{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:39:34Z","timestamp":1792805974703,"version":"4.5.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T00:00:00Z","timestamp":1490572800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T00:00:00Z","timestamp":1490572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Microfracture of cartilage defects may induce alterations of the subchondral bone in the mid- and long-term, yet very little is known about their onset. Possibly, these changes may be avoided by an enhanced microfracture technique with additional application of bone marrow aspirate. In this study, full-thickness chondral defects in the knee joints of minipigs were either treated with (1) debridement down to the subchondral bone plate alone, (2) debridement with microfracture, or (3) microfracture with additional application of bone marrow aspirate. At 4 weeks after microfracture, the loss of subchondral bone below the defects largely exceeded the original microfracture holes. Of note, a significant increase of osteoclast density was identified in defects treated with microfracture alone compared with debridement only. Both changes were significantly counteracted by the adjunct treatment with bone marrow. Debridement and microfracture without or with bone marrow were equivalent regarding the early cartilage repair. These data suggest that microfracture induced a substantial early resorption of the subchondral bone and also highlight the potential value of bone marrow aspirate as an adjunct to counteract these alterations. Clinical studies are warranted to further elucidate early events of osteochondral repair and the effect of enhanced microfracture techniques.<\/jats:p>","DOI":"10.1038\/srep45189","type":"journal-article","created":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T09:58:51Z","timestamp":1490608731000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair"],"prefix":"10.1038","volume":"7","author":[{"given":"Liang","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Orth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"M\u00fcller-Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars K. H.","family":"Goebel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Cucchiarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Madry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,27]]},"reference":[{"key":"BFsrep45189_CR1","first-page":"2470","volume":"92A","author":"AH Gomoll","year":"2010","unstructured":"Gomoll, A. H., Farr, J., Gillogly, S. D., Kercher, J. & Minas, T. Surgical Management of Articular Cartilage Defects of the Knee. J. Bone Joint Surg. Am. 92A, 2470\u20132490 (2010).","journal-title":"J. Bone Joint Surg. Am"},{"key":"BFsrep45189_CR2","doi-asserted-by":"crossref","unstructured":"Steadman, J. R., Rodkey, W. G. & Rodrigo, J. J. Microfracture: surgical technique and rehabilitation to treat chondral defects. Clin. Orthop. Relat. Res., S362\u2013369 (2001).","DOI":"10.1097\/00003086-200110001-00033"},{"key":"BFsrep45189_CR3","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1053\/j.oto.2014.02.003","volume":"24","author":"C Erggelet","year":"2014","unstructured":"Erggelet, C. Enhanced Marrow Stimulation Techniques for Cartilage Repair. Oper. Tech. Orthop. 24, 2\u201313 (2014).","journal-title":"Oper. Tech. Orthop"},{"key":"BFsrep45189_CR4","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.2106\/JBJS.I.01284","volume":"92","author":"LA Fortier","year":"2010","unstructured":"Fortier, L. A. et al. Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J. Bone Joint Surg. Am. 92, 1927\u20131937 (2010).","journal-title":"J. Bone Joint Surg. Am"},{"key":"BFsrep45189_CR5","doi-asserted-by":"publisher","first-page":"2671","DOI":"10.2106\/JBJS.D.02536","volume":"87A","author":"CD Hoemann","year":"2005","unstructured":"Hoemann, C. D. et al. Chitosan-glycerol phosphate\/blood implants improve hyaline cartilage repair in ovine microfracture defects. J. Bone Joint Surg. Am. 87A, 2671\u20132686 (2005).","journal-title":"J. Bone Joint Surg. Am"},{"key":"BFsrep45189_CR6","doi-asserted-by":"publisher","first-page":"e71602","DOI":"10.1371\/journal.pone.0071602","volume":"8","author":"M Betsch","year":"2013","unstructured":"Betsch, M. et al. Bone marrow aspiration concentrate and platelet rich plasma for osteochondral