{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:53:51Z","timestamp":1781718831395,"version":"3.54.5"},"reference-count":77,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["22A0205L1"],"award-info":[{"award-number":["22A0205L1"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS-2023-00272815"],"award-info":[{"award-number":["RS-2023-00272815"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2022M3A9G8017220"],"award-info":[{"award-number":["2022M3A9G8017220"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS-2025-0230364"],"award-info":[{"award-number":["RS-2025-0230364"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Controlled Release"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.jconrel.2026.114798","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T16:29:00Z","timestamp":1772728140000},"page":"114798","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Bioengineered hybrid spheroids integrating mesenchymal stem cells and metformin-loaded microspheres for the treatment of sepsis-induced liver injury"],"prefix":"10.1016","volume":"393","author":[{"given":"Dinesh","family":"Chaudhary","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabyya","family":"Kausar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeonghye","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manju","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhyeung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Seok","family":"Youn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Oh","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Yeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simmyung","family":"Yook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee-Heon","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jconrel.2026.114798_bb0005","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/s41551-023-01050-0","article-title":"Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells","volume":"7","author":"Schrijver","year":"2023","journal-title":"Nat. Biomed. Eng."},{"key":"10.1016\/j.jconrel.2026.114798_bb0010","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrgastro.2016.168","article-title":"Liver\u2014guardian, modifier and target of sepsis","volume":"14","author":"Strnad","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0015","doi-asserted-by":"crossref","first-page":"1429370","DOI":"10.3389\/fmed.2024.1429370","article-title":"Molecular mechanisms of Sepsis attacking the immune system and solid organs","volume":"11","author":"Yang","year":"2024","journal-title":"Front. Med."},{"key":"10.1016\/j.jconrel.2026.114798_bb0020","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1038\/s41467-025-57706-9","article-title":"PD-L1+ plasma cells suppress T lymphocyte responses in patients with sepsis and mouse sepsis models","volume":"16","author":"Gossez","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jconrel.2026.114798_bb0025","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1136\/jech-2012-200977","article-title":"Withdrawal of \u2018Xigris\u2019 from the market: old and new lessons","volume":"66","author":"Poole","year":"2012","journal-title":"J. Epidemiol. Community Health"},{"key":"10.1016\/j.jconrel.2026.114798_bb0030","doi-asserted-by":"crossref","first-page":"eaaz6980","DOI":"10.1126\/sciadv.aaz6980","article-title":"Exosome-based delivery of super-repressor I\u03baB\u03b1 relieves sepsis-associated organ damage and mortality","volume":"6","author":"Choi","year":"2020","journal-title":"Sci. Adv."},{"key":"10.1016\/j.jconrel.2026.114798_bb0035","doi-asserted-by":"crossref","first-page":"eadu4034","DOI":"10.1126\/sciadv.adu4034","article-title":"Fluoxetine promotes IL-10\u2013dependent metabolic defenses to protect from sepsis-induced lethality","volume":"11","author":"Gallant","year":"2025","journal-title":"Sci. Adv."},{"key":"10.1016\/j.jconrel.2026.114798_bb0040","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2020.107476","article-title":"Immunotherapy in sepsis-brake or accelerate?","volume":"208","author":"Steinhagen","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.jconrel.2026.114798_bb0045","article-title":"Sepsis: pathophysiology and clinical management","volume":"353","author":"Gotts","year":"2016","journal-title":"Bmj"},{"key":"10.1016\/j.jconrel.2026.114798_bb0050","doi-asserted-by":"crossref","first-page":"1557323","DOI":"10.3389\/fsci.2025.1557323","article-title":"Transforming sepsis heterogeneity: challenges and progress","volume":"3","author":"Dellinger","year":"2025","journal-title":"Front. Sci."