{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:55:55Z","timestamp":1792173355388,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mutual State Education Development Funds of Lithuania-Latvia-Taiwan: Research Council of Lithuania (LMTLT)","award":["S-LLT-18-4"],"award-info":[{"award-number":["S-LLT-18-4"]}]},{"name":"Mutual State Education Development Funds of Lithuania-Latvia-Taiwan: Research Council of Lithuania (LMTLT)","award":["LV-LT-TW\/2020\/1"],"award-info":[{"award-number":["LV-LT-TW\/2020\/1"]}]},{"name":"Agency Republic of Latvia (SEDA)","award":["S-LLT-18-4"],"award-info":[{"award-number":["S-LLT-18-4"]}]},{"name":"Agency Republic of Latvia (SEDA)","award":["LV-LT-TW\/2020\/1"],"award-info":[{"award-number":["LV-LT-TW\/2020\/1"]}]},{"name":"Taipei Mission in Lithuania and Latvia","award":["S-LLT-18-4"],"award-info":[{"award-number":["S-LLT-18-4"]}]},{"name":"Taipei Mission in Lithuania and Latvia","award":["LV-LT-TW\/2020\/1"],"award-info":[{"award-number":["LV-LT-TW\/2020\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr\/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr\/Gel\/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr\/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr\/Gel\/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr\/Gel\/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo.<\/jats:p>","DOI":"10.3390\/ijms24043451","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T02:32:07Z","timestamp":1675909927000},"page":"3451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5484-9163","authenticated-orcid":false,"given":"Ilona","family":"Uzieliene","sequence":"first","affiliation":[{"name":"Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiva","family":"Bironaite","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolita","family":"Pachaleva","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edvardas","family":"Bagdonas","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5517-1240","authenticated-orcid":false,"given":"Arkadij","family":"Sobolev","sequence":"additional","affiliation":[{"name":"Latvian Institute of Organic Synthesis, LV-1006 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2316-5751","authenticated-orcid":false,"given":"Wei-Bor","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, National Taiwan University, Taipei 104, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giedrius","family":"Kvedaras","sequence":"additional","affiliation":[{"name":"Clinic of Rheumatology, Orthopaedics Traumatology and Reconstructive Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiva","family":"Bernotiene","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.matbio.2018.05.005","article-title":"Cartilage Diseases","volume":"71\u201372","author":"Krishnan","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/rb\/rbz022","article-title":"Advances of Injectable Hydrogel-Based Scaffolds for Cartilage Regeneration","volume":"6","author":"Li","year":"2019","journal-title":"Regen. Biomater."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s10237-006-0039-9","article-title":"A Theoretical Analysis of Water Transport Through Chondrocytes","volume":"6","author":"Ateshian","year":"2007","journal-title":"Biomech. Model Mechanobiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrrheum.2014.157","article-title":"Repair and Tissue Engineering Techniques for Articular Cartilage","volume":"11","author":"Makris","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1016\/j.biopha.2018.11.099","article-title":"Mesenchymal Stem Cell-Based Therapy of Osteoarthritis: Current Knowledge and Future Perspectives","volume":"109","author":"Harrell","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13287-021-02689-9","article-title":"Mesenchymal Stromal Cell-Based Therapy for Cartilage Regeneration in Knee Osteoarthritis","volume":"13","author":"Xiang","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1007\/s00167-020-05859-z","article-title":"Intraarticular Injection of Bone Marrow-Derived Mesenchymal Stem Cells Enhances Regeneration in Knee Osteoarthritis","volume":"28","author":"Doyle","year":"2020","journal-title":"Knee Surg. Sport. Traumatol. Arthrosc."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Uzieliene, I., Bironaite, D., Bernotas, P., Sobolev, A., and Bernotiene, E. (2021). Mechanotransducive Biomimetic Systems for Chondrogenic Differentiation In Vitro. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189690"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s40204-014-0031-x","article-title":"Injectable Scaffold as Minimally Invasive Technique for Cartilage Tissue Engineering: In Vitro and in Vivo Preliminary Study","volume":"3","author":"Solouk","year":"2014","journal-title":"Prog. Biomater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1089\/ten.teb.2018.0245","article-title":"Hybrid and Composite Scaffolds Based on Extracellular Matrices for Cartilage Tissue Engineering","volume":"25","author":"Setayeshmehr","year":"2019","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.matbio.2007.07.002","article-title":"Chondroitin Sulfate Based Niches for Chondrogenic Differentiation of Mesenchymal Stem