{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:06:57Z","timestamp":1788901617948,"version":"build-2803163510"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Iron overload-related osteoporosis has garnered significant attention, yet its pathological mechanisms remain unclear. Traditional two-dimensional (2D) culture systems often fail to recapitulate the extracellular matrix (ECM) microenvironment, leading to discrepancies between in vitro and in vivo findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a three-dimensional (3D) culture system using methacrylated gelatin (GelMA) microspheres to culture preosteoblastic cells, simulate the bone microenvironment under iron overload conditions, and systematically examine changes in cellular morphology, viability, function, and gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Iron overload impaired cell viability, induced oxidative stress, and inhibited osteogenesis in both 2D and 3D cultures. However, cells in 3D exhibited enhanced resilience, including reduced ROS levels, higher viability, preserved cytoskeletal integrity, and less apoptosis and G1-phase arrest. Compared to 2D, 3D-cultured cells showed downregulated expression of ITGA1 and ITGB1, decreased adhesion function, and promoted proliferation. Transcriptomics further revealed activation of NF-\u03baB signaling and DNA replication pathways in 3D, while key pathways such as Hippo, focal adhesion, and Wnt were suppressed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The GelMA microsphere-based 3D system provides a physiologically relevant model for studying iron overload. These findings offer not only mechanistic insights but also suggest potential microenvironment-targeted therapeutic strategies for iron overload-associated osteoporosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbioe.2026.1700858","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:51:55Z","timestamp":1769064715000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects and mechanisms of iron overload on the proliferation and differentiation of preosteoblastic cells via a 3D microsphere culture system"],"prefix":"10.3389","volume":"14","author":[{"given":"Yu","family":"Pan","sequence":"first","affiliation":[{"name":"Research Institute of Tissue Engineering and Stem Cells, Department of Clinical Lab, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renfeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Research Institute of Tissue Engineering and Stem Cells, Department of Clinical Lab, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengdong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Institute of Tissue Engineering and Stem Cells, Department of Clinical Lab, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuwei","family":"Luo","sequence":"additional","affiliation":[{"name":"Research Institute of Tissue Engineering and Stem Cells, Department of Clinical Lab, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Feng","sequence":"additional","affiliation":[{"name":"Research Institute of Tissue Engineering and Stem Cells, Department of Clinical Lab, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongqin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Research Institute of Tissue Engineering and Stem Cells, Department of Clinical Lab, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.3390\/life12111792","article-title":"The regulation of the hippo pathway by intercellular junction proteins","volume":"12","author":"Ahmad","year":"2022","journal-title":"Life"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.tranon.2023.101849","article-title":"DLK1-DIO3 region as a source of tumor suppressor miRNAs in papillary thyroid carcinoma","volume":"46","author":"Alves","year":"2024","journal-title":"Transl. Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1080\/03630269.2022.2158100","article-title":"Prediction of heart and liver iron overload in \u03b2-Thalassemia major patients using machine learning methods","volume":"46","author":"Asmarian","year":"2022","journal-title":"Hemoglobin"},{"key":"B4","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.tem.2022.06.004","article-title":"Iron effects versus metabolic alterations in hereditary hemochromatosis driven bone loss","volume":"33","author":"Baschant","year":"2022","journal-title":"Trends Endocrinol. & Metabolism"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2022.36.S1.0R360","article-title":"Determining the role of the Ras family GTPase Rap1 in regulating mTORC2 activity and function in cell migration","volume":"36","author":"Cahigas","year":"2022","journal-title":"FASEB J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"16468","DOI":"10.1021\/acsami.4c18787","article-title":"Decoupling of density-dependent migration\/proliferation dichotomy on surface potential gradient","volume":"17","author":"Chen","year":"2025","journal-title":"ACS Appl. Mater. & Interfaces"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.3390\/cells10071624","article-title":"The voltage-gated