},{"key":"10.1016\/j.jconrel.2026.114798_bb0055","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1164\/rccm.201710-2068ED","article-title":"Cell-based therapy in sepsis. A step closer","volume":"197","author":"Gotts","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.jconrel.2026.114798_bb0060","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1097\/ALN.0000000000001882","article-title":"Stem cell\u2013based therapies for sepsis","volume":"127","author":"Keane","year":"2017","journal-title":"Anesthesiology"},{"key":"10.1016\/j.jconrel.2026.114798_bb0065","doi-asserted-by":"crossref","first-page":"7837837","DOI":"10.1155\/2022\/7837837","article-title":"Differential lung protective capacity of exosomes derived from human adipose tissue, bone marrow, and umbilical cord mesenchymal stem cells in sepsis-induced acute lung injury","volume":"2022","author":"Deng","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"10.1016\/j.jconrel.2026.114798_bb0070","doi-asserted-by":"crossref","first-page":"2500637","DOI":"10.1002\/advs.202500637","article-title":"Engineering extracellular vesicles derived from 3D cultivation of BMSCs enriched with HGF ameliorate Sepsis-induced lung epithelial barrier damage","volume":"12","author":"Chen","year":"2025","journal-title":"Adv. Sci."},{"key":"10.1016\/j.jconrel.2026.114798_bb0075","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-019-1337-3","article-title":"Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN\/LPS-induced fulminant hepatic toxicity","volume":"10","author":"Regmi","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"10.1016\/j.jconrel.2026.114798_bb0080","doi-asserted-by":"crossref","first-page":"1136964","DOI":"10.3389\/fimmu.2023.1136964","article-title":"Mesenchymal stem cell-derived exosomes for treatment of sepsis","volume":"14","author":"Homma","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0085","doi-asserted-by":"crossref","first-page":"1010399","DOI":"10.3389\/fimmu.2022.1010399","article-title":"Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells","volume":"13","author":"Sarsenova","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0090","doi-asserted-by":"crossref","first-page":"2405662","DOI":"10.1002\/advs.202405662","article-title":"Biomimetic vascularized iPSC-hepatocyte spheroids for liver regeneration","volume":"12","author":"Wang","year":"2025","journal-title":"Adv. Sci."},{"key":"10.1016\/j.jconrel.2026.114798_bb0095","doi-asserted-by":"crossref","first-page":"2004856","DOI":"10.1002\/advs.202004856","article-title":"A microfluidic multisize spheroid array for multiparametric screening of anticancer drugs and blood\u2013brain barrier transport properties","volume":"8","author":"Eilenberger","year":"2021","journal-title":"Adv. Sci."},{"key":"10.1016\/j.jconrel.2026.114798_bb0100","first-page":"1","article-title":"Emerging biotechnologies for engineering liver organoids","volume":"45","author":"Zhao","year":"2025","journal-title":"Bioact. Mater."},{"key":"10.1016\/j.jconrel.2026.114798_bb0105","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.111078","article-title":"Metformin potentiates immunosuppressant activity and adipogenic differentiation of human umbilical cord-mesenchymal stem cells","volume":"124","author":"Bajetto","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0110","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1002\/term.3142","article-title":"Metformin enhances osteogenic differentiation of stem cells from human exfoliated deciduous teeth through AMPK pathway","volume":"14","author":"Zhao","year":"2020","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"10.1016\/j.jconrel.2026.114798_bb0115","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1093\/rheumatology\/kez631","article-title":"Metformin enhances the immunomodulatory potential of adipose-derived mesenchymal stem cells through STAT1 in an animal model of lupus","volume":"59","author":"Jang","year":"2020","journal-title":"Rheumatology"},{"key":"10.1016\/j.jconrel.2026.114798_bb0120","doi-asserted-by":"crossref","first-page":"1465697","DOI":"10.3389\/fphar.2024.1465697","article-title":"Metformin-mediated effects on mesenchymal stem cells and mechanisms: proliferation, differentiation and aging","volume":"15","author":"Liu","year":"2024","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0125","doi-asserted-by":"crossref","first-page":"1779346","DOI":"10.1155\/2022\/1779346","article-title":"Preconditioning and engineering strategies for improving the efficacy of mesenchymal stem cell-derived exosomes in cell-free therapy","volume":"2022","author":"Chen","year":"2022","journal-title":"Stem Cells Int."