{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T20:45:42Z","timestamp":1793997942321,"version":"4.8.0"},"reference-count":90,"publisher":"IOP Publishing","issue":"1","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100003452","name":"Innovation and Technology Commission","doi-asserted-by":"crossref","award":["Health@InnoHK"],"award-info":[{"award-number":["Health@InnoHK"]}],"id":[{"id":"10.13039\/501100003452","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"crossref","award":["ECS (24204819)"],"award-info":[{"award-number":["ECS (24204819)"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research and Development Program of China","award":["2018YFA0903400"],"award-info":[{"award-number":["2018YFA0903400"]}]},{"DOI":"10.13039\/501100004853","name":"The Chinese University of Hong Kong","doi-asserted-by":"crossref","award":["8601014"],"award-info":[{"award-number":["8601014"]}],"id":[{"id":"10.13039\/501100004853","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biofabrication"],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Liver tissue engineering is promising as an alternative strategy to treat liver failure. However, generating functional hepatocytes from stem cells is conventionally restricted by the immature status of differentiated cells. Besides, embedding hepatocytes in bulk scaffold is limited by a lack of vascularity and low cell-packing density. Here, we fabricate collagen type I (COL1) microspheres for efficient hepatic differentiation of pluripotent stem cells and subsequent assembly of prevascularized liver tissue (PLT). Using a microfluidic platform, we demonstrate that hydrogel COL1 microspheres (mCOL1) encapsulating human embryonic stem cells (hESCs) can be reproducibly generated and efficiently differentiated into hepatocyte-like cells (HLCs) microspheres for the first time. Compared with other culture configurations such as encapsulation of hESC in a bulk COL1 hydrogel and 2D monolayer culture, mCOL1 with high uniformity produce HLC microspheres of improved maturity based on comprehensive analyses of cell morphology, transcriptome profile, hepatic marker expression and hepatic functions. In addition, these HLC microspheres can be applied as building blocks to self-assemble with endothelial cells to construct a dense PLT. The PLT resembles native liver tissue with high cell-packing density, shows successful engraftment in mice liver following implantation, and exhibits improved hepatic function\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Overall, it is believed that this multiscale technology will advance the fabrication of stem cell-based liver tissue for regenerative medicine, drug screening, and\n                    <jats:italic>in vitro<\/jats:italic>\n                    liver modeling.\n                  <\/jats:p>","DOI":"10.1088\/1758-5090\/aca79b","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T17:25:00Z","timestamp":1669829100000},"page":"015016","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Efficient hepatic differentiation of hydrogel microsphere-encapsulated human pluripotent stem cells for engineering prevascularized liver tissue"],"prefix":"10.1088","volume":"15","author":[{"given":"Shuai","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuerao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyang","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2052-9724","authenticated-orcid":true,"given":"Yi-Ping","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0486-360X","authenticated-orcid":false,"given":"Wayne Yuk-Wai","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-9573","authenticated-orcid":false,"given":"Jiansu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0573-1251","authenticated-orcid":true,"given":"Hon Fai","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"bfaca79bbib1","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1097\/TP.0000000000003550","article-title":"Liver transplantation in acute-on-chronic liver failure","volume":"105","author":"Karvellas","year":"2021","journal-title":"Transplantation"},{"key":"bfaca79bbib2","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/j.jhep.2021.03.030","article-title":"Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: results of the ELITA\/EF-CLIF collaborative study (ECLIS)","volume":"75","author":"Belli","year":"2021","journal-title":"J. Hepatol."},{"key":"bfaca79bbib3","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1053\/j.gastro.2008.02.092","article-title":"Live donors in liver transplantation","volume":"134","author":"Brown","year":"2008","journal-title":"Gastroenterology"},{"key":"bfaca79bbib4","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s13770-019-00178-y","article-title":"Stem cell-based therapies for liver diseases: an overview and update","volume":"16","author":"Wang","year":"2019","journal-title":"Tissue Eng. Regen. Med."},{"key":"bfaca79bbib5","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/nrgastro.2010.44","article-title":"Human hepatocyte transplantation: current experience and future challenges","volume":"7","author":"Dhawan","year":"2010","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"bfaca79bbib6","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/pr.2017.284","article-title":"Human hepatocyte transplantation for liver disease: current status and future perspectives","volume":"83","author":"Iansante","year":"2018","journal-title":"Pediatr. Res."