{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:34:09Z","timestamp":1785418449403,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008367","name":"Universit\u00e9 Libre de Bruxelles","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008367","id-type":"DOI","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/01r9htc13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Articular cartilage repair remains a clinical challenge due to the tissue\u2019s limited regenerative capacity. This study aimed to perform in vivo tracking of human chondrocytes after implantation in femoral trochlear defects. Moreover, we tested the rabbit xenogeneic model to assess the efficacy of human chondrocyte implantation, either in the form of cell suspension or in the form of spheroids, for cartilage regeneration. Chondrocytes were isolated from osteoarthritic human knees, expanded in vitro, and labeled with gold nanoparticles (AuNPs) to enable their in vivo tracking. AuNP labeling did not impair chondrocyte viability and spheroid formation. Knee osteochondral defects were then treated with the labeled cells, either injected intra-articularly as single cells in suspension or aggregated into scaffold-free spheroids and further implanted. Two weeks post-transplantation, macroscopic and histological evaluations were performed to assess cartilage repair and cell engraftment. The presence of labeled cells was detected only in spheroid-treated lesions that exhibited significantly greater tissue filling as reflected by O\u2019Driscoll and ICRS scores. Moreover, localized expression of type II collagen was observed in some of the spheroid-treated defects. In contrast, single cell intra-articular injection resulted in poor cartilage repair and the absence of labeled cells at the defect site. Altogether, our results indicate that human chondrocyte delivery in the form of scaffold-free spheroids in rabbit knees enhances their retention at the defect site and supports early stages of cartilage regeneration. Moreover, our results suggest that the xenogeneic rabbit model could be a useful platform for evaluating human-derived cell therapies.<\/jats:p>","DOI":"10.3390\/ijms27146381","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:32:54Z","timestamp":1784539974000},"page":"6381","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Cartilage Repair After Implantation of Labeled Human Chondrocytes as Free Cells or Spheroids in Rabbit Knees"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9402-6401","authenticated-orcid":false,"given":"Jacques","family":"Hernigou","sequence":"first","affiliation":[{"name":"Laboratory of Bone and Metabolic Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Orthopedics and Traumatology Department, EpiCURA Hospital, 7331 Baudour, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Vertongen","sequence":"additional","affiliation":[{"name":"Laboratory of Bone and Metabolic Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4513-2389","authenticated-orcid":false,"given":"Esfandiar","family":"Chahidi","sequence":"additional","affiliation":[{"name":"Orthopedics and Traumatology Department, CHU (Centres Hospitaliers Universitaires) Helora\u2014La Louvi\u00e8re Hospital, 7100 La Louvi\u00e8re, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gaspard","sequence":"additional","affiliation":[{"name":"D\u00e9partement D\u2019Enseignement de la Biologie, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lechanteur","sequence":"additional","affiliation":[{"name":"Laboratory of Bone and Metabolic Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaelle","family":"Lapouge","sequence":"additional","affiliation":[{"name":"Erasme Animal Facility, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9388-7995","authenticated-orcid":false,"given":"Joanne","family":"Rasschaert","sequence":"additional","affiliation":[{"name":"Laboratory of Bone and Metabolic Biochemistry, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/1941738109350438","article-title":"The Basic Science of Articular Cartilage: Structure, Composition, and Function","volume":"1","author":"Bedi","year":"2009","journal-title":"Sports Health A Multidiscip. Approach"},{"key":"ref_2","first-page":"91","article-title":"Current and Emerging Techniques in Articular Cartilage Repair","volume":"82","author":"Ross","year":"2024","journal-title":"Bull. Hosp. Jt. