{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T07:15:06Z","timestamp":1763018106484,"version":"3.40.5"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,10,13]],"date-time":"2019-10-13T00:00:00Z","timestamp":1570924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900574","81800562","81770618"],"award-info":[{"award-number":["81900574","81800562","81770618"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The challenge of using bioengineered liver lies in sustaining the quantity of high\u2010quality hepatocytes and the vasculature for blood perfusion. We characterized the heparinization of a porcine decellularized liver scaffold (DLS) as a carrier to support hepatocyte angiogenesis, thereby developing functional and vascularized hepatic tissue useful to treat liver injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>The porcine DLS was obtained by the removal of cellular components and then subjected to heparinization by the end\u2010point attachment technique. The heparinized DLSs were recellularized with rat hepatocyte spheroids to construct engineered hepatic tissue. The hepatic tissue was heterotopically implanted in the omentum majus of a rat model with liver injury induced by carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hepatocyte spheroids in the heparinized DLS remained viable for at least 10\u00a0weeks in vivo. The entire scaffold was populated with hepatocytes and arranged well. The volume of the heparinized DLS group was expanded over 400\u2010fold. Liver\u2010specific functions such as albumin synthesis, glycogen storage and cytochrome P 3A4 activity were highly expressed in the hepatic tissue. In addition, endothelial cells were recruited, as shown by CD31 staining, and new blood vessels formed, as visualized by fluorescein isothiocyanate\u2010labelled dextran intravital confocal microscopy. The heparinized bioengineered hepatic tissue alleviated CCl<jats:sub>4<\/jats:sub>\u2010induced liver injury by regulating the deposition and degradation of the extracellular matrix.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Primary hepatocyte spheroids survived for an extended time on the heparinized DLS and expanded to generate vascularized and functional bioengineered hepatic tissue that can alleviate liver injury in rats.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14267","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T06:27:21Z","timestamp":1569911241000},"page":"712-726","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Heterotopic vascularization and functionalization of implantable bio engineered hepatic tissue alleviates liver injury in 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