{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:56:16Z","timestamp":1790283376732,"version":"4.1.0"},"reference-count":38,"publisher":"IOP Publishing","issue":"1","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/page\/copyright"},{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"crossref","award":["2021R1A2C2004981"],"award-info":[{"award-number":["2021R1A2C2004981"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"crossref","award":["20012378"],"award-info":[{"award-number":["20012378"]}],"id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biofabrication"],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Managing type 1 diabetes mellitus (T1DM) presents significant challenges because of the complexity of replicating the microenvironment of pancreatic islets and ensuring the long-term viability and function of transplanted insulin-producing cells (IPCs). This study developed a functional approach that utilizes 3D bioprinting technology to create pore-enriched and pre-vascularized tissue constructs incorporating a pancreatic tissue-derived decellularized extracellular matrix and human-induced pluripotent stem cells (hiPSCs) aimed at enhancing blood glucose regulation in T1DM. We designed a volumetric 3D pancreatic tissue construct that supported the engraftment, survival, and insulin-producing functionality of hiPSC-derived IPCs. The construct\u2019s porosity was optimized to enhance IPC delivery efficiency. Additionally, human umbilical vein endothelial cells co-cultured with IPCs in a patterned structure facilitated pre-vascularization, improving construct integration with host tissues and accelerating revascularization post-transplantation. Our results demonstrate high cell viability and sustained insulin production in diabetic rodent models, indicating the constructs\u2019 effectiveness in regulating blood glucose levels over an extended period. The findings of this study not only underscore the potential of 3D bioprinting for creating functional tissue constructs for T1DM treatment but also offer efficient cell delivery techniques applicable to other areas of regenerative medicine.<\/jats:p>","DOI":"10.1088\/1758-5090\/ad998e","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T23:01:36Z","timestamp":1733180496000},"page":"015034","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Engineering pore-enriched and pre-vascularized volumetric constructs for enhanced blood glucose regulation in type 1 diabetes therapy"],"prefix":"10.1088","volume":"17","author":[{"given":"Jaewook","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Kyong","family":"Shim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Na","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myungji","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Gyu","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonggwon","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhun","family":"Chae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisoo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song Cheol","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5869-4330","authenticated-orcid":true,"given":"Dong-Woo","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9046-3495","authenticated-orcid":true,"given":"Jinah","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"bfad998ebib1","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1007\/s11892-013-0433-5","article-title":"The emerging global epidemic of type 1 diabetes","volume":"13","author":"Tuomilehto","year":"2013","journal-title":"Curr. Diab. Rep."},{"key":"bfad998ebib2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2017.16","article-title":"Type 1 diabetes mellitus","volume":"3","author":"Katsarou","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"bfad998ebib3","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/S0140-6736(13)60591-7","article-title":"Type 1 diabetes","volume":"383","author":"Atkinson","year":"2014","journal-title":"Lancet"},{"key":"bfad998ebib4","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s13300-019-00743-7","article-title":"Insulin therapy in adults with type 1 diabetes mellitus: a narrative review","volume":"11","author":"Jane\u017e","year":"2020","journal-title":"Diabetes Therapy"},{"key":"bfad998ebib5","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1001\/jama.2017.13994","article-title":"Association of insulin pump therapy vs insulin injection therapy with severe hypoglycemia, ketoacidosis, and glycemic control among children, adolescents, and young adults with type 1 diabetes","volume":"318","author":"Karges","year":"2017","journal-title":"JAMA"},{"key":"bfad998ebib6","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/nrendo.2013.138","article-title":"The current state of pancreas transplantation","volume":"9","author":"Gruessner","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"bfad998ebib7","doi-asserted-by":"publisher","first-page":"211","DOI":"10.2147\/DMSO.S50789","article-title":"Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges","volume":"7","author":"Bruni","year":"2014","journal-title":"Diabetes Metabolic Syndrome Obesity Targets Ther."