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Lin, H., and Tuan, R.S. (2017). Overview: State of the Art and Future Prospectives for Cartilage Repair. Cartilage, Springer.","DOI":"10.1007\/978-3-319-53316-2_1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1177\/03635465211003595","article-title":"Marrow Stimulation Has Relatively Inferior Patient-Reported Outcomes in Cartilage Restoration Surgery of the Knee: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"50","author":"Abraamyan","year":"2022","journal-title":"Am. J. Sports Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1177\/0363546515609597","article-title":"Bone Marrow Concentrate Improves Early Cartilage Phase Maturation of a Scaffold Plug in the Knee: A Comparative Magnetic Resonance Imaging Analysis to Platelet-Rich Plasma and Control","volume":"44","author":"Krych","year":"2016","journal-title":"Am. J. Sports Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"994","DOI":"10.2106\/JBJS.I.00895","article-title":"Management of Articular Cartilage Defects of the Knee","volume":"92","author":"Bedi","year":"2010","journal-title":"J. Bone Jt. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1177\/1947603517736108","article-title":"Reserve or Resident Progenitors in Cartilage? Comparative Analysis of Chondrocytes versus Chondroprogenitors and Their Role in Cartilage Repair","volume":"9","author":"Vinod","year":"2018","journal-title":"Cartilage"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s10439-019-02348-4","article-title":"Scaffold Free Microtissue Formation for Enhanced Cartilage Repair","volume":"48","author":"Beyls","year":"2020","journal-title":"Ann. Biomed. Eng."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Vonk, L.A., Ro\u00ebl, G., Hernigou, J., Kaps, C., and Hernigou, P. (2021). Role of Matrix-Associated Autologous Chondrocyte Implantation with Spheroids in the Treatment of Large Chondral Defects in the Knee: A Systematic Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137149"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1359\/jbmr.2002.17.8.1420","article-title":"In Vitro Engineering of Human Autogenous Cartilage","volume":"17","author":"Anderer","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_11","first-page":"455","article-title":"Long-Term Effects of Chondrospheres on Cartilage Lesions in an Autologous Chondrocyte Implantation Model as Investigated in the SCID Mouse Model","volume":"23","author":"Schubert","year":"2009","journal-title":"Int. J. Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s12026-015-8720-7","article-title":"Immunology and Cartilage Regeneration","volume":"63","author":"Smith","year":"2015","journal-title":"Immunol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.dci.2018.10.003","article-title":"Rabbit Models of Human Diseases for Diagnostics and Therapeutics Development","volume":"92","author":"Mage","year":"2019","journal-title":"Dev. Comp. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Soares, J., Pinheiro, A., and Esteves, P.J. (2022). The Rabbit as an Animal Model to Study Innate Immunity Genes: Is It Better than Mice?. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.981815"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1067-1927.2004.012309.x","article-title":"Xeno-Implantation of Pig Chondrocytes into Rabbit to Treat Localized Articular Cartilage Defects: An Animal Model","volume":"12","author":"Ramallal","year":"2004","journal-title":"Wound Repair Regen."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/smll.201100001","article-title":"Cellular Uptake, Intracellular Trafficking, and Cytotoxicity of Nanomaterials","volume":"7","author":"Zhao","year":"2011","journal-title":"Small"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gr\u00e4ssel, S., and Asz\u00f3di, A. (2017). Cartilage, Springer International Publishing.","DOI":"10.1007\/978-3-319-53316-2"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1007\/s00264-018-3999-3","article-title":"Effects of Press-Fit Biphasic (Collagen and HA\/\u03b2TCP) Scaffold with Cell-Based Therapy on Cartilage and Subchondral Bone Repair Knee Defect in Rabbits","volume":"42","author":"Hernigou","year":"2018","journal-title":"Int. Orthop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"579","DOI":"10.2106\/00004623-199404000-00013","article-title":"Mesenchymal Cell-Based Repair of Large, Full-Thickness Defects of Articular Cartilage","volume":"76","author":"Wakitani","year":"1994","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3109\/17453679609002337","article-title":"Immunosuppressive Effect of Tacrolimus (FK-506). Bone Xenografts in Rabbits","volume":"67","author":"Ikebe","year":"1996","journal-title":"Acta Orthop. Scand."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1007\/s00167-013-2426-y","article-title":"Xenotransplantation of Human Mesenchymal Stem Cells for Repair of Osteochondral Defects in Rabbits Using Osteochondral Biphasic Composite Constructs","volume":"22","author":"Jang","year":"2014","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/jor.21096","article-title":"Failure of Xenoimplantation Using Porcine Synovium-Derived Stem Cell-Based Cartilage Tissue Constructs for the Repair of Rabbit Osteochondral Defects","volume":"28","author":"Pei","year":"2010","journal-title":"J. Orthop. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.joca.2012.06.016","article-title":"Redifferentiation of Dedifferentiated Human Articular Chondrocytes: Comparison of 2D and 3D Cultures","volume":"20","author":"Caron","year":"2012","journal-title":"Osteoarthr. Cartil."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1073\/pnas.1911734116","article-title":"Unexpected Intracellular Biodegradation and Recrystallization of Gold Nanoparticles","volume":"117","author":"Balfourier","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"225","DOI":"10.22203\/eCM.v035a16","article-title":"Comprehensive High-Resolution Genomic Profiling and Cytogenetics of Human Chondrocyte Cultures by GTG-Banding, Locus-Specific FISH, SKY and SNP Array","volume":"35","author":"Wallenborn","year":"2018","journal-title":"Eur. Cells Mater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8319","DOI":"10.1038\/s41598-025-92071-z","article-title":"Autologous Serum Supplementation Promotes the Phenotype Maintenance of Human Chondrocytes with Increased Cellular Autophagy","volume":"15","author":"Yin","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1002\/jor.20523","article-title":"Gene Expression Profiles of Human Chondrocytes During Passaged Monolayer Cultivation","volume":"26","author":"Lin","year":"2008","journal-title":"J. Orthop. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1089\/scd.2007.0049","article-title":"Alpha10 Integrin Expression Is Up-Regulated on Fibroblast Growth Factor-2-Treated Mesenchymal Stem Cells with Improved Chondrogenic Differentiation Potential","volume":"16","author":"Varas","year":"2007","journal-title":"Stem Cells Dev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1242\/jcs.01678","article-title":"Loss of Alpha10beta1 Integrin Expression Leads to Moderate Dysfunction of Growth Plate Chondrocytes","volume":"118","author":"Bengtsson","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/978-94-017-9153-3_4","article-title":"Integrin A10\u03b21: A Collagen Receptor Critical in Skeletal Development","volume":"819","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.bbrc.2006.04.123","article-title":"Regulation of Integrin Alpha10 Expression in Chondrocytes by the Transcription Factors AP-2epsilon and Ets-1","volume":"345","author":"Wenke","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"129S","DOI":"10.1177\/19476035211059600","article-title":"Progenitor Cells in Healthy and Osteoarthritic Human Cartilage Have Extensive Culture Expansion Capacity While Retaining Chondrogenic Properties","volume":"13","author":"Rikkers","year":"2021","journal-title":"Cartilage"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41536-021-00203-6","article-title":"The Clinical Potential of Articular Cartilage-Derived Progenitor Cells: A Systematic Review","volume":"7","author":"Rikkers","year":"2022","journal-title":"npj Regen. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pettenuzzo, S., Arduino, A., Belluzzi, E., Pozzuoli, A., Fontanella, C.G., Ruggieri, P., Salomoni, V., Majorana, C., and Berardo, A. (2023). Biomechanics of Chondrocytes and Chondrons in Healthy Conditions and Osteoarthritis: A Review of the Mechanical Characterisations at the Microscale. Biomedicines, 11.","DOI":"10.3390\/biomedicines11071942"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/smll.200700378","article-title":"Size-Dependent Cytotoxicity of Gold Nanoparticles","volume":"3","author":"Pan","year":"2007","journal-title":"Small"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1002\/jat.2912","article-title":"Effects of Gold and Silver Nanoparticles in Cultured Human Osteoarthritic Chondrocytes","volume":"33","author":"Pascarelli","year":"2013","journal-title":"J. Appl. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1007\/s00167-022-07194-x","article-title":"Sustained Superiority in KOOS Subscores after Matrix-Associated Chondrocyte Implantation Using Spheroids Compared to Microfracture","volume":"31","author":"Hoburg","year":"2023","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"23259671211053380","DOI":"10.1177\/23259671211053380","article-title":"Safety and Efficacy of Matrix-Associated Autologous Chondrocyte Implantation with Spheroids for Patellofemoral or Tibiofemoral Defects: A 5-Year Follow-up of a Phase 2, Dose-Confirmation Trial","volume":"10","author":"Hoburg","year":"2022","journal-title":"Orthop. J. Sports Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1007\/s00167-021-06584-x","article-title":"Good Healing Potential of Patellar Chondral Defects After All-Arthroscopic Autologous Chondrocyte Implantation with Spheroids: A Second-Look Arthroscopic Assessment","volume":"30","author":"Sumida","year":"2022","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s13770-019-00231-w","article-title":"Rapid Cartilage Regeneration of Spheroids Composed of Human Nasal Septum-Derived Chondrocyte in Rat Osteochondral Defect Model","volume":"17","author":"Jeon","year":"2020","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1177\/1947603518798890","article-title":"Extracellular