},{"key":"bfaca79bbib7","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.biomaterials.2017.11.027","article-title":"A decade of progress in liver regenerative medicine","volume":"157","author":"Zhang","year":"2018","journal-title":"Biomaterials"},{"key":"bfaca79bbib8","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201909553","article-title":"Engineering liver microtissues for disease modeling and regenerative medicine","volume":"30","author":"Huang","year":"2020","journal-title":"Adv. Funct. Mater."},{"key":"bfaca79bbib9","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201901435","article-title":"Advanced biomaterials and processing methods for liver regeneration: state-of-the-art and future trends","volume":"9","author":"da Silva Morais","year":"2020","journal-title":"Adv. Healthcare Mater."},{"key":"bfaca79bbib10","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/ac2b89","article-title":"Efficient fabrication of monodisperse hepatocyte spheroids and encapsulation in hybrid hydrogel with controllable extracellular matrix effect","volume":"14","author":"Deng","year":"2021","journal-title":"Biofabrication"},{"key":"bfaca79bbib11","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s00204-012-0983-3","article-title":"Primary hepatocyte cultures for pharmaco-toxicological studies: at the busy crossroad of various anti-dedifferentiation strategies","volume":"87","author":"Fraczek","year":"2013","journal-title":"Arch. Toxicol."},{"key":"bfaca79bbib12","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/bioengineering7020047","article-title":"Hepatic differentiation of stem cells in 2D and 3D biomaterial systems","volume":"7","author":"Zhao","year":"2020","journal-title":"Bioengineering"},{"key":"bfaca79bbib13","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1016\/j.biomaterials.2012.11.029","article-title":"3D spheroid culture of hESC\/hiPSC-derived hepatocyte-like cells for drug toxicity testing","volume":"34","author":"Takayama","year":"2013","journal-title":"Biomaterials"},{"key":"bfaca79bbib14","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107711","article-title":"Assembly and function of a bioengineered human liver for transplantation generated solely from induced pluripotent stem cells","volume":"31","author":"Takeishi","year":"2020","journal-title":"Cell Rep."},{"key":"bfaca79bbib15","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmt.2020.100730","article-title":"Regulation of hepatic differentiation of human embryonic stem cells by calcium silicate extracts for liver injury repairing","volume":"20","author":"Zheng","year":"2020","journal-title":"Appl. Mater. Today"},{"key":"bfaca79bbib16","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1002\/term.2659","article-title":"Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering","volume":"12","author":"Starokozhko","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"bfaca79bbib17","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108455","article-title":"Large-scale generation of functional and transplantable hepatocytes and cholangiocytes from human endoderm stem cells","volume":"33","author":"Feng","year":"2020","journal-title":"Cell Rep."},{"key":"bfaca79bbib18","doi-asserted-by":"publisher","first-page":"566","DOI":"10.21037\/atm.2020.02.164","article-title":"Induced pluripotent stem cells for the treatment of liver diseases: challenges and perspectives from a clinical viewpoint","volume":"8","author":"Pareja","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"bfaca79bbib19","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.scr.2016.03.009","article-title":"Hepatic differentiation of human pluripotent stem cells in miniaturized format suitable for high-throughput screen","volume":"16","author":"Carpentier","year":"2016","journal-title":"Stem Cell Res."},{"key":"bfaca79bbib20","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/j.stemcr.2015.04.001","article-title":"Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells","volume":"4","author":"Siller","year":"2015","journal-title":"Stem Cell Rep."},{"key":"bfaca79bbib21","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s13287-022-02831-1","article-title":"Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy","volume":"13","author":"Pan","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"bfaca79bbib22","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13287-018-0794-4","article-title":"Highly efficient and expedited hepatic differentiation from human pluripotent stem cells by pure small-molecule cocktails","volume":"9","author":"Du","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"bfaca79bbib23","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.stemcr.2022.01.003","article-title":"Leveraging interacting signaling pathways to robustly improve the quality and yield of human pluripotent stem cell-derived hepatoblasts and hepatocytes","volume":"17","author":"Raggi","year":"2022","journal-title":"Stem Cell Rep."