{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:32:26Z","timestamp":1784302346000,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Fund","award":["IRI 2\u2014KK.01.2.1.02.0173"],"award-info":[{"award-number":["IRI 2\u2014KK.01.2.1.02.0173"]}]},{"name":"International Society for Applied Biological Sciences (ISABS)","award":["IRI 2\u2014KK.01.2.1.02.0173"],"award-info":[{"award-number":["IRI 2\u2014KK.01.2.1.02.0173"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Micro-fragmented adipose tissue (MFAT) is a promising autologous therapy for knee osteoarthritis. To avoid repeated liposuction procedures for its clinical application, MFAT obtained from patients with knee osteoarthritis was stored at \u221280 \u00b0C in a tissue bank. This study describes the preparation, cryopreservation, thawing, and washing, as well as comprehensive analysis of cell populations in fresh and MFAT thawed after two years. Immunophenotyping of both fresh and thawed MFAT showed a significant presence of endothelial progenitors and pericytes in the stromal vascular fraction. Viability before (59.75%) and after freezing (55.73%) showed no significant difference. However, the average cell count per gram of MFAT was significantly reduced in thawed samples (3.00 \u00d7 105) compared to fresh ones (5.64 \u00d7 105), likely due to processing steps. Thawed MFAT samples showed increased CD73 expression on the CD31highCD34high subset of EP and SA-ASC, as well as increased expression of CD105 on EP, the CD31lowCD34low subset of EP, pericytes, and SA-ASC. Microbiological testing confirmed 100% sterility, and double washing efficiently removed DMSO, confirming sample safety. Histological analysis revealed healthy, uniformly shaped adipocytes with intact membranes. This approach allows accurate estimation of cell yield for intra-articular injection, ensuring delivery of the target cell number into the knee. Quality control analysis confirms that cryopreserved MFAT retains high cellular and structural integrity, supporting its safety and suitability for clinical application.<\/jats:p>","DOI":"10.3390\/ijms26146969","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T09:33:53Z","timestamp":1753090433000},"page":"6969","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cryopreservation and Validation of Microfragmented Adipose Tissue for Autologous Use in Knee Osteoarthritis Treatment"],"prefix":"10.3390","volume":"26","author":[{"given":"Marija","family":"Zeku\u0161i\u0107","sequence":"first","affiliation":[{"name":"Department of Transfusion and Regenerative Medicine, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"},{"name":"Faculty of Biotechnology and Drug Development, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8022-4095","authenticated-orcid":false,"given":"Petar","family":"Brlek","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculty of Science, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"St. Catherine Specialty Hospital, 10000 Zagreb, Croatia"},{"name":"School of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucija","family":"Zeni\u0107","sequence":"additional","affiliation":[{"name":"Greyledge Europe Ltd., 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilim","family":"Molnar","sequence":"additional","affiliation":[{"name":"St. Catherine Specialty Hospital, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Ledinski","sequence":"additional","affiliation":[{"name":"Department of Transfusion and Regenerative Medicine, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Buji\u0107 Mihica","sequence":"additional","affiliation":[{"name":"Department of Transfusion and Regenerative Medicine, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"\u0160timac","sequence":"additional","affiliation":[{"name":"Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7370-0997","authenticated-orcid":false,"given":"Beata","family":"Halassy","sequence":"additional","affiliation":[{"name":"Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snje\u017eana","family":"Rami\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cytology \u2018Ljudevit Jurak\u2019, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Pulji\u0107","sequence":"additional","affiliation":[{"name":"Department of Transfusion and Regenerative Medicine, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiha","family":"Vu\u010demilo","sequence":"additional","affiliation":[{"name":"Department of Transfusion and Regenerative