accessed 24 Jan 2018.","DOI":"10.1016\/j.joca.2018.01.006"},{"key":"349_CR9","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.1016\/j.joca.2016.07.010","volume":"24","author":"RR Bannuru","year":"2016","unstructured":"Bannuru RR, Osani M, Vaysbrot EE, McAlindon TE. Comparative safety profile of hyaluronic acid products for knee osteoarthritis: a systematic review and network meta-analysis. Osteoarthr Cartil. 2016;24:2022\u201341.","journal-title":"Osteoarthr Cartil"},{"key":"349_CR10","first-page":"207","volume":"81","author":"C Herrera-Espineira","year":"2013","unstructured":"Herrera-Espineira C, Escobar A, Navarro-Espigares JL, de Castillo J de DL, Garcia-Perez L, Godoy-Montijano A. Total knee and hip prosthesis: variables associated with costs. Cir Cir. 2013;81:207\u201313.","journal-title":"Cir Cir"},{"key":"349_CR11","doi-asserted-by":"publisher","first-page":"15040","DOI":"10.1038\/boneres.2015.40","volume":"4","author":"W Zhang","year":"2016","unstructured":"Zhang W, Ouyang H, Dass CR, Xu J. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res. 2016;4:15040.","journal-title":"Bone Res"},{"key":"349_CR12","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1002\/art.37901","volume":"65","author":"GA Hawker","year":"2013","unstructured":"Hawker GA, Badley EM, Borkhoff CM, Croxford R, Davis AM, Dunn S, et al. Which patients are most likely to benefit from total joint arthroplasty? Arthritis Rheum. 2013;65:1243\u201352.","journal-title":"Arthritis Rheum"},{"key":"349_CR13","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1007\/s11420-012-9320-x","volume":"9","author":"EC Rodriguez-Merchan","year":"2013","unstructured":"Rodriguez-Merchan EC. Intra-articular injections of hyaluronic acid and other drugs in the knee joint. HSS J. 2013;9:180\u20132.","journal-title":"HSS J"},{"key":"349_CR14","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.3390\/ijms17071064","volume":"17","author":"E Monta\u00f1ez-Heredia","year":"2016","unstructured":"Monta\u00f1ez-Heredia E, Ir\u00edzar S, Huertas PJ, Otero E, Del Valle M, Prat I, et al. Intra-articular injections of platelet-rich plasma versus hyaluronic acid in the treatment of osteoarthritic knee pain: a randomized clinical trial in the context of the Spanish national health care system. Int J Mol Sci. 2016;17:1064.","journal-title":"Int J Mol Sci"},{"key":"349_CR15","doi-asserted-by":"publisher","first-page":"629","DOI":"10.4252\/wjsc.v6.i5.629","volume":"6","author":"K Uth","year":"2014","unstructured":"Uth K, Trifonov D. Stem cell application for osteoarthritis in the knee joint: a minireview. World J Stem Cells. 2014;6:629\u201336.","journal-title":"World J Stem Cells"},{"key":"349_CR16","unstructured":"Paz Garcia J, Paz Michel BA. Formulation for regeneration of bone, cartilage, teeth, and periodontium and treatment of tumors and cysts. United States Patents, US9089580B1 and US9433629B2."},{"key":"349_CR17","first-page":"3503","volume":"17","author":"I Delgado-Enciso","year":"2018","unstructured":"Delgado-Enciso I, Paz-Garcia J, Rodriguez-Hernandez A, Madrigal-Perez VM, Cabrera-Licona A, Garcia-Rivera A, et al. A promising novel formulation for articular cartilage regeneration: preclinical evaluation of a treatment that produces SOX9 overexpression in human synovial fluid cells. Mol Med Rep. 2018;17:3503\u201310.","journal-title":"Mol Med Rep"},{"key":"349_CR18","first-page":"1287","volume":"83","author":"E Ringdahl","year":"2011","unstructured":"Ringdahl E, Pandit S. Treatment of knee osteoarthritis. Am Fam Physician. 2011;83:1287\u201392.","journal-title":"Am Fam Physician"},{"key":"349_CR19","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.joca.2010.02.011","volume":"18","author":"TE McAlindon","year":"2010","unstructured":"McAlindon TE, Bannuru RR. OARSI recommendations for the management of hip and knee osteoarthritis: the semantics of differences and changes. Osteoarthr Cartil. 2010;18:473\u20135.","journal-title":"Osteoarthr Cartil"},{"key":"349_CR20","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1002\/acr.22390","volume":"66","author":"HMK Ghomrawi","year":"2014","unstructured":"Ghomrawi HMK, Alexiades M, Pavlov H, Nam D, Endo Y, Mandl LA, et al. Evaluation of two appropriateness criteria for total knee replacement. Arthritis Care Res. 2014;66:1749\u201353.","journal-title":"Arthritis Care Res"},{"key":"349_CR21","doi-asserted-by":"publisher","first-page":"2154","DOI":"10.1016\/j.arth.2015.06.012","volume":"30","author":"JM Giesinger","year":"2015","unstructured":"Giesinger JM, Hamilton DF, Jost B, Behrend H, Giesinger K. WOMAC, EQ-5D and knee society score thresholds for treatment success after total knee arthroplasty. J Arthroplasty. 