Matrix Determines Biomechanical Properties of Chondrospheres During Their Maturation In Vitro","volume":"11","author":"Omelyanenko","year":"2020","journal-title":"Cartilage"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0014-4827(03)00130-7","article-title":"Redifferentiation of Dedifferentiated Chondrocytes and Chondrogenesis of Human Bone Marrow Stromal Cells via Chondrosphere Formation with Expression Profiling by Large-Scale cDNA Analysis","volume":"288","author":"Imabayashi","year":"2003","journal-title":"Exp. Cell Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1089\/ten.2006.12.1675","article-title":"Effect of Seeding and Bioreactor Culture Conditions on the Development of Human Tissue-Engineered Cartilage","volume":"12","author":"Mahmoudifar","year":"2006","journal-title":"Tissue Eng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1186\/s12967-016-1065-8","article-title":"An Ex Vivo Human Cartilage Repair Model to Evaluate the Potency of a Cartilage Cell Transplant","volume":"14","author":"Bartz","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0092-8674(82)90027-7","article-title":"Dedifferentiated Chondrocytes Reexpress the Differentiated Collagen Phenotype When Cultured in Agarose Gels","volume":"30","author":"Benya","year":"1982","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1002\/jor.20874","article-title":"Paracrine Effect of Transplanted Rib Chondrocyte Spheroids Supports Formation of Secondary Cartilage Repair Tissue","volume":"27","author":"Gelse","year":"2009","journal-title":"J. Orthop. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-3-031-30040-0_5","article-title":"Potency Assay Considerations for Cartilage Repair, Osteoarthritis and Use of Extracellular Vesicles","volume":"1420","author":"Vonk","year":"2023","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Mustonen, A.-M., and Nieminen, P. (2021). Extracellular Vesicles and Their Potential Significance in the Pathogenesis and Treatment of Osteoarthritis. Pharmaceuticals, 14.","DOI":"10.3390\/ph14040315"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wu, K.-C., Yang, H.-I., Chang, Y.-H., Chiang, R.Y.-S., and Ding, D.-C. (2025). Extracellular Vesicles Derived from Human Umbilical Mesenchymal Stem Cells Transfected with miR-7704 Improved Damaged Cartilage and Reduced Matrix Metallopeptidase 13. Cells, 14.","DOI":"10.3390\/cells14020082"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14630","DOI":"10.1038\/s41598-019-51070-7","article-title":"The Interplay Between Chondrocyte Spheroids and Mesenchymal Stem Cells Boosts Cartilage Regeneration Within a 3D Natural-Based Hydrogel","volume":"9","author":"Scalzone","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1177\/1947603510392913","article-title":"Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair: International Cartilage Repair Society Recommendations Based on Current Scientific Evidence and Standards of Clinical Care","volume":"2","author":"Mithoefer","year":"2011","journal-title":"Cartilage"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.2106\/00004623-198668070-00008","article-title":"The Chondrogenic Potential of Free Autogenous Periosteal Grafts for Biological Resurfacing of Major Full-Thickness Defects in Joint Surfaces Under the Influence of Continuous Passive Motion. An Experimental Investigation in the Rabbit","volume":"68","author":"Keeley","year":"1986","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1007\/s11033-011-0853-8","article-title":"The Restoration of Full-Thickness Cartilage Defects with Mesenchymal Stem Cells (MSCs) Loaded and Cross-Linked Bilayer Collagen Scaffolds on Rabbit Model","volume":"39","author":"Qi","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_54","unstructured":"Grayling, M., Mander, A., and Wason, J. (2017). A Two-Stage Fisher Exact Test for Multi-Arm Studies with Binary Outcome Variables. arXiv."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1093\/brain\/aww137","article-title":"Tauopathy Induced by Low Level Expression of a Human Brain-Derived Tau Fragment in Mice Is Rescued by Phenylbutyrate","volume":"139","author":"Bondulich","year":"2016","journal-title":"Brain"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"S113","DOI":"10.1016\/j.joca.2010.05.026","article-title":"Basic Methods in Histopathology of Joint Tissues","volume":"18","author":"Schmitz","year":"2010","journal-title":"Osteoarthr. Cartil."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6381\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:16:28Z","timestamp":1784607388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6381"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":56,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146381"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146381","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}