Medicine, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1331-5995","authenticated-orcid":false,"given":"Carlo","family":"Tremolada","sequence":"additional","affiliation":[{"name":"Image Regenerative Clinic, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sre\u0107ko","family":"Sabali\u0107","sequence":"additional","affiliation":[{"name":"Department of Traumatology, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia"},{"name":"Medical School, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Karli","sequence":"additional","affiliation":[{"name":"Greyledge Technologies, LLC, Miami, FL 33133, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7966-6670","authenticated-orcid":false,"given":"Dimitrios","family":"Tsoukas","sequence":"additional","affiliation":[{"name":"Orthopaedic Clinic for Advanced Arthroscopic Sports and Regenerative Surgery Mitera Hospital, 15123 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5565-080X","authenticated-orcid":false,"given":"Dragan","family":"Primorac","sequence":"additional","affiliation":[{"name":"St. Catherine Specialty Hospital, 10000 Zagreb, Croatia"},{"name":"School of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Medical School, University of Split, 21000 Split, Croatia"},{"name":"Forensic Science Program, Department of Biochemistry & Molecular Biology, The Pennsylvania State University, State College, PA 16802, USA"},{"name":"The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, West Haven, CT 06516, USA"},{"name":"Sana Kliniken Oberfranken, 96450 Coburg, Germany"},{"name":"Medical School, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Medical School, University of Mostar, 88000 Mostar, Bosnia and Herzegovina"},{"name":"National Forensic Sciences University, Gandhinagar 382007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, H., Felthaus, O., and Prantl, L. (2025). Adipose Tissue-Derived Therapies for Osteoarthritis: Multifaceted Mechanisms and Clinical Prospects. Cells, 14.","DOI":"10.3390\/cells14090669"},{"key":"ref_2","unstructured":"European Committee (Partial Agreement) on Organ Transplantation (2022). Guide to the Quality and Safety of TISSUES AND CELLS for Human Application European Committee (Partial Agreement) on Organ Transplantation (CD-P-TO), The European Directorate for the Quality of Medicines & HealthCare (EDQM)."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1007\/s00266-020-01847-3","article-title":"Long-Term Survival of Fat Transplants: Controlled Demonstrations","volume":"44","author":"Coleman","year":"2020","journal-title":"Aesth Plast. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Santos, M.E., Garcia-Arranz, M., Andreu, E.J., Garc\u00eda-Hern\u00e1ndez, A.M., L\u00f3pez-Parra, M., Villar\u00f3n, E., Sep\u00falveda, P., Fern\u00e1ndez-Avil\u00e9s, F., Garc\u00eda-Olmo, D., and Prosper, F. (2022). Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.918565"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Casado, S., Del Val Toledo Lobo, M., and Pa\u00edno, C.L. (2017). Dynamics of Plasma Membrane Surface Related to the Release of Extracellular Vesicles by Mesenchymal Stem Cells in Culture. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-07265-x"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Screpis, D., Natali, S., Farinelli, L., Piovan, G., Iacono, V., de Girolamo, L., Vigan\u00f2, M., and Zorzi, C. (2022). Autologous Microfragmented Adipose Tissue for the Treatment of Knee Osteoarthritis: Real-World Data at Two Years Follow-Up. J. Clin. Med., 11.","DOI":"10.3390\/jcm11051268"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/sctm.19-0166","article-title":"Intraoperative Strategies for Minimal Manipulation of Autologous Adipose Tissue for Cell- and Tissue-Based Therapies: Concise Review","volume":"8","author":"Trivisonno","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Chu, D.T., Phuong, T.N.T., Tien, N.L.B., Tran, D.K., Van Thanh, V., Quang, T.L., Truong, D.T., Pham, V.H., Ngoc, V.T.N., and Chu-Dinh, T. (2020). An Update on the Progress of Isolation, Culture, Storage, and Clinical Application of Human Bone Marrow Mesenchymal Stem\/Stromal Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030708"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40634-023-00596-x","article-title":"Successful Isolation of Viable Stem Cells from Cryopreserved Microfragmented Human Adipose Tissue from Patients with Knee Osteoarthritis\u2014A Comparative Study of Isolation by Tissue Explant Culture and Enzymatic Digestion","volume":"10","author":"Bagge","year":"2023","journal-title":"J. Exp. Orthop."