{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:16:54Z","timestamp":1790536614507,"version":"4.1.0"},"reference-count":66,"publisher":"IOP Publishing","issue":"4","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/iop-standard\/v1"},{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["21H03830"],"award-info":[{"award-number":["21H03830"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biofabrication"],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Stem cells can respond to mechanical stimuli such as stiffness, viscoelasticity, fluid shear stress, micropatterned geometry and hydraulic pressure. However, viscosity as an important cue is often overlooked. Thus, in this study, the influence of viscosity on trilineage differentiation (adipogenesis, chondrogenesis and osteogenesis) of human bone marrow-derived mesenchymal stem cells (hMSCs) was disclosed by three-dimensionally (3D) culturing hMSCs in viscous media. The viscosity was modulated using bioinert polyethylene glycol (PEG) at a range of 88.8\u2013645.5 cP. A cuboid agarose hydrogel container was used to encapsulate the cells and viscous media to prevent cell leakage and PEG diffusion during cell culture. Viscosity showed inhibitory effects on trilineage differentiation of hMSCs during 3D culture in viscous media containing PEG. The inhibitory effect on adipogenic and chondrogenic differentiation was stronger than that on osteogenic differentiation. Viscosity also affected cell proliferation. Viscosity strongly promoted cell proliferation during chondrogenesis, and weakly promoted cell proliferation during osteogenesis, while inhibited cell proliferation during adipogenesis. The influences of viscosity on proliferation and trilineage differentiation of hMSCs were related to the formation of cell aggregates and spheroids during 3D culture in the viscous media. The results revealed the importance of viscosity on stem cell differentiation and could provide some information for tissue engineering applications.<\/jats:p>","DOI":"10.1088\/1758-5090\/ae0661","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T22:49:18Z","timestamp":1757717358000},"page":"045016","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Influence of viscosity on bone marrow-derived mesenchymal stem cells trilineage differentiation during 3D culture"],"prefix":"10.1088","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8334-3177","authenticated-orcid":false,"given":"Chengyu","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjiao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Yoshitomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Kawazoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingnan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-3678","authenticated-orcid":true,"given":"Guoping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"bfae0661bib1","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/j.stem.2023.05.003","type":"journal-article","article-title":"Getting physical: material mechanics is an intrinsic cell cue","volume":"30","author":"Atcha","year":"2023","journal-title":"Cell Stem Cell"},{"key":"bfae0661bib2","doi-asserted-by":"publisher","first-page":"388","DOI":"10.2174\/1389450119666180831095830","type":"journal-article","article-title":"Stem cells and tissue engineering in medical practice: ethical and regulatory policies","volume":"20","author":"Sharma","year":"2019","journal-title":"Curr. Drug Targets"},{"key":"bfae0661bib3","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1021\/acsnano.2c08075","type":"journal-article","article-title":"Dissecting physical and biochemical effects in nanotopographical regulation of cell behavior","volume":"17","author":"Wang","year":"2023","journal-title":"ACS Nano"},{"key":"bfae0661bib4","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.bioactmat.2024.02.003","type":"journal-article","article-title":"Extracellular matrix stiffness as an energy metabolism regulator drives osteogenic differentiation in mesenchymal stem cells","volume":"35","author":"Na","year":"2024","journal-title":"Bioact. Mater."},{"key":"bfae0661bib5","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.120751","type":"journal-article","article-title":"Micropattern-controlled chirality of focal adhesions regulates the cytoskeletal arrangement and gene transfection of mesenchymal stem cells","volume":"271","author":"Wang","year":"2021","journal-title":"Biomaterials"},{"key":"bfae0661bib6","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/anie.202314738","type":"journal-article","article-title":"Dynamic exchange in 3D cell culture hydrogels based on crosslinking of cyclic thiosulfinates","volume":"63","author":"Janssen","year":"2024","journal-title":"Angew. Chem., Int. Ed."},{"key":"bfae0661bib7","doi-asserted-by":"publisher","first-page":"4322","DOI":"10.1039\/C9PY00862D","type":"journal-article","article-title":"Influence of ions to modulate hydrazone and oxime reaction kinetics to obtain dynamically cross-linked hyaluronic acid hydrogels","volume":"10","author":"Wang","year":"2019","journal-title":"Polym. Chem."