},{"key":"bfaca79bbib24","doi-asserted-by":"publisher","DOI":"10.1242\/bio.042192","article-title":"Collagen vitrigel promotes hepatocytic differentiation of induced pluripotent stem cells into functional hepatocyte-like cells","volume":"8","author":"Nakai","year":"2019","journal-title":"Biol Open"},{"key":"bfaca79bbib25","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120529","article-title":"Generation of uniform liver spheroids from human pluripotent stem cells for imaging-based drug toxicity analysis","volume":"269","author":"Lee","year":"2021","journal-title":"Biomaterials"},{"key":"bfaca79bbib26","doi-asserted-by":"publisher","first-page":"8443","DOI":"10.1002\/jcp.27769","article-title":"Biomaterial aided differentiation and maturation of induced pluripotent stem cells","volume":"234","author":"Velmurugan","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"bfaca79bbib27","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.3892\/ijmm.2017.3190","article-title":"Hepatic differentiation of human iPSCs in different 3D models: a comparative study","volume":"40","author":"Meier","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"bfaca79bbib28","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.diff.2019.02.006","article-title":"The role of cellular interactions in the induction of hepatocyte polarity and functional maturation in stem cell-derived hepatic cells","volume":"106","author":"Blau","year":"2019","journal-title":"Differentiation"},{"key":"bfaca79bbib29","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.jcyt.2017.08.008","article-title":"Three-dimensional hydrogel culture conditions promote the differentiation of human induced pluripotent stem cells into hepatocytes","volume":"20","author":"Luo","year":"2018","journal-title":"Cytotherapy"},{"key":"bfaca79bbib30","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3390\/bioengineering6040113","article-title":"Engineered 3D polymer and hydrogel microenvironments for cell culture applications","volume":"6","author":"Fan","year":"2019","journal-title":"Bioengineering"},{"key":"bfaca79bbib31","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201701165","article-title":"Engineering 3D hydrogels for personalized in vitro human tissue models","volume":"7","author":"Liaw","year":"2018","journal-title":"Adv. Healthcare Mater."},{"key":"bfaca79bbib32","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41578-019-0148-6","article-title":"Hydrogel microparticles for biomedical applications","volume":"5","author":"Daly","year":"2020","journal-title":"Nat. Rev. Mater."},{"key":"bfaca79bbib33","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1002\/adhm.201500279","article-title":"Biotunable acoustic node assembly of organoids","volume":"4","author":"Chen","year":"2015","journal-title":"Adv. Healthcare Mater."},{"key":"bfaca79bbib34","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s40005-019-00433-3","article-title":"Injectable hydrogels for islet transplantation: a concise review","volume":"50","author":"Shrestha","year":"2020","journal-title":"J. Pharm. Invest."},{"key":"bfaca79bbib35","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.actbio.2021.10.037","article-title":"Droplet microfluidics-based biomedical microcarriers","volume":"138","author":"Shao","year":"2021","journal-title":"Acta Biomater."},{"key":"bfaca79bbib36","doi-asserted-by":"publisher","first-page":"4482","DOI":"10.1039\/C6LC01193D","article-title":"Cell-laden microfluidic microgels for tissue regeneration","volume":"16","author":"Jiang","year":"2016","journal-title":"Lab Chip"},{"key":"bfaca79bbib37","doi-asserted-by":"publisher","first-page":"3941","DOI":"10.1039\/C5LC00785B","article-title":"Cell-sized condensed collagen microparticles for preparing microengineered composite spheroids of primary hepatocytes","volume":"15","author":"Yamada","year":"2015","journal-title":"Lab Chip"},{"key":"bfaca79bbib38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3727\/105221620X15868728381608","article-title":"Microscale collagen and fibroblast interactions enhance primary human hepatocyte functions in three-dimensional models","volume":"20","author":"Kukla","year":"2020","journal-title":"Gene Expr."},{"key":"bfaca79bbib39","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/978-1-4939-7021-6_20","article-title":"Microfluidic-based generation of 3D collagen spheres to investigate multicellular spheroid invasion","volume":"vol 1612","author":"Bertillot","year":"2017"},{"key":"bfaca79bbib40","doi-asserted-by":"publisher","first-page":"3277","DOI":"10.1039\/c2lc40558j","article-title":"Collagen microsphere production on a chip","volume":"12","author":"Hong","year":"2012","journal-title":"Lab Chip"},{"key":"bfaca79bbib41","first-page":"435","article-title":"Manipulation of cells and cell spheroids using collagen hydrogel microbeads prepared by microfluidic devices","author":"Sugaya","year":"2012"},{"key":"bfaca79bbib42","doi-asserted-by":"publisher","first-page":"3462","DOI":"10.1038\/srep03462","article-title":"Rapid formation of multicellular spheroids in double-emulsion droplets with controllable microenvironment","volume":"3","author":"Chan","year":"2013","journal-title":"Sci. Rep."