{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:25:37Z","timestamp":1789536337373,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T00:00:00Z","timestamp":1710892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Arthrosehilfe e.V.","award":["EXC2151\u2014390873048"],"award-info":[{"award-number":["EXC2151\u2014390873048"]}]},{"name":"BONFOR-Forschungskommission der Medizinischen Fakult\u00e4t Bonn","award":["EXC2151\u2014390873048"],"award-info":[{"award-number":["EXC2151\u2014390873048"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany\u2019s Excellence Strategy","award":["EXC2151\u2014390873048"],"award-info":[{"award-number":["EXC2151\u2014390873048"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The current gold standard to treat large cartilage defects is autologous chondrocyte transplantation (ACT). As a new surgical method of cartilage regeneration, minced cartilage implantation (MCI) is increasingly coming into focus. The aim of this study is to investigate the influence of chondrogenesis between isolated and cultured chondrocytes compared to cartilage chips in a standardized inflammation model with the proinflammatory cytokine TNF\u03b1. Articular chondrocytes from bovine cartilage were cultured according to the ACT method to passage 3 and transferred to spheroid culture. At the same time, cartilage was fragmented (&lt;1 mm3) to produce cartilage chips. TNF\u03b1 (20 ng\/mL) was supplemented to simulate an inflammatory process. TNF\u03b1 had a stronger influence on the passaged chondrocytes compared to the non-passaged ones, affecting gene expression profiles differently between isolated chondrocytes and cartilage chips. MCI showed less susceptibility to TNF\u03b1, with reduced IL-6 release and less impact on inflammation markers. Biochemical and histological analyses supported these findings, showing a greater negative influence of TNF\u03b1 on the passaged pellet cultures compared to the unpassaged cells and MCI constructs. This study demonstrated the negative influence of TNF\u03b1 on chondrogenesis in a chondrocyte spheroid culture and cartilage fragment model. Passaged chondrocytes are more sensitive to cytokine influences compared to non-passaged cells and chondrons. This suggests that MCI may have superior regeneration potential in osteoarthritic conditions compared to ACT. Further investigations are necessary for the translation of these findings into clinical practice.<\/jats:p>","DOI":"10.3390\/cells13060546","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T05:56:07Z","timestamp":1710914167000},"page":"546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Comparison of Minced Cartilage Implantation with Autologous Chondrocyte Transplantation in an In Vitro Inflammation Model"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6636-8065","authenticated-orcid":false,"given":"Robert","family":"Ossendorff","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Grede","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7852-2277","authenticated-orcid":false,"given":"Sebastian","family":"Scheidt","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7777-3253","authenticated-orcid":false,"given":"Andreas C.","family":"Strauss","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter C.","family":"Wirtz","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian M.","family":"Salzmann","sequence":"additional","affiliation":[{"name":"Gelenkzentrum Rhein-Main, 65239 Hochheim, Germany"},{"name":"Schulthess Clinic, 8008 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0797-1945","authenticated-orcid":false,"given":"Frank A.","family":"Schildberg","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1249\/MSS.0b013e3181d9eea0","article-title":"Prevalence of chondral defects in athletes\u2019 knees: A systematic review","volume":"42","author":"Flanigan","year":"2010","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.clim.2012.12.011","article-title":"Immunopathogenesis of osteoarthritis","volume":"146","author":"Haseeb","year":"2013","journal-title":"Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"629","DOI":"10.2106\/JBJS.20.01161","article-title":"Chondral Lesions of the Knee: An Evidence-Based Approach","volume":"103","author":"Dekker","year":"2021","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.knee.2016.02.001","article-title":"Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group \u201cClinical Tissue Regeneration\u201d of the German Society of Orthopaedics and Trauma (DGOU)","volume":"23","author":"Niemeyer","year":"2016","journal-title":"Knee"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1007\/s00167-019-05786-8","article-title":"Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroid technology is independent of spheroid dose after 4 years","volume":"28","author":"Niemeyer","year":"2020","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1177\/1947603516630786","article-title":"Long-Term Outcomes after Autologous Chondrocyte Implantation: A Systematic Review at Mean Follow-Up of 11.4 Years","volume":"7","author":"Pareek","year":"2016","journal-title":"Cartilage"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1007\/s00167-016-4300-1","article-title":"Comparative efficacy of cartilage repair procedures in the knee: A network meta-analysis","volume":"25","author":"Riboh","year":"2017","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1177\/0363546520928337","article-title":"Prospective Long-term Follow-up of Autologous Chondrocyte Implantation With Periosteum Versus Matrix-Associated Autologous Chondrocyte Implantation: A Randomized Clinical Trial","volume":"48","author":"Kruck","year":"2020","journal-title":"Am. J. Sports Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1124S","DOI":"10.1177\/1947603520942952","article-title":"Autologous Minced Cartilage Implantation for Treatment of Chondral and Osteochondral Lesions in the Knee Joint: An Overview","volume":"13","author":"Salzmann","year":"2020","journal-title":"Cartilage"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.joca.2014.08.005","article-title":"Enhanced cell-induced articular cartilage regeneration by chondrons; the influence of joint damage and harvest site","volume":"22","author":"Vonk","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/jcb.22533","article-title":"Preservation of the chondrocyte\u2019s pericellular matrix improves cell-induced cartilage formation","volume":"110","author":"Vonk","year":"2010","journal-title":"J. Cell Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Frodl, A., Siegel, M., Fuchs, A., Wagner, F.C., Schmal, H., Izadpanah, K., and Yilmaz, T. (2022). Minced Cartilage Is a One-Step Cartilage Repair Procedure for Small Defects in the Knee-A Systematic-Review and Meta-Analysis. J. Pers. Med., 12.","DOI":"10.3390\/jpm12111923"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2325967119853773","DOI":"10.1177\/2325967119853773","article-title":"One-Step Autologous Minced Cartilage Procedure for the Treatment of Knee Joint Chondral and Osteochondral Lesions: A Series of 27 Patients With 2-Year Follow-up","volume":"7","author":"Massen","year":"2019","journal-title":"Orthop. J. Sports Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/19476035221126343","article-title":"Minced Autologous Chondral Fragments with Fibrin Glue as a Simple Promising One-Step Cartilage Repair Procedure: A Clinical and MRI Study at 12-Month Follow-Up","volume":"13","author":"Wodzig","year":"2022","journal-title":"Cartilage"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s00402-016-2453-5","article-title":"Cartilage repair surgery for full-thickness defects of the knee in Germany: Indications and epidemiological data from the German Cartilage Registry (KnorpelRegister DGOU)","volume":"136","author":"Niemeyer","year":"2016","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/S0020-1383(15)30012-7","article-title":"Defect type, localization and marker gene expression determines early adverse events of matrix-associated autologous chondrocyte implantation","volume":"46","author":"Angele","year":"2015","journal-title":"Injury"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/1756-185X.12431","article-title":"Pro-inflammatory IL-1beta and\/or TNF-alpha up-regulate matrix metalloproteases-1 and -3 mRNA in chondrocyte subpopulations potentially pathogenic in osteoarthritis: In situ hybridization studies on a single cell level","volume":"19","author":"Kunisch","year":"2016","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/abbs\/gmu116","article-title":"Interleukin-1\u03b2 and tumor necrosis factor-\u03b1 increase stiffness and impair contractile function of articular chondrocytes","volume":"47","author":"Chen","year":"2015","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e127","DOI":"10.1016\/j.eats.2016.09.011","article-title":"Second-Generation Autologous Minced Cartilage Repair Technique","volume":"6","author":"Salzmann","year":"2017","journal-title":"Arthrosc. Tech."