repair in a porcine osteochondral defect model. PLoS One 8, e71602 (2013).","journal-title":"PLoS One"},{"key":"BFsrep45189_CR7","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.knee.2014.10.003","volume":"22","author":"D Enea","year":"2015","unstructured":"Enea, D. et al. One-step cartilage repair in the knee: Collagen-covered microfracture and autologous bone marrow concentrate. A pilot study. Knee 22, 30\u201335 (2015).","journal-title":"Knee"},{"key":"BFsrep45189_CR8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1177\/03946320110241S213","volume":"24","author":"A Gigante","year":"2011","unstructured":"Gigante, A. et al. Use of Collagen Scaffold and Autologous Bone Marrow Concentrate as a One-Step Cartilage Repair in the Knee: Histological Results of Second-Look Biopsies at 1 Year Follow-Up. Int. J. Immunopathol. Pharmacol. 24, 69\u201372 (2011).","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"BFsrep45189_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/BOT.0000000000000453","volume":"30","author":"A Gianakos","year":"2016","unstructured":"Gianakos, A., Ni, A., Zambrana, L., Kennedy, J. G. & Lane, J. M. Bone Marrow Aspirate Concentrate in Animal Long Bone Healing: An Analysis of Basic Science Evidence. J. Orthop. Trauma 30, 1\u20139 (2016).","journal-title":"J. Orthop. Trauma"},{"key":"BFsrep45189_CR10","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/s12891-015-0649-4","volume":"16","author":"H Weel","year":"2015","unstructured":"Weel, H. et al. The effect of concentrated bone marrow aspirate in operative treatment of fifth metatarsal stress fractures; a double-blind randomized controlled trial. BMC Musculoskelet. Disord. 16, 211 (2015).","journal-title":"BMC Musculoskelet. Disord."},{"key":"BFsrep45189_CR11","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1007\/s00167-010-1072-x","volume":"18","author":"AH Gomoll","year":"2010","unstructured":"Gomoll, A. H. et al. The subchondral bone in articular cartilage repair: current problems in the surgical management. Knee Surg. Sports Traumatol. Arthrosc. 18, 434\u2013447 (2010).","journal-title":"Knee Surg. Sports Traumatol. Arthrosc"},{"key":"BFsrep45189_CR12","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1055\/s-0032-1319782","volume":"25","author":"CD Hoemann","year":"2012","unstructured":"Hoemann, C. D., Lafantaisie-Favreau, C. H., Lascau-Coman, V., Chen, G. & Guzman-Morales, J. The cartilage-bone interface. J. Knee Surg. 25, 85\u201397 (2012).","journal-title":"J. Knee Surg"},{"key":"BFsrep45189_CR13","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s00167-010-1054-z","volume":"18","author":"H Madry","year":"2010","unstructured":"Madry, H., van Dijk, C. N. & Mueller-Gerbl, M. The basic science of the subchondral bone. Knee Surg. Sports Traumatol. Arthrosc. 18, 419\u2013433 (2010).","journal-title":"Knee Surg. Sports Traumatol. Arthrosc"},{"key":"BFsrep45189_CR14","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1097\/00002142-199906000-00002","volume":"10","author":"H Imhof","year":"1999","unstructured":"Imhof, H., Breitenseher, M., Kainberger, F., Rand, T. & Trattnig, S. Importance of subchondral bone to articular cartilage in health and disease. Top. Magn. Reson. Imaging 10, 180\u2013192 (1999).","journal-title":"Top. Magn. Reson. Imaging"},{"key":"BFsrep45189_CR15","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1097\/00004424-200010000-00004","volume":"35","author":"H Imhof","year":"2000","unstructured":"Imhof, H. et al. Subchondral bone and cartilage disease: a rediscovered functional unit. Invest. Radiol. 35, 581\u2013588 (2000).","journal-title":"Invest. Radiol."},{"key":"BFsrep45189_CR16","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1177\/0363546511399382","volume":"39","author":"BJ Cole","year":"2011","unstructured":"Cole, B. J. et al. Outcomes After a Single-Stage Procedure for Cell-Based Cartilage Repair A Prospective Clinical Safety Trial With 2-year Follow-up. Am. J. Sports Med. 39, 1170\u20131179 (2011).","journal-title":"Am. J. Sports Med."},{"key":"BFsrep45189_CR17","doi-asserted-by":"publisher","first-page":"299","DOI":"10.22203\/eCM.v025a21","volume":"25","author":"P Orth","year":"2013","unstructured":"Orth, P., Cucchiarini, M., Kohn, D. & Madry, H. Alterations of the subchondral bone in osteochondral repair\u2013translational data and clinical evidence. Eur. Cell. Mater. 