},{"key":"10.1016\/j.jconrel.2026.114798_bb0130","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1080\/22221751.2022.2045876","article-title":"Metformin attenuated sepsis-related liver injury by modulating gut microbiota","volume":"11","author":"Liang","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"10.1016\/j.jconrel.2026.114798_bb0135","first-page":"469","article-title":"Metformin-attenuated sepsis-induced oxidative damages: a novel role for metformin","volume":"21","author":"Ghavimi","year":"2018","journal-title":"Iran. J. Basic Med. Sci."},{"key":"10.1016\/j.jconrel.2026.114798_bb0140","doi-asserted-by":"crossref","first-page":"4598","DOI":"10.1080\/21655979.2022.2036305","article-title":"Metformin attenuated sepsis-associated liver injury and inflammatory response in aged mice","volume":"13","author":"Song","year":"2022","journal-title":"Bioengineered"},{"key":"10.1016\/j.jconrel.2026.114798_bb0145","first-page":"363","article-title":"A review on the protective effects of metformin in sepsis-induced organ failure","volume":"21","author":"Hassan","year":"2019","journal-title":"Cell J."},{"key":"10.1016\/j.jconrel.2026.114798_bb0150","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.intimp.2016.10.002","article-title":"AMPK activation by metformin inhibits local innate immune responses in the isolated rat heart by suppression of TLR 4-related pathway","volume":"40","author":"Vaez","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2021.120752","article-title":"Heterospheroid formation improves therapeutic efficacy of mesenchymal stem cells in murine colitis through immunomodulation and epithelial regeneration","volume":"271","author":"Regmi","year":"2021","journal-title":"Biomaterials"},{"key":"10.1016\/j.jconrel.2026.114798_bb0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2024.130356","article-title":"Fabrication of stem cell heterospheroids with sustained-release chitosan and poly (lactic-co-glycolic acid) microspheres to guide cell fate toward chondrogenic differentiation","volume":"263","author":"Nguyen","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0165","doi-asserted-by":"crossref","first-page":"eabn8614","DOI":"10.1126\/sciadv.abn8614","article-title":"Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation","volume":"8","author":"Nguyen","year":"2022","journal-title":"Sci. Adv."},{"key":"10.1016\/j.jconrel.2026.114798_bb0170","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-1-61737-960-4_3","article-title":"Isolation of murine adipose-derived stem cells","volume":"702","author":"Yu","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.xpro.2020.100086","article-title":"Protocol for primary mouse hepatocyte isolation","volume":"1","author":"Charni-Natan","year":"2020","journal-title":"STAR Protoc."},{"key":"10.1016\/j.jconrel.2026.114798_bb0180","first-page":"e53069","article-title":"Protocol for isolation of primary human hepatocytes and corresponding major populations of non-parenchymal liver cells","volume":"109","author":"Kegel","year":"2016","journal-title":"J. Vis. Exp."},{"key":"10.1016\/j.jconrel.2026.114798_bb0185","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1080\/15548627.2020.1850608","article-title":"Enhanced viability and function of mesenchymal stromal cell spheroids is mediated via autophagy induction","volume":"17","author":"Regmi","year":"2021","journal-title":"Autophagy"},{"key":"10.1016\/j.jconrel.2026.114798_bb0190","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0294236","article-title":"SRplot: a free online platform for data visualization and graphing","volume":"18","author":"Tang","year":"2023","journal-title":"PLoS One"},{"key":"10.1016\/j.jconrel.2026.114798_bb0195","doi-asserted-by":"crossref","first-page":"7227","DOI":"10.1016\/j.biomaterials.2013.05.079","article-title":"A microparticle approach to morphogen delivery within pluripotent stem cell aggregates","volume":"34","author":"Bratt-Leal","year":"2013","journal-title":"Biomaterials"},{"key":"10.1016\/j.jconrel.2026.114798_bb0200","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.actbio.2017.08.003","article-title":"Engineering cell aggregates through incorporated polymeric microparticles","volume":"62","author":"Ahrens","year":"2017","journal-title":"Acta Biomater."