Title : Heparinized bioengineered liver scaffolds as a strategy to enhance vascularization and mitigate liver fibrosis in mice model
Abstract:
End-stage liver disease (ESLD), resulting from advanced fibrosis and cirrhosis, often requires liver transplantation, but the shortage of suitable donors remains a critical limitation. Bioengineered livers offer a promising alternative; however, thrombosis due to the absence of a functional endothelial lining in decellularized liver scaffolds (DLS) limits their application. In this study, we hypothesized that heparin immobilized decellularized liver scaffolds would promote endothelialization and angiogenesis of scaffolds, enhancing their therapeutic potential in fibrotic liver models.
Heparin was covalently immobilized onto rat decellularized liver scaffolds using the end-point attachment technique. These heparinized scaffolds (HEP-DLS) were recellularized with human umbilical vein endothelial cells (HUVECs) via the portal vein and maintained in a perfusion bioreactor for 7 days. Histological analysis confirmed that heparinized scaffolds (HEP-DLS) exhibited significantly improved endothelial cell adhesion, proliferation, and vascular coverage. To assess angiogenic potential in vivo, the constructs were implanted into the omentum of mice for 21 days, resulting in significantly increased neovascularization in the HEP-DLS group.
Furthermore, implantation of heparinized recellularized liver tissue into the interlobular space of a thioacetamide-induced liver fibrosis mouse model resulted in marked reductions in serum ALT and AST levels, along with histological evidence of tissue regeneration and extracellular matrix remodeling.
Our findings suggest that heparin-functionalized scaffolds promote re-endothelialization and angiogenesis, supporting the development of functional bioengineered liver tissue and offering a potential therapeutic strategy to alleviate liver fibrosis.
Keywords: liver; heparin; re-endothelialization; angiogenesis; fibrosis