25, 299\u2013316 (2013).","journal-title":"Eur. Cell. Mater"},{"key":"BFsrep45189_CR18","doi-asserted-by":"publisher","first-page":"10S","DOI":"10.1177\/0363546509350694","volume":"37","author":"DB Saris","year":"2009","unstructured":"Saris, D. B. et al. Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am. J. Sports Med. 37, 10S\u201319S (2009).","journal-title":"Am. J. Sports Med."},{"key":"BFsrep45189_CR19","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1177\/0363546511403282","volume":"39","author":"H Chen","year":"2011","unstructured":"Chen, H. et al. Characterization of subchondral bone repair for marrow-stimulated chondral defects and its relationship to articular cartilage resurfacing. Am. J. Sports Med. 39, 1731\u20131740 (2011).","journal-title":"Am. J. Sports Med."},{"key":"BFsrep45189_CR20","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1177\/0363546506289882","volume":"34","author":"DD Frisbie","year":"2006","unstructured":"Frisbie, D. D. et al. Effects of calcified cartilage on healing of chondral defects treated with microfracture in horses. Am. J. Sports Med. 34, 1824\u20131831 (2006).","journal-title":"Am. J. Sports Med."},{"key":"BFsrep45189_CR21","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1302\/0301-620X.92B3.22558","volume":"92","author":"M Drobnic","year":"2010","unstructured":"Drobnic, M., Radosavljevic, D., Cor, A., Brittberg, M. & Strazar, K. Debridement of cartilage lesions before autologous chondrocyte implantation by open or transarthroscopic techniques: a comparative study using post-mortem materials. J. Bone Joint Surg. Br. 92, 602\u2013608 (2010).","journal-title":"J. Bone Joint Surg. Br"},{"key":"BFsrep45189_CR22","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1177\/1947603510381096","volume":"2","author":"G Chen","year":"2011","unstructured":"Chen, G. et al. Acute Osteoclast Activity following Subchondral Drilling Is Promoted by Chitosan and Associated with Improved Cartilage Repair Tissue Integration. Cartilage 2, 173\u2013185 (2011).","journal-title":"Cartilage"},{"key":"BFsrep45189_CR23","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1016\/j.joca.2012.05.010","volume":"20","author":"L Goebel","year":"2012","unstructured":"Goebel, L. et al. Experimental scoring systems for macroscopic articular cartilage repair correlate with the MOCART score assessed by a high-field MRI at 9.4 T\u2013comparative evaluation of five macroscopic scoring systems in a large animal cartilage defect model. Osteoarthritis Cartilage 20, 1046\u20131055 (2012).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep45189_CR24","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.2106\/00004623-199710000-00002","volume":"79","author":"RS Sellers","year":"1997","unstructured":"Sellers, R. S., Peluso, D. & Morris, E. A. The effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the healing of full-thickness defects of articular cartilage. J. Bone Joint Surg. Am. 79, 1452\u20131463 (1997).","journal-title":"J. Bone Joint Surg. Am"},{"key":"BFsrep45189_CR25","doi-asserted-by":"publisher","first-page":"32982","DOI":"10.1038\/srep32982","volume":"6","author":"L Gao","year":"2016","unstructured":"Gao, L., Orth, P., Goebel, L. K. H., Cucchiarini, M. & Madry, H. A novel algorithm for a precise analysis of subchondral bone alterations. Sci. Rep. 6, 32982 (2016).","journal-title":"Sci. Rep"},{"key":"BFsrep45189_CR26","doi-asserted-by":"publisher","first-page":"684","DOI":"10.2106\/00004623-198971050-00007","volume":"71","author":"J Connolly","year":"1989","unstructured":"Connolly, J., Guse, R., Lippiello, L. & Dehne, R. Development of an Osteogenic Bone-Marrow Preparation. J. Bone Joint Surg. Am. 71, 684\u2013691 (1989).","journal-title":"J. Bone Joint Surg. Am"},{"key":"BFsrep45189_CR27","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.jcyt.2012.09.004","volume":"15","author":"JI Dawson","year":"2013","unstructured":"Dawson, J. I. et al. Enhancing the osteogenic efficacy of human bone marrow aspirate: concentrating osteoprogenitors using wave-assisted filtration. Cytotherapy 15, 242\u2013252 (2013).","journal-title":"Cytotherapy"},{"key":"BFsrep45189_CR28","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.knee.2013.04.003","volume":"20","author":"D