},{"key":"bfad998ebib8","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1056\/NEJM200007273430401","article-title":"Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen","volume":"343","author":"Shapiro","year":"2000","journal-title":"New Engl. J. Med."},{"key":"bfad998ebib9","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1016\/S0140-6736(18)31320-5","article-title":"Type 1 diabetes","volume":"391","author":"DiMeglio","year":"2018","journal-title":"Lancet"},{"key":"bfad998ebib10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11892-019-1166-x","article-title":"Bioprinting an artificial pancreas for type 1 diabetes","volume":"19","author":"Kim","year":"2019","journal-title":"Curr. Diab. Rep."},{"key":"bfad998ebib11","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1557\/s43577-021-00260-8","article-title":"Three-dimensional bioprinting with decellularized extracellular matrix-based bioinks in translational regenerative medicine","volume":"47","author":"Chae","year":"2022","journal-title":"MRS Bull."},{"key":"bfad998ebib12","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1039\/C8TB02787K","article-title":"3D cell printing of islet-laden pancreatic tissue-derived extracellular matrix bioink constructs for enhancing pancreatic functions","volume":"7","author":"Kim","year":"2019","journal-title":"J. Mat. Chem. B"},{"key":"bfad998ebib13","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1930261","article-title":"Oxidative stress in pancreatic beta cell regeneration","volume":"2017","author":"Wang","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"bfad998ebib14","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1161\/CIRCRESAHA.111.249243","article-title":"Immunogenicity of pluripotent stem cells and their derivatives","volume":"112","author":"de Almeida","year":"2013","journal-title":"Circ. Res."},{"key":"bfad998ebib15","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/nature10135","article-title":"Immunogenicity of induced pluripotent stem cells","volume":"474","author":"Zhao","year":"2011","journal-title":"Nature"},{"key":"bfad998ebib16","doi-asserted-by":"publisher","first-page":"9337","DOI":"10.1073\/pnas.1619216114","article-title":"Modular tissue engineering for the vascularization of subcutaneously transplanted pancreatic islets","volume":"114","author":"Vlahos","year":"2017","journal-title":"Proc. Natl Acad. Sci."},{"key":"bfad998ebib17","doi-asserted-by":"publisher","DOI":"10.3389\/ti.2021.10214","article-title":"Bio-engineering of pre-vascularized islet organoids for the treatment of type 1 diabetes","volume":"35","author":"Wassmer","year":"2022","journal-title":"Transpl. Int."},{"key":"bfad998ebib18","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1210\/endo-127-1-126","article-title":"Establishment of a pancreatic \u03b2 cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms","volume":"127","author":"Miyazaki","year":"1990","journal-title":"Endocrinology"},{"key":"bfad998ebib19","doi-asserted-by":"publisher","first-page":"E773","DOI":"10.1152\/ajpendo.2000.279.4.E773","article-title":"Insulin secretion and differential gene expression in glucose-responsive and-unresponsive MIN6 sublines","volume":"279","author":"Minami","year":"2000","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"bfad998ebib20","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.scr.2011.10.002","article-title":"Small molecules induce efficient differentiation into insulin-producing cells from human induced pluripotent stem cells","volume":"8","author":"Kunisada","year":"2012","journal-title":"Stem Cell Res."},{"key":"bfad998ebib21","doi-asserted-by":"publisher","DOI":"10.3791\/60434","article-title":"Pancreatic tissue-derived extracellular matrix bioink for printing 3D cell-laden pancreatic tissue constructs","volume":"154","author":"Kim","year":"2019","journal-title":"J. Vis. Exp."},{"key":"bfad998ebib22","doi-asserted-by":"publisher","first-page":"e78","DOI":"10.1002\/cpz1.78","article-title":"Streptozotocin\u2010induced diabetic models in mice and rats","volume":"1","author":"Furman","year":"2021","journal-title":"Curr. Protoc."},{"key":"bfad998ebib23","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1507\/endocrj.K10E-399","article-title":"Postprandial serum C-peptide to plasma glucose ratio as a predictor of subsequent insulin treatment in patients with type 2 diabetes","volume":"58","author":"Saisho","year":"2011","journal-title":"Endocr. J."},{"key":"bfad998ebib24","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1080\/19382014.2020.1763719","article-title":"Characterization of a mouse model of islet transplantation using MIN-6 cells","volume":"12","author":"Sobel","year":"2020","journal-title":"Islets"},{"key":"bfad998ebib25","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/s42255-020-0269-7","article-title":"Islet transplantation in the subcutaneous space achieves long-term euglycaemia in preclinical models of type 1 diabetes","volume":"2","author":"Yu","year":"2020","journal-title":"Nat. Metab."},{"key":"bfad998ebib26","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41536-022-00262-3","article-title":"Co-transplantation of pancreatic islets and microvascular fragments effectively restores normoglycemia in diabetic mice","volume":"7","author":"Wrublewsky","year":"2022","journal-title":"npj Regen. Med."