sodium channel Beta4 subunit maintains epithelial phenotype in mammary cells","volume":"10","author":"Doray","year":"2021","journal-title":"Cells"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3586","DOI":"10.1039\/C7TB00041C","article-title":"Microporous density-mediated response of MSCs on 3D trimodal macro\/micro\/nano-porous scaffolds via fibronectin\/integrin and FAK\/MAPK signaling pathways","volume":"5","author":"Duan","year":"2017","journal-title":"J. Mater. Chem. B"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbalip.2022.159181","article-title":"Type I collagen reduces lipid accumulation during adipogenesis of preadipocytes 3T3-L1 via the YAP-mTOR-autophagy axis","volume":"1867","author":"Gao","year":"2022","journal-title":"Biochimica Biophysica Acta (BBA) - Mol. Cell Biol. Lipids"},{"key":"B10","doi-asserted-by":"publisher","first-page":"344","DOI":"10.3390\/biomimetics8040344","article-title":"Substrate stiffness of bone microenvironment controls functions of pre-osteoblasts and fibroblasts in vitro","volume":"8","author":"Gao","year":"2023","journal-title":"Biomimetics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/pharmaceutics12121215","article-title":"Three-dimensional human cell culture models to study the pathophysiology of the anterior eye","volume":"12","author":"Garc\u00eda-Posadas","year":"2020","journal-title":"Pharmaceutics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0323283","article-title":"A comprehensive protocol for PDMS fabrication for use in cell culture","volume":"20","author":"Greaney","year":"2025","journal-title":"PLOS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1016\/j.csbj.2020.07.016","article-title":"Boolean model of anchorage dependence and contact inhibition points to coordinated inhibition but semi-independent induction of proliferation and migration","volume":"15","author":"Guberman","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"121097","DOI":"10.1016\/j.biomaterials.2021.121097","article-title":"Myoblast mechanotransduction and myotube morphology is dependent on BAG3 regulation of YAP and TAZ","volume":"277","author":"G\u00fcnay","year":"2021","journal-title":"Biomaterials"},{"key":"B15","doi-asserted-by":"publisher","first-page":"111135","DOI":"10.1016\/j.cbi.2024.111135","article-title":"Exogenous iron caused osteocyte apoptosis, increased RANKL production, and stimulated bone resorption through oxidative stress in a murine model","volume":"399","author":"Guo","year":"2024","journal-title":"Chemico-Biological Interact."},{"key":"B16","doi-asserted-by":"publisher","first-page":"7194","DOI":"10.1021\/acsabm.4c00800","article-title":"3D scaffold-based culture system enhances preclinical evaluation of natural killer cell therapy in A549 lung cancer cells","volume":"7","author":"Han","year":"2024","journal-title":"ACS Appl. Bio Mater."},{"key":"B17","doi-asserted-by":"publisher","first-page":"5086","DOI":"10.1002\/jcp.27312","article-title":"YAP regulates periodontal ligament cell differentiation into myofibroblast interacted with RhoA\/ROCK pathway","volume":"234","author":"He","year":"2019","journal-title":"J. Cell. Physiology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2300395","DOI":"10.1002\/adhm.202300395","article-title":"Gelatin methacryloyl hydrogel, from standardization, performance, to biomedical application","volume":"12","author":"He","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1088\/1748-605X\/ad651c","article-title":"Fe-doped 45S5 bioactive glass compositions impair the metabolic activity and proliferation of metastatic human breast cancer cells in vitro","volume":"19","author":"Hildenbrand","year":"2024","journal-title":"Biomed. Mater."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1002\/iub.2656","article-title":"Iron overload\u2010induced ferroptosis of osteoblasts inhibits osteogenesis and promotes osteoporosis: an in vitro and in vivo study","volume":"74","author":"Jiang","year":"2022","journal-title":"IUBMB Life"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e2307388","DOI":"10.1002\/advs.202307388","article-title":"Ferroptosis in osteocytes as a target for protection against postmenopausal osteoporosis","volume":"11","author":"Jiang","year":"2024","journal-title":"Adv. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"032006","DOI":"10.1088\/1758-5090\/add95f","article-title":"Advances in microfluidic biofabrication technology for bone metastasis modeling","volume":"17","author":"Khanmohammadi","year":"2025","journal-title":"Biofabrication"},{"key":"B23","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.jare.2023.08.012","article-title":"Harnessing the dental cells derived from human induced pluripotent stem cells for hard tissue engineering","volume":"61","author":"Kim","year":"2024","journal-title":"J. Adv. Res."