Enea","year":"2013","unstructured":"Enea, D. et al. Single-stage cartilage repair in the knee with microfracture covered with a resorbable polymer-based matrix and autologous bone marrow concentrate. Knee 20, 562\u2013569 (2013).","journal-title":"Knee"},{"key":"BFsrep45189_CR29","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/0749-8063(91)90072-6","volume":"7","author":"LL Johnson","year":"1991","unstructured":"Johnson, L. L. Characteristics of the immediate postarthroscopic blood clot formation in the knee joint. Arthroscopy 7, 14\u201323 (1991).","journal-title":"Arthroscopy"},{"key":"BFsrep45189_CR30","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/S0749-8063(86)80012-3","volume":"2","author":"LL Johnson","year":"1986","unstructured":"Johnson, L. L. Arthroscopic abrasion arthroplasty historical and pathologic perspective: present status. Arthroscopy 2, 54\u201369 (1986).","journal-title":"Arthroscopy"},{"key":"BFsrep45189_CR31","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.arthro.2015.04.073","volume":"31","author":"LL Johnson","year":"2015","unstructured":"Johnson, L. L. & Spector, M. The New Microfracture: All Things Considered. Arthroscopy 31, 1028\u20131031 (2015).","journal-title":"Arthroscopy"},{"key":"BFsrep45189_CR32","doi-asserted-by":"crossref","unstructured":"Hernigou, P. & Beaujean, F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin. Orthop. Relat. Res., 14\u201323 (2002).","DOI":"10.1097\/00003086-200212000-00003"},{"key":"BFsrep45189_CR33","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1302\/0301-620X.87B7.16289","volume":"87","author":"P Hernigou","year":"2005","unstructured":"Hernigou, P., Poignard, A., Manicom, O., Mathieu, G. & Rouard, H. The use of percutaneous autologous bone marrow transplantation in nonunion and avascular necrosis of bone. J. Bone Joint Surg. Br. 87, 896\u2013902 (2005).","journal-title":"J. Bone Joint Surg. Br"},{"key":"BFsrep45189_CR34","doi-asserted-by":"publisher","first-page":"7","DOI":"10.2174\/1876893801304010007","volume":"4","author":"R Hauser","year":"2013","unstructured":"Hauser, R. & Eteshola, E. Rationale for Using Direct Bone Marrow Aspirate as a Proliferant for Re-generative Injection Therapy (Prolotherapy). Open Stem Cell J 4, 7\u201314 (2013).","journal-title":"Open Stem Cell J"},{"key":"BFsrep45189_CR35","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1111\/j.0959-9673.2005.00420.x","volume":"86","author":"M Abdel-Hamid","year":"2005","unstructured":"Abdel-Hamid, M., Hussein, M. R., Ahmad, A. F. & Elgezawi, E. M. Enhancement of the repair of meniscal wounds in the red-white zone (middle third) by the injection of bone marrow cells in canine animal model. Int. J. Exp. Pathol. 86, 117\u2013123 (2005).","journal-title":"Int. J. Exp. Pathol"},{"key":"BFsrep45189_CR36","first-page":"260","volume":"76","author":"JP Benthien","year":"2010","unstructured":"Benthien, J. P. & Behrens, P. Autologous matrix-induced chondrogenesis (AMIC). A one-step procedure for retropatellar articular resurfacing. Acta Orthop. Belg. 76, 260\u2013263 (2010).","journal-title":"Acta Orthop. Belg."},{"key":"BFsrep45189_CR37","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1097\/JSA.0000000000000071","volume":"23","author":"AM Hirahara","year":"2015","unstructured":"Hirahara, A. M. & Mueller, K. W. Jr. BioCartilage: A New Biomaterial to Treat Chondral Lesions. Sports Med. Arthrosc. 23, 143\u2013148 (2015).","journal-title":"Sports Med. Arthrosc"},{"key":"BFsrep45189_CR38","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1177\/1947603515595837","volume":"7","author":"S Methot","year":"2016","unstructured":"Methot, S. et al. Osteochondral Biopsy Analysis Demonstrates That BST-CarGel Treatment Improves Structural and Cellular Characteristics of Cartilage Repair Tissue Compared With Microfracture. Cartilage 7, 16\u201328 (2016).","journal-title":"Cartilage"},{"key":"BFsrep45189_CR39","doi-asserted-by":"publisher","first-page":"e663","DOI":"10.1016\/j.eats.2015.07.008","volume":"4","author":"YRJ Vila","year":"2015","unstructured":"Vila, Y. R. J., Dalmau, A., Chaques, F. J. & Asuncion, J. Treatment of Osteochondral Lesions of the Talus With Bone Marrow Stimulation and Chitosan-Glycerol Phosphate\/Blood Implants (BST-CarGel). Arthrosc. Tech. 4, e663\u2013667 (2015).","journal-title":"Arthrosc. Tech"},{"key":"BFsrep45189_CR40","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s00402-012-1621-5","volume":"133","author":"J Gille","year":"2013","unstructured":"Gille, J. et al. Outcome of Autologous Matrix Induced Chondrogenesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch. Orthop. Trauma Surg. 133, 87\u201393 (2013).","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"BFsrep45189_CR41","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1007\/s00167-010-1042-3","volume":"18","author":"J Gille","year":"2010","unstructured":"Gille, J. et al. Mid-term results of Autologous Matrix-Induced Chondrogenesis for treatment of focal cartilage defects in the knee. Knee Surg. Sports Traumatol. Arthrosc. 18, 1456\u20131464 (2010).","journal-title":"Knee Surg. Sports Traumatol. Arthrosc"},{"key":"BFsrep45189_CR42","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.2106\/JBJS.L.01345","volume":"95","author":"WD Stanish","year":"2013","unstructured":"Stanish, W. D. et al. Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial. J. Bone Joint Surg. Am. 95, 1640\u20131650 (2013).","journal-title":"J. Bone Joint Surg. Am"},{"key":"BFsrep45189_CR43","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1002\/jor.20905","volume":"27","author":"HM Chen","year":"2009","unstructured":"Chen, H. M. et al. Drilling and Microfracture Lead to Different Bone Structure and Necrosis during Bone-Marrow Stimulation for Cartilage Repair. J. Orthop. Res. 27, 1432\u20131438 (2009).","journal-title":"J. Orthop. Res."},{"key":"BFsrep45189_CR44","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.joca.2006.05.003","volume":"14","author":"PC Kreuz","year":"2006","unstructured":"Kreuz, P. C. et al. Results after microfracture of full-thickness chondral defects in different compartments in the knee. Osteoarthritis Cartilage 14, 1119\u20131125 (2006).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep45189_CR45","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.2106\/00004623-200509000-00002","volume":"87","author":"K Mithoefer","year":"2005","unstructured":"Mithoefer, K. et al. The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study. J. Bone Joint Surg. Am. 87, 1911\u20131920 (2005).","journal-title":"J. Bone Joint Surg. Am"},{"key":"BFsrep45189_CR46","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.knee.2005.04.003","volume":"12","author":"IJ Henderson","year":"2005","unstructured":"Henderson, I. J. & La Valette, D. P. Subchondral bone overgrowth in the presence of full-thickness cartilage defects in the knee. Knee 12, 435\u2013440 (2005).","journal-title":"Knee"},{"key":"BFsrep45189_CR47","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1177\/0363546508330137","volume":"37","author":"T Minas","year":"2009","unstructured":"Minas, T., Gomoll, A. H., Rosenberger, R., Royce, R. O. & Bryant, T. Increased failure rate of autologous chondrocyte implantation after previous treatment with marrow stimulation techniques. Am. J. Sports Med. 37, 902\u2013908 (2009).","journal-title":"Am. J. Sports Med."},{"key":"BFsrep45189_CR48","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1177\/0363546509358266","volume":"38","author":"HS Vasiliadis","year":"2010","unstructured":"Vasiliadis, H. S. et al. Autologous chondrocyte implantation in cartilage lesions of the knee: long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique. Am. J. Sports Med. 38, 943\u2013949 (2010).","journal-title":"Am. J. Sports Med."},{"key":"BFsrep45189_CR49","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/jor.22521","volume":"32","author":"HT Kokkonen","year":"2014","unstructured":"Kokkonen, H. T. et al. In vivo diagnostics of human knee cartilage lesions using delayed CBCT arthrography. J. Orthop. Res. 32, 403\u2013412 (2014).","journal-title":"J. Orthop. Res."},{"key":"BFsrep45189_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40634-015-0031-3","volume":"2","author":"BB Christensen","year":"2015","unstructured":"Christensen, B. B. et al. Experimental articular cartilage repair in the G\u00f6ttingen minipig: the influence of multiple defects per knee. J. Exp. Orthop. 2, 1\u201311 (2015).","journal-title":"J. Exp. Orthop"},{"key":"BFsrep45189_CR51","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.proghi.2015.10.001","volume":"50","author":"P Orth","year":"2015","unstructured":"Orth, P., Peifer, C., Goebel, L., Cucchiarini, M. & Madry, H. Comprehensive analysis of translational osteochondral repair: Focus on the histological assessment. Prog. Histochem. Cytochem. 