},{"key":"bfae0661bib8","doi-asserted-by":"publisher","first-page":"4419","DOI":"10.1021\/acs.biomac.9b01100","type":"journal-article","article-title":"Oxime cross-linked alginate hydrogels with tunable stress relaxation","volume":"20","author":"S\u00e1nchez-Mor\u00e1n","year":"2019","journal-title":"Biomacromolecules"},{"key":"bfae0661bib9","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201800638","type":"journal-article","article-title":"Adaptable fast relaxing boronate-based hydrogels for probing cell\u2013matrix interactions","volume":"5","author":"Tang","year":"2018","journal-title":"Adv. Sci."},{"key":"bfae0661bib10","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202211209","type":"journal-article","article-title":"photoinduced dithiolane crosslinking for multiresponsive dynamic hydrogels","volume":"36","author":"Nelson","year":"2023","journal-title":"Adv. Mater."},{"key":"bfae0661bib11","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.biomaterials.2018.03.060","type":"journal-article","article-title":"Photopolymerized dynamic hydrogels with tunable viscoelastic properties through thioester exchange","volume":"178","author":"Brown","year":"2018","journal-title":"Biomaterials"},{"key":"bfae0661bib12","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.addr.2008.11.002","type":"journal-article","article-title":"Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues","volume":"61","author":"Lai","year":"2009","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"bfae0661bib13","doi-asserted-by":"publisher","first-page":"1978","DOI":"10.1007\/s10439-008-9577-x","type":"journal-article","article-title":"The mechanical environment of bone marrow: a review","volume":"36","author":"Gurkan","year":"2008","journal-title":"Ann. Biomed. Eng."},{"key":"bfae0661bib14","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.jmbbm.2014.09.008","type":"journal-article","article-title":"Rheological behavior of fresh bone marrow and the effects of storage","volume":"40","author":"Metzger","year":"2014","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"bfae0661bib15","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1177\/0006355X2007044002005","type":"journal-article","article-title":"Rheological properties of synovial fluids","volume":"44","author":"Fam","year":"2007","journal-title":"Biorheology"},{"key":"bfae0661bib16","doi-asserted-by":"publisher","first-page":"385","DOI":"10.3233\/bir-1987-24404","type":"journal-article","article-title":"Rheology of synovial fluid","volume":"24","author":"Schurz","year":"1987","journal-title":"Biorheology"},{"key":"bfae0661bib17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2020.105644","type":"journal-article","article-title":"Rheological properties of synovial fluid due to viscosupplements: a review for osteoarthritis remedy","volume":"196","author":"More","year":"2020","journal-title":"Comput. Methods Programs Biomed."},{"key":"bfae0661bib18","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/ar3477","type":"journal-article","article-title":"Pus: the Rodney Dangerfield of immunology","volume":"13","author":"Pisetsky","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"bfae0661bib19","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.addr.2008.09.012","type":"journal-article","article-title":"Micro- and macrorheology of mucus","volume":"61","author":"Lai","year":"2009","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"bfae0661bib20","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/s41586-022-05394-6","type":"journal-article","article-title":"Extracellular fluid viscosity enhances cell migration and cancer dissemination","volume":"611","author":"Bera","year":"2022","journal-title":"Nature"},{"key":"bfae0661bib21","doi-asserted-by":"publisher","first-page":"7713","DOI":"10.1039\/C9TB02204J","type":"journal-article","article-title":"Solution viscosity regulates chondrocyte proliferation and phenotype during 3D culture","volume":"7","author":"Lee","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"bfae0661bib22","doi-asserted-by":"publisher","first-page":"7424","DOI":"10.1039\/D3TB01174G","type":"journal-article","article-title":"3D culture of bovine articular chondrocytes in viscous medium encapsulated in agarose hydrogels for investigation of viscosity influence on cell functions","volume":"11","author":"Zheng","year":"2023","journal-title":"J. Mater. Chem. B"},{"key":"bfae0661bib23","doi-asserted-by":"publisher","first-page":"3989","DOI":"10.1039\/D2TB00729K","type":"journal-article","article-title":"Influences of viscosity on the osteogenic and adipogenic differentiation of mesenchymal stem cells with controlled morphology","volume":"10","author":"Zheng","year":"2022","journal-title":"J. Mater. Chem. B"},{"key":"bfae0661bib24","doi-asserted-by":"publisher","first-page":"267A","DOI":"10.1016\/j.bpj.2021.11.1428","type":"journal-article","article-title":"Membrane ruffling is a mechanosensor of extracellular fluid viscosity","volume":"121","author":"Pittman","year":"2022","journal-title":"Biophys. J."