},{"key":"B24","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/978-4-431-56550-5_22","article-title":"Regulation of skeletal myoblast differentiation by drebrin","volume-title":"Drebrin","author":"Krauss","year":"2017"},{"key":"B25","doi-asserted-by":"publisher","first-page":"361","DOI":"10.2174\/0115733971273691231121131455","article-title":"New emerging aspect of herbal extracts for the treatment ofOsteoporosis: overview","volume":"20","author":"Kumari","year":"2024","journal-title":"Curr. Rheumatol. Rev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"3396","DOI":"10.1016\/j.bioactmat.2021.03.013","article-title":"3D printed silk-gelatin hydrogel scaffold with different porous structure and cell seeding strategy for cartilage regeneration","volume":"6","author":"Li","year":"2021","journal-title":"Bioact. Mater."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/adhm.202403006","article-title":"Composite scaffold materials of nanocerium oxide doped with allograft bone: dual optimization based on anti\u2010inflammatory properties and promotion of osteogenic mineralization","volume":"14","author":"Li","year":"2025","journal-title":"Adv. Healthc. Mater."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/2634431","article-title":"Ferroptosis: a new regulatory mechanism in osteoporosis","volume":"2022","author":"Liu","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B29","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.immuni.2017.03.019","article-title":"Glutathione primes T cell metabolism for inflammation","volume":"46","author":"Mak","year":"2017","journal-title":"Immunity"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/biom13071062","article-title":"3D bioprinting of a bioactive composite scaffold for cell delivery in periodontal tissue regeneration","volume":"13","author":"Miao","year":"2023","journal-title":"Biomolecules"},{"key":"B31","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s11136-023-03542-7","article-title":"Quality of life in postmenopausal women with osteoporosis and osteopenia: associations with bone microarchitecture and nutritional status","volume":"33","author":"Mornar","year":"2024","journal-title":"Qual. Life Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13048-021-00892-z","article-title":"The challenge of ovarian tissue culture: 2D versus 3D culture","volume":"14","author":"Pais","year":"2021","journal-title":"J. Ovarian Res."},{"key":"B33","first-page":"6381","article-title":"Iron overload induces ferroptosis and inhibits osteogenic differentiation in preosteoblasts","volume":"29","author":"Pan","year":"2025","journal-title":"Chin. J. Tissue Eng. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e2928","DOI":"10.1002\/iub.2928","article-title":"Depletion of macrophages and osteoclast precursors mitigates iron overload\u2010mediated bone loss","volume":"77","author":"Passin","year":"2025","journal-title":"IUBMB Life"},{"key":"B35","doi-asserted-by":"publisher","first-page":"691","DOI":"10.3390\/diagnostics14070691","article-title":"Multiparametric cardiac magnetic resonance assessment in sickle beta thalassemia","volume":"14","author":"Pistoia","year":"2024","journal-title":"Diagnostics"},{"key":"B36","doi-asserted-by":"publisher","first-page":"109407","DOI":"10.1016\/j.jnutbio.2023.109407","article-title":"Dynamic chromatin accessibility during nutritional iron overload reveals a BMP6-independent induction of cell cycle genes","volume":"119","author":"Radushkevitz-Frishman","year":"2023","journal-title":"J. Nutr. Biochem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1002\/jbmr.2323","article-title":"N-cadherin restrains PTH activation of Lrp6\/\u03b2-catenin signaling and osteoanabolic action","volume":"30","author":"Revollo","year":"2015","journal-title":"J. Bone Mineral Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/s41413-024-00365-1","article-title":"DNMT aberration-incurred GPX4 suppression prompts osteoblast ferroptosis and osteoporosis","volume":"12","author":"Ruan","year":"2024","journal-title":"Bone Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1073\/pnas.2219854120","article-title":"Mechanosensitive stem cell fate choice is instructed by dynamic fluctuations in activation of Rho GTPases","volume":"120","author":"Sampayo","year":"2023","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"20342","DOI":"10.1002\/anie.202105425","article-title":"Non\u2010invasive regulation of cellular morphology using a photoswitchable mechanical DNA polymer","volume":"60","author":"Sethi","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2022.108168","article-title":"Advances in pathogenesis and therapeutic strategies for osteoporosis","volume":"237","author":"Song","year":"2022","journal-title":"Pharmacol. & Ther."},{"key":"B42","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.actbio.2021.11.030","article-title":"Development of a bi-layered cryogenic electrospun polylactic acid scaffold to study calcific aortic valve disease in a 3D co-culture model","volume":"140","author":"Stadelmann","year":"2022","journal-title":"Acta Biomater."},{"key":"B43","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.engreg.2023.02.003","article-title":"Supplemental mineral ions for bone regeneration and osteoporosis treatment","volume":"4","author":"Su","year":"2023","journal-title":"Eng. Regen."