},{"key":"bfad998ebib27","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/S0168-3659(02)00008-1","article-title":"Biodegradable injectable in situ forming drug delivery systems","volume":"80","author":"Hatefi","year":"2002","journal-title":"J. Control. Release"},{"key":"bfad998ebib28","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1081\/E-EBPP-120050057","article-title":"Chitosan and pluronic\u00ae F-127: pharmaceutical applications","volume":"11","author":"Dom\u00ednguez-Delgado","year":"2016","journal-title":"Encyclopedia Biomed. Polym. Polym. Biomater."},{"key":"bfad998ebib29","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1002\/term.1769","article-title":"Co\u2010culture of adipose\u2010derived stem cells and endothelial cells in fibrin induces angiogenesis and vasculogenesis in a chorioallantoic membrane model","volume":"10","author":"Strassburg","year":"2016","journal-title":"J. Tissue Eng. Regener. Med."},{"key":"bfad998ebib30","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.3390\/jcm8101602","article-title":"Human umbilical vein endothelial cells (HUVECs) co-culture with osteogenic cells: from molecular communication to engineering prevascularised bone grafts","volume":"8","author":"Kocherova","year":"2019","journal-title":"J. Clin. Med."},{"key":"bfad998ebib31","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1089\/ten.tea.2015.0317","article-title":"Coculturing human islets with proangiogenic support cells to improve islet revascularization at the subcutaneous transplantation site","volume":"22","author":"Buitinga","year":"2016","journal-title":"Tissue Eng. A"},{"key":"bfad998ebib32","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1007\/BF00401058","article-title":"Pancreatic beta cell line MIN6 exhibits characteristics of glucose metabolism and glucose-stimulated insulin secretion similar to those of normal islets","volume":"36","author":"Ishihara","year":"1993","journal-title":"Diabetologia"},{"key":"bfad998ebib33","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.stem.2009.09.008","article-title":"Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2","volume":"5","author":"Giorgetti","year":"2009","journal-title":"Cell Stem Cell"},{"key":"bfad998ebib34","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/mt.2012.245","article-title":"Intrapatient variations in type 1 diabetes-specific iPS cell differentiation into insulin-producing cells","volume":"21","author":"Thatava","year":"2013","journal-title":"Mol. Ther."},{"key":"bfad998ebib35","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1007\/s00592-015-0726-z","article-title":"Human induced pluripotent stem cells differentiate into insulin-producing cells able to engraft in vivo","volume":"52","author":"Pellegrini","year":"2015","journal-title":"Acta Diabetol."},{"key":"bfad998ebib36","first-page":"3490","article-title":"Real-time observation of pancreatic beta cell differentiation from human induced pluripotent stem cells","volume":"11","author":"Wang","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"bfad998ebib37","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.967765","article-title":"In depth functional characterization of human induced pluripotent stem cell-derived beta cells in vitro and in vivo","volume":"10","author":"Fantuzzi","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"bfad998ebib38","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120627","article-title":"Recent advances in the design of implantable insulin secreting heterocellular islet organoids","volume":"269","author":"Akolpoglu","year":"2021","journal-title":"Biomaterials"}],"container-title":["Biofabrication"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ad998e","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ad998e\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ad998e","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ad998e\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ad998e\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ad998e\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ad998e\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ad998e\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T05:51:44Z","timestamp":1734328304000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1758-5090\/ad998e"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,16]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12,16]]},"published-print":{"date-parts":[[2025,1,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1758-5090\/ad998e","relation":{},"ISSN":["1758-5082","1758-5090"],"issn-type":[{"value":"1758-5082","type":"print"},{"value":"1758-5090","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,16]]},"assertion":[{"value":"Engineering pore-enriched and pre-vascularized volumetric constructs for enhanced blood glucose regulation in type 1 diabetes therapy","name":"article_title","label":"Article Title"},{"value":"Biofabrication","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2024 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":"2024-05-21","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-12-02","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-12-16","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}