},{"key":"10.1016\/j.jconrel.2026.114798_bb0205","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1021\/acs.molpharmaceut.1c00125","article-title":"Inhalable porous microspheres loaded with metformin and docosahexaenoic acid suppress tumor metastasis by modulating premetastatic niche","volume":"18","author":"Chen","year":"2021","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.jconrel.2026.114798_bb0210","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.4314\/tjpr.v17i7.1","article-title":"Influence of drug-polymer ratio on physical characteristics and release of metformin hydrochloride from metforminalginate microspheres","volume":"17","author":"Hariyadi","year":"2018","journal-title":"Trop. J. Pharm. Res."},{"key":"10.1016\/j.jconrel.2026.114798_bb0215","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jconrel.2013.02.029","article-title":"Delivery of definable number of drug or growth factor loaded poly (dl-lactic acid-co-glycolic acid) microparticles within human embryonic stem cell derived aggregates","volume":"168","author":"Qutachi","year":"2013","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2026.114798_bb0220","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2023-081120","article-title":"Metformin for sepsis-associated AKI: a protocol for the randomized clinical trial of the safety and FeasibiLity of metformin as a treatment for sepsis-associated AKI (LiMiT AKI)","volume":"14","author":"Saraiva","year":"2024","journal-title":"BMJ Open"},{"key":"10.1016\/j.jconrel.2026.114798_bb0225","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4049\/jimmunol.1800006","article-title":"Metformin augments anti-inflammatory and chondroprotective properties of mesenchymal stem cells in experimental osteoarthritis","volume":"203","author":"Park","year":"2019","journal-title":"J. Immunol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0230","article-title":"Metformin stimulates FGF21 expression in primary hepatocytes","volume":"2012","author":"Nygaard","year":"2012","journal-title":"J. Diabetes Res."},{"key":"10.1016\/j.jconrel.2026.114798_bb0235","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1211\/jpp.60.12.0017","article-title":"Metformin regulates osteoblast and adipocyte differentiation of rat mesenchymal stem cells","volume":"60","author":"Gao","year":"2008","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0240","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1007\/s00125-017-4336-x","article-title":"Metformin: clinical use in type 2 diabetes","volume":"60","author":"Sanchez-Rangel","year":"2017","journal-title":"Diabetologia"},{"key":"10.1016\/j.jconrel.2026.114798_bb0245","doi-asserted-by":"crossref","first-page":"7848","DOI":"10.1021\/acsabm.1c00796","article-title":"Construction of hybrid cell spheroids using cell-sized cross-linked nanogel microspheres as an artificial extracellular matrix","volume":"4","author":"Hayashi","year":"2021","journal-title":"ACS Appl. Bio Mater."},{"key":"10.1016\/j.jconrel.2026.114798_bb0250","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s13287-023-03435-z","article-title":"Hybrid spheroids containing mesenchymal stem cells promote therapeutic angiogenesis by increasing engraftment of co-transplanted endothelial colony-forming cells in vivo","volume":"14","author":"Song","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"10.1016\/j.jconrel.2026.114798_bb0255","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.actbio.2017.10.022","article-title":"Hybrid-spheroids incorporating ECM like engineered fragmented fibers potentiate stem cell function by improved cell\/cell and cell\/ECM interactions","volume":"64","author":"Ahmad","year":"2017","journal-title":"Acta Biomater."},{"key":"10.1016\/j.jconrel.2026.114798_bb0260","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.4252\/wjsc.v12.i12.1455","article-title":"Effect of metformin on stem cells: molecular mechanism and clinical prospect","volume":"12","author":"Jiang","year":"2020","journal-title":"World J. Stem Cells"},{"key":"10.1016\/j.jconrel.2026.114798_bb0265","doi-asserted-by":"crossref","first-page":"54","DOI":"10.15171\/jrip.2019.11","article-title":"Metformin and its anti-inflammatory and anti-oxidative effects; new concepts","volume":"8","author":"Dehkordi","year":"2018","journal-title":"J. Renal Inj. Prev."