Heparin Immobilization Enhances Hemocompatibility, Re-Endothelization, and Angiogenesis of Decellularized Liver Scaffolds.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Heparin*/pharmacology ; Heparin*/chemistry ; Tissue Scaffolds*/chemistry ; Liver*/metabolism ; Neovascularization, Physiologic*/drug effects ; Cell Adhesion*/drug effects ; Endothelial Cells*/drug effects ; Endothelial Cells*/metabolism ; Endothelial Cells*/cytology; Animals ; Rats ; Mice ; Humans ; Platelet Adhesiveness/drug effects ; Tissue Engineering/methods ; Male ; Cell Movement/drug effects ; Thrombosis/etiology ; Angiogenesis
    • Abstract:
      Bioengineered livers are currently an acceptable alternative to orthotopic liver transplants to overcome the scarcity of donors. However, the challenge of using a bioengineered liver is the lack of an intact endothelial layer in the vascular network leading to thrombosis. Heparin-modified surfaces have been demonstrated to decrease thrombogenicity in earlier research. However, in our study, we aimed to apply heparin immobilization to enhance the hemocompatibility, endothelial cell (EC) adhesion, and angiogenesis of rat decellularized liver scaffolds (DLS). Heparin was immobilized on the DLS by the end-point attachment technique. The scaffold's hemocompatibility was assessed using ex vivo blood perfusion and platelet adhesion studies. The heparinized scaffold (HEP-DLS) showed a significantly reduced thrombogenicity and platelet aggregation. HEP-DLS was recellularized with EA.hy926 cells via the portal vein and maintained in the bioreactor for 7 days, showing increased EC adhesion and coverage within the blood vessels. The Resazurin reduction assay confirmed the presence of actively proliferating cells in the HEP-DLS. The scaffolds were implanted subcutaneously into the dorsum of mice for 21 days to evaluate cell migration and angiogenesis. The results showed significant increases in the number of blood vessels in the HEP-DLS group. Our results demonstrated that heparin immobilization reduces thrombosis, promotes re-endothelialization, and enhances angiogenesis in DLS. The research provides insight into the potential use of heparin in the formation of a functioning vasculature.
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    • Grant Information:
      22A0101L1-11 Korean fund for Regenerative Medicine (KFRM) (the Ministry of Science and ICT, the Ministry of Health & Welfare)
    • Contributed Indexing:
      Keywords: angiogenesis; hemocompatibility; heparin; liver; re-endothelialization
    • Accession Number:
      9005-49-6 (Heparin)
    • Publication Date:
      Date Created: 20241127 Date Completed: 20241127 Latest Revision: 20241130
    • Publication Date:
      20241202
    • Accession Number:
      PMC11595110
    • Accession Number:
      10.3390/ijms252212132
    • Accession Number:
      39596200