},{"key":"bfae0661bib25","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.biomaterials.2018.05.058","type":"journal-article","article-title":"Extracellular fluid viscosity enhances liver cancer cell mechanosensing and migration","volume":"177","author":"Gonzalez-Molina","year":"2018","journal-title":"Biomaterials"},{"key":"bfae0661bib26","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/s44286-024-00116-3","type":"journal-article","article-title":"Tuning extracellular fluid viscosity to enhance transfection efficiency","volume":"1","author":"Ma","year":"2024","journal-title":"Nat. Chem. Eng."},{"key":"bfae0661bib27","doi-asserted-by":"publisher","DOI":"10.1007\/s10409-023-23238-x","type":"journal-article","article-title":"Enhancement effects of extracellular fluid viscosity and matrix stiffness on cancer cell mechanosensing","volume":"39","author":"Cao","year":"2023","journal-title":"Acta Mech. Sin."},{"key":"bfae0661bib28","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202000617","type":"journal-article","article-title":"Osteogenic and adipogenic differentiation of mesenchymal stem cells in gelatin solutions of different viscosities","volume":"9","author":"Lee","year":"2020","journal-title":"Adv. Healthcare Mater."},{"key":"bfae0661bib29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jmst.2020.05.018","type":"journal-article","article-title":"Influence of viscosity on chondrogenic differentiation of mesenchymal stem cells during 3D culture in viscous gelatin solution-embedded hydrogels","volume":"63","author":"Lee","year":"2021","journal-title":"J. Mater. Sci. Technol."},{"key":"bfae0661bib30","doi-asserted-by":"publisher","DOI":"10.1002\/smtd.202201503","type":"journal-article","article-title":"Viscous microcapsules as microbioreactors to study mesenchymal stem\/stromal cells osteolineage commitment","volume":"7","author":"Ghasemzadeh-Hasankolaei","year":"2023","journal-title":"Small Methods"},{"key":"bfae0661bib31","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/nmat4781","type":"journal-article","article-title":"Deterministic encapsulation of single cells in thin tunable microgels for niche modelling and therapeutic delivery","volume":"16","author":"Mao","year":"2017","journal-title":"Nat. Mater."},{"key":"bfae0661bib32","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1111\/os.14026","type":"journal-article","article-title":"Biomechanical effects of mechanical stress on cells involved in fracture healing","volume":"16","author":"Wu","year":"2024","journal-title":"Orthop. Surg."},{"key":"bfae0661bib33","doi-asserted-by":"publisher","first-page":"2832","DOI":"10.1016\/j.actbio.2009.05.039","type":"journal-article","article-title":"Cell-matrix interactions and dynamic mechanical loading influence chondrocyte gene expression and bioactivity in PEG-RGD hydrogels","volume":"5","author":"Villanueva","year":"2009","journal-title":"Acta Biomater."},{"key":"bfae0661bib34","first-page":"873","type":"journal-article","article-title":"In vitro and in vivo analyses of the biological activity of RGD peptides towards Ab Bomirski melanoma","volume":"8","author":"Okroj","year":"2003","journal-title":"Cell. Mol. Biol. Lett."},{"key":"bfae0661bib35","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101058","type":"journal-article","article-title":"High-viscosity driven modulation of biomechanical properties of human mesenchymal stem cells promotes osteogenic lineage","volume":"26","author":"Chen","year":"2024","journal-title":"Mater. Today Bio"},{"key":"bfae0661bib36","doi-asserted-by":"publisher","first-page":"2809","DOI":"10.1002\/adfm.201504943","type":"journal-article","article-title":"Injectable stem cell-laden photocrosslinkable microspheres fabricated using microfluidics for rapid generation of osteogenic tissue constructs","volume":"26","author":"Zhao","year":"2016","journal-title":"Adv. Funct. Mater."},{"key":"bfae0661bib37","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2020.110798","type":"journal-article","article-title":"An efficient two-step preparation of photocrosslinked gelatin microspheres as cell carriers to support MC3T3-E1 cells osteogenic performance","volume":"188","author":"Jiang","year":"2020","journal-title":"Colloids Surf. B"},{"key":"bfae0661bib38","doi-asserted-by":"publisher","first-page":"2705","DOI":"10.1016\/j.biomaterials.2009.01.030","type":"journal-article","article-title":"3D spheroid culture system on micropatterned substrates for improved differentiation efficiency of multipotent mesenchymal stem cells","volume":"30","author":"Wang","year":"2009","journal-title":"Biomaterials"},{"key":"bfae0661bib39","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.bioactmat.2022.07.031","type":"journal-article","article-title":"Engineering the viscoelasticity of gelatin methacryloyl (GelMA) hydrogels via small \u201cdynamic bridges\u201d to regulate BMSC behaviors for osteochondral regeneration","volume":"25","author":"Liu","year":"2023","journal-title":"Bioact. Mater."