},{"key":"10.1016\/j.jconrel.2026.114798_bb0270","doi-asserted-by":"crossref","first-page":"eabj2281","DOI":"10.1126\/sciadv.abj2281","article-title":"Hybrid SMART spheroids to enhance stem cell therapy for CNS injuries","volume":"7","author":"Rathnam","year":"2021","journal-title":"Sci. Adv."},{"key":"10.1016\/j.jconrel.2026.114798_bb0275","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41574-023-00833-4","article-title":"Metformin: update on mechanisms of action and repurposing potential","volume":"19","author":"Foretz","year":"2023","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0280","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2147\/VHRM.S391808","article-title":"Repurposing metformin for the treatment of atrial fibrillation: current insights","author":"Sarkar","year":"2024","journal-title":"Vasc. Health Risk Manag."},{"key":"10.1016\/j.jconrel.2026.114798_bb0285","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1021\/acsbiomaterials.0c00124","article-title":"Effects of targeted delivery of metformin and dental pulp stem cells on osteogenesis via demineralized dentin matrix under high glucose conditions","volume":"6","author":"Gao","year":"2020","journal-title":"ACS Biomater. Sci. Eng."},{"key":"10.1016\/j.jconrel.2026.114798_bb0290","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2021.120850","article-title":"Metformin facilitates mesenchymal stem cell-derived extracellular nanovesicles release and optimizes therapeutic efficacy in intervertebral disc degeneration","volume":"274","author":"Liao","year":"2021","journal-title":"Biomaterials"},{"key":"10.1016\/j.jconrel.2026.114798_bb0295","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13287-015-0072-7","article-title":"Lipopolysaccharide preconditioning of adipose-derived stem cells improves liver-regenerating activity of the secretome","volume":"6","author":"Lee","year":"2015","journal-title":"Stem Cell Res. Ther."},{"key":"10.1016\/j.jconrel.2026.114798_bb0300","first-page":"121","article-title":"Mesenchymal stromal\/stem cell spheroid-derived extracellular vesicles advance the therapeutic efficacy of 3D-printed vascularized artificial liver lobules in liver failure treatment","volume":"49","author":"Zhang","year":"2025","journal-title":"Bioact. Mater."},{"key":"10.1016\/j.jconrel.2026.114798_bb0305","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.5152\/eurasianjmed.2023.23364","article-title":"Experimental Sepsis models: advantages and limitations","volume":"55","author":"Ayd\u0131n","year":"2023","journal-title":"Eurasian J. Med."},{"key":"10.1016\/j.jconrel.2026.114798_bb0310","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1084\/jem.20180008","article-title":"Endothelial cell fitness dictates the source of regenerating liver vasculature","volume":"215","author":"Singhal","year":"2018","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.jconrel.2026.114798_bb0315","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.jpedsurg.2018.02.006","article-title":"Liver damage, proliferation, and progenitor cell markers in experimental necrotizing enterocolitis","volume":"53","author":"Miyake","year":"2018","journal-title":"J. Pediatr. Surg."},{"key":"10.1016\/j.jconrel.2026.114798_bb0320","doi-asserted-by":"crossref","first-page":"2309899","DOI":"10.1002\/advs.202309899","article-title":"3D printing of a vascularized mini-liver based on the size-dependent functional enhancements of cell spheroids for rescue of liver failure","volume":"11","author":"Zhang","year":"2024","journal-title":"Adv. Sci."},{"key":"10.1016\/j.jconrel.2026.114798_bb0325","doi-asserted-by":"crossref","first-page":"2402999","DOI":"10.1002\/adfm.202402999","article-title":"Ion-specific hydrogel microcarriers with biomimetic niches for Bioartifical liver system","volume":"34","author":"Lin","year":"2024","journal-title":"Adv. Funct. Mater."