2015;30:2154\u20138.","journal-title":"J Arthroplasty"},{"key":"349_CR22","first-page":"23","volume":"VIII","author":"G Cuenca","year":"2006","unstructured":"Cuenca G, Liset Y, Gonz\u00e1lez F, Jes\u00fas E, Boza R, Edith M, et al. Calidad de vida en pacientes con osteoartrosis de cadera y rodilla. Rev Cuba Reumatol. 2006;VIII:23\u201342.","journal-title":"Rev Cuba Reumatol"},{"key":"349_CR23","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1097\/RHU.0b013e3182936b98","volume":"19","author":"I Castrej\u00f3n","year":"2013","unstructured":"Castrej\u00f3n I, Bergman MJ, Pincus T. MDHAQ\/RAPID3 to recognize improvement over 2\u00a0months in usual care of patients with osteoarthritis, systemic lupus erythematosus, spondyloarthropathy, and gout, as well as rheumatoid arthritis. J Clin Rheumatol. 2013;19:169\u201374.","journal-title":"J Clin Rheumatol"},{"key":"349_CR24","doi-asserted-by":"publisher","first-page":"e000391","DOI":"10.1136\/rmdopen-2016-000391","volume":"3","author":"C El-Haddad","year":"2017","unstructured":"El-Haddad C, Castrejon I, Gibson KA, Yazici Y, Bergman MJ, Pincus T. MDHAQ\/RAPID3 scores in patients with osteoarthritis are similar to or higher than in patients with rheumatoid arthritis: a cross-sectional study from current routine rheumatology care at four sites. RMD Open. 2017;3:e000391.","journal-title":"RMD Open"},{"key":"349_CR25","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s11751-012-0148-1","volume":"7","author":"C Dall\u2019Oca","year":"2012","unstructured":"Dall\u2019Oca C, Maluta T, Lavini F, Bondi M, Micheloni GM, Bartolozzi P. Tibial plateau fractures: compared outcomes between ARIF and ORIF. Strateg Trauma Limb Reconstr. 2012;7:163\u201375.","journal-title":"Strateg Trauma Limb Reconstr"},{"key":"349_CR26","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1002\/art.20000","volume":"50","author":"J-P Raynauld","year":"2004","unstructured":"Raynauld J-P, Martel-Pelletier J, Berthiaume M-J, Labont\u00e9 F, Beaudoin G, de Guise JA, et al. Quantitative magnetic resonance imaging evaluation of knee osteoarthritis progression over two years and correlation with clinical symptoms and radiologic changes. Arthritis Rheum. 2004;50:476\u201387.","journal-title":"Arthritis Rheum"},{"key":"349_CR27","doi-asserted-by":"publisher","first-page":"2280","DOI":"10.1242\/dev.096354","volume":"140","author":"Y Sugimoto","year":"2013","unstructured":"Sugimoto Y, Takimoto A, Akiyama H, Kist R, Scherer G, Nakamura T, et al. Scx\u2009+\/Sox9\u2009+\u2009progenitors contribute to the establishment of the junction between cartilage and tendon\/ligament. Development. 2013;140:2280\u20138.","journal-title":"Development"},{"key":"349_CR28","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/8792","volume":"22","author":"W Bi","year":"1999","unstructured":"Bi W, Deng JM, Zhang Z, Behringer RR, De Crombrugghe B. Sox9 is required for cartilage formation. Nat Genet. 1999;22:85\u20139.","journal-title":"Nat Genet"},{"key":"349_CR29","first-page":"256","volume":"16","author":"F De Ceuninck","year":"2005","unstructured":"De Ceuninck F, Marcheteau E, Berger S, Caliez A, Dumont V, Raes M, et al. Assessment of some tools for the characterization of the human osteoarthritic cartilage proteome. J Biomol Tech. 2005;16:256\u201365.","journal-title":"J Biomol Tech"},{"key":"349_CR30","doi-asserted-by":"publisher","first-page":"3151","DOI":"10.3390\/nu5083151","volume":"5","author":"M Akiyama","year":"2013","unstructured":"Akiyama M, Nakahama KI, Morita I. Impact of docosahexaenoic acid on gene expression during osteoclastogenesis in vitro-A comprehensive analysis. Nutrients. 2013;5:3151\u201362.","journal-title":"Nutrients"},{"key":"349_CR31","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1038\/nrd.2017.27","volume":"16","author":"M Cully","year":"2017","unstructured":"Cully M. Bone diseases: MST1R inhibitor prevents bone osteolysis. Nat Rev Drug Discov. 