},{"key":"bfae0661bib40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2024.149018","type":"journal-article","article-title":"Controlled domain gels with a wide stiffness gradient simultaneously promote bone regeneration and suppress tumor recurrence through DAPK activity","volume":"482","author":"Wang","year":"2024","journal-title":"Chem. Eng. J."},{"key":"bfae0661bib41","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.bioactmat.2021.12.005","type":"journal-article","article-title":"An overview of substrate stiffness guided cellular response and its applications in tissue regeneration","volume":"15","author":"Yi","year":"2022","journal-title":"Bioact. Mater."},{"key":"bfae0661bib42","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202300670","type":"journal-article","article-title":"Dynamic stimulations with bioengineered extracellular matrix-mimicking hydrogels for mechano cell reprogramming and therapy","volume":"10","author":"Shou","year":"2023","journal-title":"Adv. Sci."},{"key":"bfae0661bib43","doi-asserted-by":"publisher","first-page":"2188","DOI":"10.1016\/S0021-9258(18)34904-4","type":"journal-article","article-title":"Viscosity of culture medium as a regulator of synthesis and secretion of very low density lipoproteins by cultured hepatocytes","volume":"257","author":"Yedgar","year":"1982","journal-title":"J. Biol. Chem."},{"key":"bfae0661bib44","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/0304-3940(92)90048-C","type":"journal-article","article-title":"Effect of viscosity on neurite outgrowth and fractal dimension","volume":"136","author":"Caserta","year":"1992","journal-title":"Neurosci. Lett."},{"key":"bfae0661bib45","doi-asserted-by":"publisher","first-page":"5045","DOI":"10.1073\/pnas.94.10.5045","type":"journal-article","article-title":"Cell membrane fluctuations are regulated by medium macroviscosity: evidence for a metabolic driving\u2009force","volume":"94","author":"Tuvia","year":"1997","journal-title":"Proc. Natl Acad. Sci."},{"key":"bfae0661bib46","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1023\/a:1008964531534","type":"journal-article","article-title":"Image and fractal analysis of osteoblastic cells in viscous media","volume":"10","author":"Pearson","year":"1999","journal-title":"J. Mater. Sci., Mater. Med."},{"key":"bfae0661bib47","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41580-022-00556-w","type":"journal-article","article-title":"Cell\u2013extracellular matrix mechanotransduction in 3D","volume":"24","author":"Saraswathibhatla","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"bfae0661bib48","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202307554","type":"journal-article","article-title":"Osmolar modulation drives reversible cell cycle exit and human pluripotent cell differentiation via NF-\u03ba\u0412 and WNT signaling","volume":"11","author":"Chui","year":"2024","journal-title":"Adv. Sci."},{"key":"bfae0661bib49","doi-asserted-by":"publisher","first-page":"5598","DOI":"10.1039\/D4BM00710G","type":"journal-article","article-title":"Influence of viscosity on adipogenic and osteogenic differentiation of mesenchymal stem cells during 2D culture","volume":"12","author":"Lu","year":"2024","journal-title":"Biomater. Sci."},{"key":"bfae0661bib50","doi-asserted-by":"publisher","first-page":"eadr5023","DOI":"10.1126\/sciadv.adr5023","type":"journal-article","article-title":"Extracellular fluid viscosity regulates human mesenchymal stem cell lineage and function","volume":"11","author":"Amitrano","year":"2025","journal-title":"Sci. Adv."},{"key":"bfae0661bib51","doi-asserted-by":"publisher","first-page":"6128","DOI":"10.1038\/s41467-022-33683-1","type":"journal-article","article-title":"Polarized NHE1 and SWELL1 regulate migration direction, efficiency and metastasis","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat. Commun."},{"key":"bfae0661bib52","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1073\/pnas.2103228118","type":"journal-article","article-title":"Passive coupling of membrane tension and cell volume during active response of cells to osmosis","volume":"118","author":"Roffay","year":"2021","journal-title":"Proc. Natl Acad. Sci."},{"key":"bfae0661bib53","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.bioactmat.2021.07.020","type":"journal-article","article-title":"Microgel assembly: fabrication, characteristics and application in tissue engineering and regenerative medicine","volume":"9","author":"Feng","year":"2022","journal-title":"Bioact. Mater."},{"key":"bfae0661bib54","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/nm1576","type":"journal-article","article-title":"Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets","volume":"13","author":"Ohashi","year":"2007","journal-title":"Nat. Med."