},{"key":"bfaca79bbib43","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.actbio.2016.01.012","article-title":"Microfluidic fabrication of bioactive microgels for rapid formation and enhanced differentiation of stem cell spheroids","volume":"34","author":"Siltanen","year":"2016","journal-title":"Acta Biomater."},{"key":"bfaca79bbib44","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.120818","article-title":"Engineered cardiac tissue microsphere production through direct differentiation of hydrogel-encapsulated human pluripotent stem cells","volume":"274","author":"Finklea","year":"2021","journal-title":"Biomaterials"},{"key":"bfaca79bbib45","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1186\/s12967-019-02137-6","article-title":"Current progress in hepatic tissue regeneration by tissue engineering","volume":"17","author":"Hosseini","year":"2019","journal-title":"J. Transl. Med."},{"key":"bfaca79bbib46","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.smim.2017.06.001","article-title":"In vivo cellular reactions to different biomaterials\u2014physiological and pathological aspects and their consequences","volume":"29","author":"Al-Maawi","year":"2017","journal-title":"Semin. Immunol."},{"key":"bfaca79bbib47","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/S1369-7021(08)70089-0","article-title":"Biomaterials engineered for integration","volume":"11","author":"Moroni","year":"2008","journal-title":"Mater. Today"},{"key":"bfaca79bbib48","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202102087","article-title":"Medical applications of porous biomaterials: features of porosity and tissue-specific implications for biocompatibility","volume":"11","author":"Hernandez","year":"2022","journal-title":"Adv. Healthcare Mater."},{"key":"bfaca79bbib49","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1089\/ten.teb.2009.0639","article-title":"Controlling the porosity and microarchitecture of hydrogels for tissue engineering","volume":"16","author":"Annabi","year":"2010","journal-title":"Tissue Eng. B"},{"key":"bfaca79bbib50","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.actbio.2019.04.050","article-title":"Micro-injection molded, poly(vinyl alcohol)-calcium salt templates for precise customization of 3D hydrogel internal architecture","volume":"95","author":"McNulty","year":"2019","journal-title":"Acta Biomater."},{"key":"bfaca79bbib51","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.bioactmat.2017.10.001","article-title":"3D bioactive composite scaffolds for bone tissue engineering","volume":"3","author":"Turnbull","year":"2018","journal-title":"Bioact. Mater."},{"key":"bfaca79bbib52","doi-asserted-by":"publisher","first-page":"3178","DOI":"10.3390\/polym13183178","article-title":"Progress of 3D bioprinting in organ manufacturing","volume":"13","author":"Song","year":"2021","journal-title":"Polymers"},{"key":"bfaca79bbib53","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1007\/s00204-021-03212-y","article-title":"3D bioprinting of complex tissues in vitro: state-of-the-art and future perspectives","volume":"96","author":"Xiang","year":"2022","journal-title":"Arch. Toxicol."},{"key":"bfaca79bbib54","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201703156","article-title":"Multicellular vascularized engineered tissues through user-programmable biomaterial photodegradation","volume":"29","author":"Arakawa","year":"2017","journal-title":"Adv. Mater."},{"key":"bfaca79bbib55","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.biotechadv.2015.12.004","article-title":"Prevascularization in tissue engineering: current concepts and future directions","volume":"34","author":"Laschke","year":"2016","journal-title":"Biotechnol. Adv."},{"key":"bfaca79bbib56","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201907670","article-title":"Designing microgels for cell culture and controlled assembly of tissue microenvironments","volume":"30","author":"Caldwell","year":"2020","journal-title":"Adv. Funct. Mater."},{"key":"bfaca79bbib57","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1016\/j.biomaterials.2008.12.084","article-title":"Organ printing: tissue spheroids as building blocks","volume":"30","author":"Mironov","year":"2009","journal-title":"Biomaterials"},{"key":"bfaca79bbib58","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1089\/ten.teb.2020.0093","article-title":"Engineered prevascularization for oral tissue grafting: a systematic review","volume":"26","author":"Smirani","year":"2020","journal-title":"Tissue Eng. B"},{"key":"bfaca79bbib59","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s10544-019-0423-8","article-title":"Three-dimensional cultured liver-on-a-chip with mature hepatocyte-like cells derived from human pluripotent stem cells","volume":"21","author":"Kamei","year":"2019","journal-title":"Biomed. Microdevices"},{"key":"bfaca79bbib60","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121006","article-title":"A fully defined matrix to support a pluripotent stem cell derived multi-cell-liver steatohepatitis and fibrosis model","volume":"276","author":"Kumar","year":"2021","journal-title":"Biomaterials"},{"key":"bfaca79bbib61","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/nprot.2009.234","article-title":"Soft lithography for micro- and nanoscale patterning","volume":"5","author":"Qin","year":"2010","journal-title":"Nat. Protocols"},{"key":"bfaca79bbib62","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6439\/aa7e92","article-title":"Molecular and functional assessment of multicellular cancer spheroids produced in double emulsions enabled by efficient airway resistance based selective surface treatment","volume":"27","author":"Ma","year":"2017","journal-title":"J. Micromech. Microeng."