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1002\/cbin.12075","article-title":"Significance of cell culture phases for utilizing 3D cultures of A549 cells for in vitro studies","volume":"47","author":"Swethaa","year":"2023","journal-title":"Cell Biol. Int."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.intimp.2024.113016","article-title":"Protocatechualdehyde inhibits iron overload-induced bone loss by inhibiting inflammation and oxidative stress in senile rats","volume":"141","author":"Tao","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3630","DOI":"10.1021\/acsomega.2c06052","article-title":"Spheroid engineering in microfluidic devices","volume":"8","author":"Tevlek","year":"2023","journal-title":"ACS Omega"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/1295382","article-title":"ROS-mediated necroptosis is involved in iron overload-induced osteoblastic cell death","volume":"2020","author":"Tian","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/biomimetics7030101","article-title":"Effect of menin deletion in early osteoblast lineage on the mineralization of an in vitro 3D osteoid-like dense collagen gel matrix","volume":"7","author":"Troka","year":"2022","journal-title":"Biomimetics"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.apmt.2022.101582","article-title":"Recent advances in organoid engineering: a comprehensive review","volume":"29","author":"Unagolla","year":"2022","journal-title":"Appl. Mater. Today"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jbmrpl\/ziae064","article-title":"Iron and bones: effects of iron overload, deficiency and anemia treatments on bone","volume":"8","author":"Von Brackel","year":"2024","journal-title":"JBMR Plus"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.msec.2020.111822","article-title":"ChondroGELesis: hydrogels to harness the chondrogenic potential of stem cells","volume":"121","author":"Walker","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12967-023-04563-z","article-title":"Romosozumab in osteoporosis: yesterday, today and tomorrow","volume":"21","author":"Wu","year":"2023","journal-title":"J. Transl. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"15668","DOI":"10.1002\/jcp.28217","article-title":"Iron overload threatens the growth of osteoblast cells via inhibiting the PI3K\/AKT\/FOXO3a\/DUSP14 signaling pathway","volume":"234","author":"Xia","year":"2019","journal-title":"J. Cell. Physiology"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12951-025-03253-w","article-title":"Biopolymer-based bone scaffold for controlled Pt (IV) prodrug release and synergistic photothermal-chemotherapy and immunotherapy in osteosarcoma","volume":"23","author":"Yan","year":"2025","journal-title":"J. Nanobiotechnology"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.redox.2025.103727","article-title":"Revised model for cell cycle regulation by iron: differential roles between transferrin and ferritin","volume":"85","author":"Yanagiya","year":"2025","journal-title":"Redox Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"C298","DOI":"10.1152\/ajpcell.00913.2024","article-title":"The stiffness of extracellular matrix in regulating cellular metabolism","volume":"329","author":"Zha","year":"2025","journal-title":"Am. J. Physiology-Cell Physiology"},{"key":"B57","doi-asserted-by":"publisher","first-page":"12704","DOI":"10.1038\/s41598-024-63613-8","article-title":"YAP promotes the early development of temporomandibular joint bony ankylosis by regulating mesenchymal stem cell function","volume":"14","author":"Zhang","year":"2024","journal-title":"Sci. Rep."},{"key":"B58","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1186\/s40001-025-02666-5","article-title":"Matrix stiffness enhances viability, migration, invasion and invadopodia formation of oral cancer cells via PI3K\/AKT pathway in vitro","volume":"30","author":"Zhang","year":"2025","journal-title":"Eur. J. Med. Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/smll.202401400","article-title":"Droplet microfluidics powered hydrogel microparticles for stem cell\u2010mediated biomedical applications","volume":"20","author":"Zheng","year":"2024","journal-title":"Small"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1111\/jcmm.12946","article-title":"3D culture increases pluripotent gene expression in mesenchymal stem cells through relaxation of cytoskeleton tension","volume":"21","author":"Zhou","year":"2017","journal-title":"J. Cell. Mol. Med."}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2026.1700858\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T07:42:49Z","timestamp":1771918969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2026.1700858\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":60,"alternative-id":["10.3389\/fbioe.2026.1700858"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2026.1700858","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]},"article-number":"1700858"}}