},{"key":"bfae0661bib55","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/S1369-7021(04)00234-2","type":"journal-article","article-title":"Cell sheet engineering","volume":"7","author":"Yamato","year":"2004","journal-title":"Mater. Today"},{"key":"bfae0661bib56","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.bioactmat.2020.08.014","type":"journal-article","article-title":"Advancing application of mesenchymal stem cell-based bone tissue regeneration","volume":"6","author":"Shang","year":"2021","journal-title":"Bioact. Mater."},{"key":"bfae0661bib57","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2024.342413","type":"journal-article","article-title":"Review: 3D cell models for organ-on-a-chip applications","volume":"1301","author":"\u017buchowska","year":"2024","journal-title":"Anal. Chim. Acta"},{"key":"bfae0661bib58","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1002\/biot.200700228","type":"journal-article","article-title":"Recent advances in three-dimensional multicellular spheroid culture for biomedical research","volume":"3","author":"Lin","year":"2008","journal-title":"Biotechnol. J."},{"key":"bfae0661bib59","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1007\/s12015-020-10006-9","type":"journal-article","article-title":"Specificity of 3D MSC spheroids microenvironment: impact on MSC behavior and properties","volume":"16","author":"Jaukovi\u0107","year":"2020","journal-title":"Stem Cell Rev. Rep."},{"key":"bfae0661bib60","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.3390\/biomedicines11041049","type":"journal-article","article-title":"3D spheroid cultivation alters the extent and progression of osteogenic differentiation of mesenchymal stem\/stromal cells compared to 2D cultivation","volume":"11","author":"Wolff","year":"2023","journal-title":"Biomedicines"},{"key":"bfae0661bib61","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.3390\/cells11081313","type":"journal-article","article-title":"A comparative study on the adipogenic differentiation of mesenchymal stem\/stromal cells in 2D and 3D culture","volume":"11","author":"Wolff","year":"2022","journal-title":"Cells"},{"key":"bfae0661bib62","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ddtec.2017.03.002","type":"journal-article","article-title":"The production of 3D tumor spheroids for cancer drug discov.","volume":"23","author":"Sant","year":"2017","journal-title":"Drug Discov. Today"},{"key":"bfae0661bib63","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s13770-020-00265-5","type":"journal-article","article-title":"Hypoxia pretreatment promotes chondrocyte differentiation of human adipose-derived stem cells via vascular endothelial growth factor","volume":"17","author":"Hwang","year":"2020","journal-title":"Tissue Eng. Regen. Med."},{"key":"bfae0661bib64","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s13287-015-0014-4","type":"journal-article","article-title":"HIF-1A and C\/EBPs transcriptionally regulate adipogenic differentiation of bone marrow-derived MSCs in hypoxia","volume":"6","author":"Jiang","year":"2015","journal-title":"Stem Cell Res. Ther."},{"key":"bfae0661bib65","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023965","type":"journal-article","article-title":"Hypoxia inhibits osteogenesis in human mesenchymal stem cells through direct regulation of RUNX2 by TWIST","volume":"6","author":"Yang","year":"2011","journal-title":"PLoS One"},{"key":"bfae0661bib66","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202205487","type":"journal-article","article-title":"Steering stem cell fate within 3D living composite tissues using stimuli-responsive cell-adhesive micromaterials","volume":"10","author":"Kamperman","year":"2023","journal-title":"Adv. Sci."}],"container-title":["Biofabrication"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ae0661","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ae0661\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ae0661","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ae0661\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ae0661\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ae0661\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ae0661\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ae0661\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T12:44:59Z","timestamp":1758631499000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ae0661"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,23]]},"references-count":66,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,9,23]]},"published-print":{"date-parts":[[2025,10,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1758-5090\/ae0661","relation":{},"ISSN":["1758-5082","1758-5090"],"issn-type":[{"value":"1758-5082","type":"print"},{"value":"1758-5090","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,23]]},"assertion":[{"value":"Influence of viscosity on bone marrow-derived mesenchymal stem cells trilineage differentiation during 3D culture","name":"article_title","label":"Article Title"},{"value":"Biofabrication","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2024-12-20","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-09-12","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-09-23","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}