50, 19\u201336 (2015).","journal-title":"Prog. Histochem. Cytochem."},{"key":"BFsrep45189_CR52","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1089\/ten.tec.2012.0699","volume":"19","author":"P Orth","year":"2013","unstructured":"Orth, P., Zurakowski, D., Alini, M., Cucchiarini, M. & Madry, H. Reduction of sample size requirements by bilateral versus unilateral research designs in animal models for cartilage tissue engineering. Tissue Eng. Part C Methods 19, 885\u2013891 (2013).","journal-title":"Tissue Eng. Part C Methods"},{"key":"BFsrep45189_CR53","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/j.joca.2012.06.008","volume":"20","author":"P Orth","year":"2012","unstructured":"Orth, P. et al. Temporal and spatial migration pattern of the subchondral bone plate in a rabbit osteochondral defect model. Osteoarthritis Cartilage 20, 1161\u20131169 (2012).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep45189_CR54","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1177\/0363546515610507","volume":"44","author":"P Orth","year":"2016","unstructured":"Orth, P., Duffner, J., Zurakowski, D., Cucchiarini, M. & Madry, H. Small-Diameter Awls Improve Articular Cartilage Repair After Microfracture Treatment in a Translational Animal Model. Am. J. Sports Med. 44, 209\u2013219 (2016).","journal-title":"Am. J. Sports Med."},{"key":"BFsrep45189_CR55","first-page":"345","volume":"80","author":"RJ van \u2018t Hof","year":"2003","unstructured":"van \u2018t Hof, R. J., Clarkin, C. E. & Armour, K. J. Studies of local bone remodeling. The calvarial injection assay. Methods Mol. Med. 80, 345\u2013351 (2003).","journal-title":"Methods Mol. Med."},{"key":"BFsrep45189_CR56","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671\u2013675 (2012).","journal-title":"Nat. Methods"},{"key":"BFsrep45189_CR57","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1111\/j.1365-2559.2012.04333.x","volume":"61","author":"KP Egan","year":"2012","unstructured":"Egan, K. P., Brennan, T. A. & Pignolo, R. J. Bone histomorphometry using free and commonly available software. Histopathology 61, 1168\u20131173 (2012).","journal-title":"Histopathology"},{"key":"BFsrep45189_CR58","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1172\/JCI111096","volume":"72","author":"AM Parfitt","year":"1983","unstructured":"Parfitt, A. M. et al. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. J. Clin. Invest. 72, 1396\u20131409 (1983).","journal-title":"J. Clin. Invest"},{"key":"BFsrep45189_CR59","doi-asserted-by":"crossref","unstructured":"Haffner-Luntzer, M. et al. Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton. J. Orthop. Res., doi: 10.1002\/jor.23221 (2016).","DOI":"10.1002\/jor.23221"},{"key":"BFsrep45189_CR60","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1002\/jbmr.5650020617","volume":"2","author":"AM Parfitt","year":"1987","unstructured":"Parfitt, A. M. et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J. Bone Miner. Res. 2, 595\u2013610 (1987).","journal-title":"J. Bone Miner. Res."},{"key":"BFsrep45189_CR61","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1177\/0363546511430376","volume":"40","author":"P Orth","year":"2012","unstructured":"Orth, P. et al. Effect of subchondral drilling on the microarchitecture of subchondral bone: analysis in a large animal model at 6 months. Am. J. Sports Med. 40, 828\u2013836 (2012).","journal-title":"Am. J. Sports Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep45189.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep45189","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/srep45189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/srep45189.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T23:51:55Z","timestamp":1671839515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep45189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,27]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,5,30]]}},"alternative-id":["BFsrep45189"],"URL":"https:\/\/doi.org\/10.1038\/srep45189","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,27]]},"assertion":[{"value":"16 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"45189"}}