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1177\/0363546517737497","article-title":"Autologous Chondrocyte Implantation in Osteoarthritic Surroundings: TNF\u03b1 and Its Inhibition by Adalimumab in a Knee-Specific Bioreactor","volume":"46","author":"Ossendorff","year":"2018","journal-title":"Am. J. Sports Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/0003-2697(80)90165-7","article-title":"A simple, rapid, and sensitive DNA assay procedure","volume":"102","author":"Labarca","year":"1980","journal-title":"Anal. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3109\/03008208209160269","article-title":"A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures","volume":"9","author":"Farndale","year":"1982","journal-title":"Connect. Tissue Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1089\/ten.2006.12.3171","article-title":"Effects of simple and complex motion patterns on gene expression of chondrocytes seeded in 3D scaffolds","volume":"12","author":"Grad","year":"2006","journal-title":"Tissue Eng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1104","DOI":"10.1002\/jsp2.1104","article-title":"Proinflammatory intervertebral disc cell and organ culture models induced by tumor necrosis factor alpha","volume":"3","author":"Du","year":"2020","journal-title":"JOR Spine"},{"key":"ref_25","first-page":"57","article-title":"Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelsch\u00e4den am Kniegelenk","volume":"161","author":"Niemeyer","year":"2022","journal-title":"Z. Orthop. Unfall"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/322547a0","article-title":"Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage","volume":"322","author":"Saklatvala","year":"1986","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1002\/art.1780400604","article-title":"In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy","volume":"40","author":"Pelletier","year":"1997","journal-title":"Arthritis Rheum."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/art.23302","article-title":"Secretion of matrix metalloproteinase 3 by expanded articular chondrocytes as a predictor of ectopic cartilage formation capacity in vivo","volume":"58","author":"Pelttari","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1195S","DOI":"10.1177\/1947603520968884","article-title":"Scientific Developments and Clinical Applications Utilizing Chondrons and Chondrocytes with Matrix for Cartilage Repair","volume":"13","author":"Shah","year":"2020","journal-title":"Cartilage"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1053\/joca.2002.0517","article-title":"The influence of the pericellular microenvironment on the chondrocyte response to osmotic challenge","volume":"10","author":"Hing","year":"2002","journal-title":"Osteoarthr. Cartil."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/BF00436773","article-title":"Closure of osteochondral lesions using chondral fragments and fibrin adhesive","volume":"101","author":"Albrecht","year":"1983","journal-title":"Arch. Orthop. Trauma. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2325967119867618","DOI":"10.1177\/2325967119867618","article-title":"Chondrocytes From Device-Minced Articular Cartilage Show Potent Outgrowth Into Fibrin and Collagen Hydrogels","volume":"7","author":"Levinson","year":"2019","journal-title":"Orthop. J. Sports Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1177\/03635465221101004","article-title":"Effect of Mechanical Mincing on Minimally Manipulated Articular Cartilage for Surgical Transplantation","volume":"50","author":"Evuarherhe","year":"2022","journal-title":"Am. J. Sports Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1016\/j.arthro.2015.06.025","article-title":"The Degree of Chondral Fragmentation Affects Extracellular Matrix Production in Cartilage Autograft Implantation: An In Vitro Study","volume":"31","author":"Bonasia","year":"2015","journal-title":"Arthroscopy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e97","DOI":"10.1016\/j.eats.2020.09.015","article-title":"Arthroscopic Minced Cartilage Implantation (MCI): A Technical Note","volume":"10","author":"Schneider","year":"2021","journal-title":"Arthrosc. Tech."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.orthres.2004.08.008","article-title":"Rapid phenotypic changes in passaged articular chondrocyte subpopulations","volume":"23","author":"Darling","year":"2005","journal-title":"J. Orthop. Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/6\/546\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:16:26Z","timestamp":1760105786000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/6\/546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,20]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["cells13060546"],"URL":"https:\/\/doi.org\/10.3390\/cells13060546","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,20]]}}}