},{"key":"bfaca79bbib63","doi-asserted-by":"publisher","first-page":"eaah5505","DOI":"10.1126\/scitranslmed.aah5505","article-title":"In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease","volume":"9","author":"Stevens Kelly","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"bfaca79bbib64","doi-asserted-by":"publisher","first-page":"2720","DOI":"10.1002\/smll.201502932","article-title":"Efficient one-step production of microencapsulated hepatocyte spheroids with enhanced functions","volume":"12","author":"Chan","year":"2016","journal-title":"Small"},{"key":"bfaca79bbib65","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1016\/j.stemcr.2015.10.016","article-title":"Recombinant laminins drive the differentiation and self-organization of hESC-derived hepatocytes","volume":"5","author":"Cameron","year":"2015","journal-title":"Stem Cell Rep."},{"key":"bfaca79bbib66","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1002\/ar.1092420307","article-title":"Ultrastructural and functional differentiation of hepatocytes under long-term culture conditions","volume":"242","author":"Knop","year":"1995","journal-title":"Anat. Rec."},{"key":"bfaca79bbib67","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.yexcr.2016.11.027","article-title":"Functional properties of hepatocytes in vitro are correlated with cell polarity maintenance","volume":"350","author":"Zeigerer","year":"2017","journal-title":"Exp. Cell Res."},{"key":"bfaca79bbib68","doi-asserted-by":"publisher","first-page":"2655","DOI":"10.1089\/ten.tea.2012.0681","article-title":"Characterizing the effects of heparin gel stiffness on function of primary hepatocytes","volume":"19","author":"You","year":"2013","journal-title":"Tissue Eng. A"},{"key":"bfaca79bbib69","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1111\/liv.12134","article-title":"Liver tissue engineering and cell sources: issues and challenges","volume":"33","author":"Palakkan","year":"2013","journal-title":"Liver Int."},{"key":"bfaca79bbib70","doi-asserted-by":"publisher","first-page":"265","DOI":"10.3389\/fmed.2019.00265","article-title":"iPSC-derived hepatocytes as a platform for disease modeling and drug discovery","volume":"6","author":"Corbett","year":"2019","journal-title":"Front. Med."},{"key":"bfaca79bbib71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086372","article-title":"Maturation of induced pluripotent stem cell derived hepatocytes by 3D-culture","volume":"9","author":"Gieseck","year":"2014","journal-title":"PLoS One"},{"key":"bfaca79bbib72","doi-asserted-by":"crossref","DOI":"10.1101\/2020.12.02.406835","article-title":"Scalable production of tissue-like vascularised liver organoids from human PSCs","author":"Harrison","year":"2020"},{"key":"bfaca79bbib73","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1271\/bbb.60568","article-title":"Production of mouse embryoid bodies with hepatic differentiation potential by stirred tank bioreactor","volume":"71","author":"Yin","year":"2007","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"bfaca79bbib74","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1002\/bit.20086","article-title":"Modeling mass transfer in hepatocyte spheroids via cell viability, spheroid size, and hepatocellular functions","volume":"86","author":"Glicklis","year":"2004","journal-title":"Biotechnol. Bioeng."},{"key":"bfaca79bbib75","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1097\/MOT.0b013e3283329d53","article-title":"The effects of low oxygen on self-renewal and differentiation of embryonic stem cells","volume":"14","author":"Millman","year":"2009","journal-title":"Curr. Opin. Organ. Transplant."},{"key":"bfaca79bbib76","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s12079-018-0456-4","article-title":"Oxygen drives hepatocyte differentiation and phenotype stability in liver cell lines","volume":"12","author":"van Wenum","year":"2018","journal-title":"J. Cell Commun. Signal"},{"key":"bfaca79bbib77","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1089\/scd.2013.0097","article-title":"Spheroid culture for enhanced differentiation of human embryonic stem cells to hepatocyte-like cells","volume":"23","author":"Subramanian","year":"2014","journal-title":"Stem Cells Dev."},{"key":"bfaca79bbib78","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.3727\/096368913X667484","article-title":"Strategies for short-term storage of hepatocytes for repeated clinical infusions","volume":"23","author":"Jorns","year":"2014","journal-title":"Cell Transplant."