2017;16:164\u20135.","journal-title":"Nat Rev Drug Discov"},{"key":"349_CR32","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1080\/0886022X.2016.1216708","volume":"38","author":"J Yaxley","year":"2016","unstructured":"Yaxley J, Litfin T. Non-steroidal anti-inflammatories and the development of analgesic nephropathy: a systematic review. Ren Fail. 2016;38:1328\u201334.","journal-title":"Ren Fail"},{"key":"349_CR33","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1002\/stem.2475","volume":"35","author":"TS de Windt","year":"2017","unstructured":"de Windt TS, Vonk LA, Slaper-Cortenbach ICM, van den Broek MPH, Nizak R, van Rijen MHP, et al. Allogeneic mesenchymal stem cells stimulate cartilage regeneration and are safe for single-stage cartilage repair in humans upon mixture with recycled autologous chondrons. Stem Cells. 2017;35:256\u201364.","journal-title":"Stem Cells"},{"key":"349_CR34","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.knee.2015.08.013","volume":"23","author":"R Soler","year":"2016","unstructured":"Soler R, Orozco L, Munar A, Huguet M, L\u00f3pez R, Vives J, et al. Final results of a phase I\u2013II trial using ex vivo expanded autologous Mesenchymal Stromal Cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration. Knee. 2016;23:647\u201354.","journal-title":"Knee"},{"key":"349_CR35","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.arthro.2010.11.054","volume":"27","author":"K-Y Saw","year":"2011","unstructured":"Saw K-Y, Anz A, Merican S, Tay Y-G, Ragavanaidu K, Jee CSY, et al. Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology. Arthroscopy. 2011;27:493\u2013506.","journal-title":"Arthroscopy"},{"key":"349_CR36","first-page":"3833","volume":"19","author":"Y Li","year":"2015","unstructured":"Li Y, Tang J, Hu Y, Peng Y-H, Wang J-W. A study of autologous stem cells therapy assisted regeneration of cartilage in avascular bone necrosis. Eur Rev Med Pharmacol Sci. 2015;19:3833\u20137.","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"349_CR37","first-page":"135","volume":"11","author":"N Nandeesh","year":"2016","unstructured":"Nandeesh N, Janardhan K, Subramanian V, Ashtekar A, Srikruthi N, Koka P, et al. Treatment of AVN using autologous BM stem cells and activated platelet-derived growth factor concentrates. J Stem Cells. 2016;11:135\u201348.","journal-title":"J Stem Cells"},{"key":"349_CR38","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1177\/0363546510392711","volume":"39","author":"E Kon","year":"2011","unstructured":"Kon E, Delcogliano M, Filardo G, Busacca M, Di Martino A, Marcacci M. Novel nano-composite multilayered biomaterial for osteochondral regeneration: a pilot clinical trial. Am J Sports Med. 2011;39:1180\u201390.","journal-title":"Am J Sports Med"},{"key":"349_CR39","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009688","author":"K Pelttari","year":"2014","unstructured":"Pelttari K, Pippenger B, Mumme M, Feliciano S, Scotti C, Mainil-Varlet P, et al. Adult human neural crest-derived cells for articular cartilage repair. Sci Transl Med. 2014. https:\/\/doi.org\/10.1126\/scitranslmed.3009688.","journal-title":"Sci Transl Med"},{"key":"349_CR40","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1111\/j.1365-2648.2006.04102.x","volume":"57","author":"T-J Wang","year":"2007","unstructured":"Wang T-J, Belza B, Elaine Thompson F, Whitney JD, Bennett K. Effects of aquatic exercise on flexibility, strength and aerobic fitness in adults with osteoarthritis of the hip or knee. J Adv Nurs. 2007;57:141\u201352.","journal-title":"J Adv Nurs"}],"container-title":["European Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-018-0349-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40001-018-0349-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40001-018-0349-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,4]],"date-time":"2022-09-04T10:34:43Z","timestamp":1662287683000},"score":1,"resource":{"primary":{"URL":"https:\/\/eurjmedres.biomedcentral.com\/articles\/10.1186\/s40001-018-0349-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,24]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["349"],"URL":"https:\/\/doi.org\/10.1186\/s40001-018-0349-2","relation":{},"ISSN":["2047-783X"],"issn-type":[{"value":"2047-783X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,24]]},"assertion":[{"value":"16 March 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"52"}}