},{"key":"10.1016\/j.jconrel.2026.114798_bb0330","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/s41565-022-01137-w","article-title":"NAD (H)-loaded nanoparticles for efficient sepsis therapy via modulating immune and vascular homeostasis","volume":"17","author":"Ye","year":"2022","journal-title":"Nat. Nanotechnol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0335","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41392-025-02162-6","article-title":"Host FSTL1 defines the impact of stem cell therapy on liver fibrosis by potentiating the early recruitment of inflammatory macrophages","volume":"10","author":"Zheng","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.jconrel.2026.114798_bb0340","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.scib.2024.02.030","article-title":"Biomimetic hepatic lobules from three-dimensional imprinted cell sheets","volume":"69","author":"Wang","year":"2024","journal-title":"Sci. Bull."},{"key":"10.1016\/j.jconrel.2026.114798_bb0345","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.1038\/s41467-024-50341-w","article-title":"Sphinganine recruits TLR4 adaptors in macrophages and promotes inflammation in murine models of sepsis and melanoma","volume":"15","author":"Hering","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jconrel.2026.114798_bb0350","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1073\/pnas.2434651100","article-title":"Reversing established sepsis with antagonists of endogenous high-mobility group box 1","volume":"101","author":"Yang","year":"2004","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.jconrel.2026.114798_bb0355","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1055\/a-1322-7478","article-title":"Short-term effects of metformin on cardiac and peripheral blood cells following cecal ligation and puncture-induced sepsis","volume":"71","author":"Didari","year":"2021","journal-title":"Drug Res."},{"key":"10.1016\/j.jconrel.2026.114798_bb0360","doi-asserted-by":"crossref","first-page":"1209438","DOI":"10.3389\/fimmu.2023.1209438","article-title":"The role of macrophages polarization in sepsis-induced acute lung injury","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0365","doi-asserted-by":"crossref","first-page":"1238972","DOI":"10.3389\/fimmu.2023.1238972","article-title":"Advances in mesenchymal stem cells regulating macrophage polarization and treatment of sepsis-induced liver injury","volume":"14","author":"Chen","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0370","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2021.107823","article-title":"Anti-inflammatory and M2 macrophage polarization-promoting effect of mesenchymal stem cell-derived exosomes","volume":"97","author":"Arabpour","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0375","doi-asserted-by":"crossref","first-page":"669","DOI":"10.14218\/JCTH.2021.00127","article-title":"Transplantation of mesenchymal stem cells attenuates acute liver failure in mice via an interleukin-4-dependent switch to the M2 macrophage anti-inflammatory phenotype","volume":"10","author":"Wang","year":"2022","journal-title":"J. Clin. Transl. Hepatol."},{"key":"10.1016\/j.jconrel.2026.114798_bb0380","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00418-018-1731-4","article-title":"Bone marrow-derived mesenchymal stem cells ameliorate liver injury in a rat model of sepsis by activating Nrf2 signaling","volume":"151","author":"Selim","year":"2019","journal-title":"Histochem. Cell Biol."},{"key":"10.1016\/j.jconrel.2026.114798_bib386","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1186\/1756-0500-7-233","article-title":"A robust scoring system to evaluate sepsis severity in an animal model","volume":"7","author":"Shrum","year":"2014","journal-title":"BMC Res. Notes."}],"container-title":["Journal of Controlled Release"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365926002002?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365926002002?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:05:22Z","timestamp":1781715922000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168365926002002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":77,"alternative-id":["S0168365926002002"],"URL":"https:\/\/doi.org\/10.1016\/j.jconrel.2026.114798","relation":{},"ISSN":["0168-3659"],"issn-type":[{"value":"0168-3659","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Bioengineered hybrid spheroids integrating mesenchymal stem cells and metformin-loaded microspheres for the treatment of sepsis-induced liver injury","name":"articletitle","label":"Article Title"},{"value":"Journal of Controlled Release","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jconrel.2026.114798","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"114798"}}