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Goncharov, E.N., Koval, O.A., Nikolaevich Bezuglov, E., Encarnacion Ramirez, M.d.J., Engelgard, M., Igorevich, E.I., Saporiti, A., Valentinovich Kotenko, K., and Montemurro, N. (2023). Stromal Vascular Fraction Therapy for Knee Osteoarthritis: A Systematic Review. Medicina, 59.","DOI":"10.3390\/medicina59122090"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s10561-016-9607-0","article-title":"Determination of Residual Dimethylsulfoxide in Cryopreserved Cardiovascular Allografts","volume":"18","author":"Blancke","year":"2017","journal-title":"Cell Tissue Bank."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s10561-018-9700-7","article-title":"The Addition of Albumin Improves Schwann Cells Viability in Nerve Cryopreservation","volume":"19","author":"Domenech","year":"2018","journal-title":"Cell Tissue Bank."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1089\/rej.2014.1656","article-title":"Cryoprotectant Toxicity: Facts, Issues, and Questions","volume":"18","author":"Best","year":"2015","journal-title":"Rejuvenation Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Verheijen, M., Lienhard, M., Schrooders, Y., Clayton, O., Nudischer, R., Boerno, S., Timmermann, B., Selevsek, N., Schlapbach, R., and Gmuender, H. (2019). DMSO Induces Drastic Changes in Human Cellular Processes and Epigenetic Landscape in Vitro. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-40660-0"},{"key":"ref_15","unstructured":"(2006). Commission Directive 2006\/86\/EC of 24 October 2006 Implementing Directive 2004\/23\/EC of the European Parliament and of the Council as Regards Traceability Requirements, Notification of Serious Adverse Reactions and Events and Certain Technical Requirements for the Coding, Processing, Preservation, Storage and Distribution of Human Tissues and Cells. Off. J. Eur. Union, 294, 32\u201350."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4968724","DOI":"10.1155\/2016\/4968724","article-title":"Adipose Derived-Mesenchymal Stem Cells Viability and Differentiating Features for Orthopaedic Reparative Applications: Banking of Adipose Tissue","volume":"2016","author":"Roato","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Polancec, D., Zenic, L., Hudetz, D., Boric, I., Jelec, Z., Rod, E., Vrdoljak, T., Skelin, A., Plecko, M., and Turkalj, M. (2019). Immunophenotyping of a Stromal Vascular Fraction from Microfragmented Lipoaspirate Used in Osteoarthritis Cartilage Treatment and Its Lipoaspirate Counterpart. Genes, 10.","DOI":"10.3390\/genes10060474"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zenic, L., Polancec, D., Hudetz, D., Jelec, Z., Rod, E., Vidovic, D., Staresinic, M., Sabalic, S., Vrdoljak, T., and Petrovic, T. (2021). Polychromatic Flow Cytometric Analysis of Stromal Vascular Fraction from Lipoaspirate and Microfragmented Counterparts Reveals Sex-Related Immunophenotype Differences. Genes, 12.","DOI":"10.3390\/genes12121999"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3934\/celltissue.2017.3.224","article-title":"Patient Use of Autologous Cryopreserved Intact Adipose Tissue from Lipoaspirate","volume":"1","author":"Badowski","year":"2017","journal-title":"AIMS Cell Tissue Eng."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Favaretto, F., Compagnin, C., Cogliati, E., Montagner, G., Dell\u2019Antonia, F., Berna, G., Vettor, R., Milan, G., and Trojan, D. (2023). Characterization of Human Subcutaneous Adipose Tissue and Validation of the Banking Procedure for Autologous Transplantation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098190"},{"key":"ref_21","first-page":"249","article-title":"Knee Osteoarthritis Diagnosis, Treatment and Associated Factors of Progression: Part II","volume":"2","author":"Heidari","year":"2011","journal-title":"Casp. J. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal Criteria for Defining Multipotent Mesenchymal Stromal Cells. The International Society for Cellular Therapy Position Statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.jcyt.2019.08.002","article-title":"Mesenchymal Stem versus Stromal Cells: International Society for Cell & Gene Therapy (ISCT\u00ae) Mesenchymal Stromal Cell Committee Position Statement on Nomenclature","volume":"21","author":"Viswanathan","year":"2019","journal-title":"Cytotherapy"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mali\u010dev, E., and Jazbec, K. (2024). An Overview of Mesenchymal Stem Cell Heterogeneity and Concentration. Pharmaceuticals, 17.","DOI":"10.3390\/ph17030350"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Brooks, A.E.S., Iminitoff, M., Williams, E., Damani, T., Jackson-Patel, V., Fan, V., James, J., Dunbar, P.R., Feisst, V., and Sheppard, H.M. (2020). Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Are a Heterogeneous Population That Demonstrate Rapid Culture-Induced Changes. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01695"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.stem.2008.07.003","article-title":"A Perivascular Origin for Mesenchymal Stem Cells in Multiple Human Organs","volume":"3","author":"Crisan","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/cyto.a.21168","article-title":"Pericytes: A Universal Adult Tissue Stem Cell?","volume":"81 A","author":"Zimmerlin","year":"2012","journal-title":"Cytom. Part A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"256","DOI":"10.4252\/wjsc.v6.i3.256","article-title":"Adipose-Derived Mesenchymal Stromal\/Stem Cells: An Update on Their Phenotype in Vivo and in Vitro","volume":"6","author":"Baer","year":"2014","journal-title":"World J. Stem Cells"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/cyto.a.22227","article-title":"Mesenchymal Markers on Human Adipose Stem\/Progenitor Cells","volume":"83 A","author":"Zimmerlin","year":"2013","journal-title":"Cytom. Part A"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.1074\/jbc.M109.074252","article-title":"Adipocyte Apoptosis, a Link between Obesity, Insulin Resistance, and Hepatic Steatosis","volume":"285","author":"Alkhouri","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hutchings, G., Janowicz, K., Moncrieff, L., Dompe, C., Strauss, E., Kocherova, I., Nawrocki, M.J., Kruszyna, \u0141., Wasiatycz, G., and Antosik, P. (2020). The Proliferation and Differentiation of Adipose-Derived Stem Cells in Neovascularization and Angiogenesis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113790"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1111\/j.1537-2995.2010.02803.x","article-title":"Comparison of Cord Blood Thawing Methods on Cell Recovery, Potency, and Infusion","volume":"50","author":"Regan","year":"2010","journal-title":"Transfusion"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2002425","DOI":"10.1002\/advs.202002425","article-title":"Ice Inhibition for Cryopreservation: Materials, Strategies, and Challenges","volume":"8","author":"Chang","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s40778-016-0053-5","article-title":"Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems\u00ae Technology Development","volume":"2","author":"Tremolada","year":"2016","journal-title":"Curr. Stem Cell Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hudetz, D., Bori\u0107, I., Rod, E., Jele\u010d, \u017d., Radi\u0107, A., Vrdoljak, T., Skelin, A., Lauc, G., Trbojevi\u0107-Akma\u010di\u0107, I., and Ple\u010dko, M. (2017). The Effect of Intra-articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis. Genes, 8.","DOI":"10.3390\/genes8100270"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bodiroga-Vukobrat, N., Rukavina, D., Paveli\u0107, K., and Sander, G.G. (2019). The Future of Cartilage Repair. Personalized Medicine in Healthcare Systems: Legal, Medical and Economic Implications, Springer Nature Switzerland.","DOI":"10.1007\/978-3-030-16465-2"},{"key":"#cr-split#-ref_37.1","unstructured":"Publications Office of the European Union (2024). Regulation"},{"key":"#cr-split#-ref_37.2","unstructured":"(EU) 2024\/1938 of the European Parliament and of the Council of 13 June 2024 on Standards of Quality and Safety for Substances of Human Origin Intended for Human Application and Repealing Directives 2002\/98\/EC and 2004\/23\/ECText with EEA Relevance, Publications Office of the European Union."},{"key":"ref_38","unstructured":"(2022). Medical Laboratories\u2014Requirements for Quality and Competence (Standard No. ISO 15189)."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6969\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:12:56Z","timestamp":1760033576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,20]]},"references-count":39,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26146969"],"URL":"https:\/\/doi.org\/10.3390\/ijms26146969","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,20]]}}}