},{"key":"bfaca79bbib79","doi-asserted-by":"publisher","first-page":"685","DOI":"10.3727\/096368912X655163","article-title":"Cells and materials for liver tissue engineering","volume":"22","author":"Li","year":"2013","journal-title":"Cell Transplant."},{"key":"bfaca79bbib80","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1073\/pnas.1524510113","article-title":"Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting","volume":"113","author":"Ma","year":"2016","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"bfaca79bbib81","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201905505","article-title":"Bioprinting of multiscaled hepatic lobules within a highly vascularized construct","volume":"16","author":"Kang","year":"2020","journal-title":"Small"},{"key":"bfaca79bbib82","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12951-019-0458-2","article-title":"Indoor nanoscale particulate matter-induced coagulation abnormality based on a human 3D microvascular model on a microfluidic chip","volume":"17","author":"Li","year":"2019","journal-title":"J. Nanobiotechnol."},{"key":"bfaca79bbib83","doi-asserted-by":"publisher","first-page":"3215","DOI":"10.1073\/pnas.1522273113","article-title":"Morphogenesis of 3D vascular networks is regulated by tensile forces","volume":"113","author":"Rosenfeld","year":"2016","journal-title":"Proc. Natl Acad. Sci."},{"key":"bfaca79bbib84","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature12271","article-title":"Vascularized and functional human liver from an iPSC-derived organ bud transplant","volume":"499","author":"Takebe","year":"2013","journal-title":"Nature"},{"key":"bfaca79bbib85","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.1016\/j.celrep.2017.11.005","article-title":"Massive and reproducible production of liver buds entirely from human pluripotent stem cells","volume":"21","author":"Takebe","year":"2017","journal-title":"Cell Rep."},{"key":"bfaca79bbib86","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1089\/ten.tea.2008.0314","article-title":"Prevascularization of a fibrin-based tissue construct accelerates the formation of functional anastomosis with host vasculature","volume":"15","author":"Chen","year":"2008","journal-title":"Tissue Eng. A"},{"key":"bfaca79bbib87","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.3727\/096368910X492571","article-title":"Prevascular structures promote vascularization in engineered human adipose tissue constructs upon implantation","volume":"19","author":"Verseijden","year":"2010","journal-title":"Cell Transplant."},{"key":"bfaca79bbib88","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/ab8f36","article-title":"Functional evaluation of prevascularization in one-stage versus two-stage tissue engineering approach of human bio-artificial muscle","volume":"12","author":"Gholobova","year":"2020","journal-title":"Biofabrication"},{"key":"bfaca79bbib89","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1089\/ars.2013.5697","article-title":"Extracellular matrix and liver disease","volume":"21","author":"Arriazu","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"bfaca79bbib90","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1089\/ten.2005.11.1718","article-title":"Injectable liver: a novel approach using fibrin gel as a matrix for culture and intrahepatic transplantation of hepatocytes","volume":"11","author":"Bruns","year":"2005","journal-title":"Tissue Eng."}],"container-title":["Biofabrication"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/aca79b","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/aca79b\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/aca79b","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/aca79b\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/aca79b\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/aca79b\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/aca79b\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/aca79b\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T07:02:37Z","timestamp":1671174157000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/aca79b"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,16]]},"references-count":90,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12,16]]},"published-print":{"date-parts":[[2023,1,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1758-5090\/aca79b","relation":{},"ISSN":["1758-5082","1758-5090"],"issn-type":[{"value":"1758-5082","type":"print"},{"value":"1758-5090","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,16]]},"assertion":[{"value":"Efficient hepatic differentiation of hydrogel microsphere-encapsulated human pluripotent stem cells for engineering prevascularized liver tissue","name":"article_title","label":"Article Title"},{"value":"Biofabrication","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2022 The Author(s). Published by IOP Publishing Ltd","name":"copyright_information","label":"Copyright Information"},{"value":"2022-07-27","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2022-11-30","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2022-12-16","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}