Cells","volume":"27","author":"Varghese","year":"2008","journal-title":"Matrix Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20014","DOI":"10.1038\/srep20014","article-title":"An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan\/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2100435","DOI":"10.1002\/mabi.202100435","article-title":"Chondroitin and Dermatan Sulfate Bioinks for 3D Bioprinting and Cartilage Regeneration","volume":"22","author":"Zabala","year":"2022","journal-title":"Macromol. Biosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.msec.2018.12.014","article-title":"Injectable Hydrogels from Enzyme-Catalyzed Crosslinking as BMSCs-Laden Scaffold for Bone Repair and Regeneration","volume":"96","author":"Zhang","year":"2019","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"954501","DOI":"10.3389\/fbioe.2022.954501","article-title":"Advanced Injectable Hydrogels for Cartilage Tissue Engineering","volume":"10","author":"Zhu","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1039\/D1LC01069G","article-title":"Emulating the Chondrocyte Microenvironment Using Multi-Directional Mechanical Stimulation in a Cartilage-on-Chip","volume":"22","author":"Hendriks","year":"2022","journal-title":"Lab Chip"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Verbruggen, S.W. (2018). Mechanobiology in Health and Disease, Academic Press.","DOI":"10.1016\/B978-0-12-812952-4.00006-4"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lee, H.-S., Salter, D.M., Lee, H.-S., and Salter, D.M. (2015). Biomechanics of Cartilage and Osteoarthritis, IntechOpen.","DOI":"10.5772\/60011"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Uzieliene, I., Bernotas, P., Mobasheri, A., and Bernotiene, E. (2018). The Role of Physical Stimuli on Calcium Channels in Chondrogenic Differentiation of Mesenchymal Stem Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19102998"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1089\/ten.teb.2018.0006","article-title":"A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties","volume":"24","author":"Salinas","year":"2018","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rim, Y.A., Nam, Y., and Ju, J.H. (2020). The Role of Chondrocyte Hypertrophy and Senescence in Osteoarthritis Initiation and Progression. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072358"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.actbio.2020.10.025","article-title":"Complex Mechanical Behavior of Human Articular Cartilage and Hydrogels for Cartilage Repair","volume":"118","author":"Weizel","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1089\/ten.teb.2014.0661","article-title":"Regeneration of Articular Cartilage Surface: Morphogens, Cells, and Extracellular Matrix Scaffolds","volume":"21","author":"Sakata","year":"2015","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1021\/acsnano.0c08253","article-title":"Magnetic Nanocomposite Hydrogels for Tissue Engineering: Design Concepts and Remote Actuation Strategies to Control Cell Fate","volume":"15","author":"Pardo","year":"2021","journal-title":"ACS Nano"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.csm.2017.02.001","article-title":"Basic Science of Articular Cartilage","volume":"36","author":"Carballo","year":"2017","journal-title":"Clin. Sports Med."},{"key":"ref_26","unstructured":"Chen, Y. (2022). Musculoskeletal Tissue Engineering, Elsevier."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/jor.23670","article-title":"Mechanical Stimulation of Mesenchymal Stem Cells: Implications for Cartilage Tissue Engineering","volume":"36","author":"Fahy","year":"2018","journal-title":"J. Orthop. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"120555","DOI":"10.1016\/j.biomaterials.2020.120555","article-title":"The Regulation of Cartilage Extracellular Matrix Homeostasis in Joint Cartilage Degeneration and Regeneration","volume":"268","author":"Peng","year":"2021","journal-title":"Biomaterials"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.rehab.2016.03.004","article-title":"Osteoarthritis Biomarkers Derived from Cartilage Extracellular Matrix: Current Status and Future Perspectives","volume":"59","author":"Henrotin","year":"2016","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.4137\/BMI.S645","article-title":"Cartilage Oligomeric Matrix Protein (COMP): A Biomarker of Arthritis","volume":"4","author":"Tseng","year":"2009","journal-title":"Biomark. Insights"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.matbio.2018.02.023","article-title":"Cartilage Oligomeric Matrix Protein: COMPopathies and Beyond","volume":"71\u201372","author":"Posey","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1002\/jcb.23455","article-title":"Cartilage Oligomeric Matrix Protein Enhances Matrix Assembly during Chondrogenesis of Human Mesenchymal Stem Cells","volume":"113","author":"Calderon","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1186\/ar2278","article-title":"Glycosaminoglycan Profiles of Repair Tissue Formed Following Autologous Chondrocyte Implantation Differ from Control Cartilage","volume":"9","author":"Sharma","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1021\/acs.molpharmaceut.0c01254","article-title":"Real-Time Quantification of Cartilage Degeneration by GAG-Targeted Cationic Nanoparticles for Efficient Therapeutic Monitoring in Living Mice","volume":"18","author":"Xiao","year":"2021","journal-title":"Mol. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.bioactmat.2020.09.030","article-title":"Advanced Hydrogels for the Repair of Cartilage Defects and Regeneration","volume":"6","author":"Wei","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"eaaf3627","DOI":"10.1126\/science.aaf3627","article-title":"Advances in Engineering Hydrogels","volume":"356","author":"Zhang","year":"2017","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/jor.24238","article-title":"Effect of Interface Mechanical Discontinuities on Scaffold-Cartilage Integration","volume":"37","author":"Yodmuang","year":"2019","journal-title":"J. Orthop. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ye, B., Wu, B., Su, Y., Sun, T., and Guo, X. (2022). Recent Advances in the Application of Natural and Synthetic Polymer-Based Scaffolds in Musculoskeletal Regeneration. Polymers, 14.","DOI":"10.3390\/polym14214566"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rojas-Murillo, J.A., Simental-Mend\u00eda, M.A., Moncada-Saucedo, N.K., Delgado-Gonzalez, P., Islas, J.F., Roacho-P\u00e9rez, J.A., and Garza-Trevi\u00f1o, E.N. (2022). Physical, Mechanical, and Biological Properties of Fibrin Scaffolds for Cartilage Repair. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179879"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17014","DOI":"10.1038\/boneres.2017.14","article-title":"Injectable Hydrogels for Cartilage and Bone Tissue Engineering","volume":"5","author":"Liu","year":"2017","journal-title":"Bone Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6351","DOI":"10.1021\/acs.cgd.9b00831","article-title":"Mineralization of Layer-by-Layer Ultrathin Films Containing Microfluidic-Produced Hydroxyapatite Nanorods","volume":"19","author":"Rial","year":"2019","journal-title":"Cryst. Growth Des."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5025","DOI":"10.1039\/D1TB00717C","article-title":"Engineering Next-Generation Bioinks with Nanoparticles: Moving from Reinforcement Fillers to Multifunctional Nanoelements","volume":"9","author":"Bakht","year":"2021","journal-title":"J. Mater. Chem. B"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1038\/s41467-022-32792-1","article-title":"Magnetically assisted drop-on-demand 3D printing of microstructured multimaterial composites","volume":"13","author":"Liu","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1039\/D1BM00482D","article-title":"A Chondroitin Sulfate Based Injectable Hydrogel for Delivery of Stem Cells in Cartilage Regeneration","volume":"9","author":"Li","year":"2021","journal-title":"Biomater. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"118330","DOI":"10.1016\/j.carbpol.2021.118330","article-title":"Gradient Chondroitin Sulfate\/Poly (\u03b3-Glutamic Acid) Hydrogels Inducing Differentiation of Stem Cells for Cartilage Tissue Engineering","volume":"270","author":"Liu","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.ijbiomac.2020.02.002","article-title":"An Injectable Carboxymethyl Chitosan-Methylcellulose-Pluronic Hydrogel for the Encapsulation of Meloxicam Loaded Nanoparticles","volume":"151","author":"Fattahpour","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1177\/1947603519841682","article-title":"Injectable Scaffold for Bone Marrow Stem Cells and Bone Morphogenetic Protein-2 to Repair Cartilage","volume":"12","author":"Vayas","year":"2021","journal-title":"Cartilage"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Couce, J., Tom\u00e1s, M., Fuentes, G., Que, I., Almirall, A., and Cruz, L.J. (2022). Chitosan\/Pluronic F127 Thermosensitive Hydrogel as an Injectable Dexamethasone Delivery Carrier. Gels, 8.","DOI":"10.3390\/gels8010044"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Dolzani, P., Assirelli, E., Pulsatelli, L., Meliconi, R., Mariani, E., and Neri, S. (2019). Ex Vivo Physiological Compression of Human Osteoarthritis Cartilage Modulates Cellular and Matrix Components. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222947"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1002\/term.2653","article-title":"Biomimetic Scaffolds and Dynamic Compression Enhance the Properties of Chondrocyte- and MSC-Based Tissue-Engineered Cartilage","volume":"12","author":"Sawatjui","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/rb\/rbz005","article-title":"Dynamic Mechanical Loading Facilitated Chondrogenic Differentiation of Rabbit BMSCs in Collagen Scaffolds","volume":"6","author":"Cao","year":"2019","journal-title":"Regen. Biomater."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"697281","DOI":"10.3389\/fbioe.2021.697281","article-title":"Effects of Mechanical Compression on Chondrogenesis of Human Synovium-Derived Mesenchymal Stem Cells in Agarose Hydrogel","volume":"9","author":"Ge","year":"2021","journal-title":"Front. Bioeng. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:27:49Z","timestamp":1760120869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,9]]},"references-count":52,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043451"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043451","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,9]]}}}