title: Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues.
abstract: Thrombosis within small-diameter vascular grafts limits the development of bioartificial, engineered vascular conduits, especially those derived from extracellular matrix (ECM). Here we describe an easy-to-implement strategy to chemically modify vascular ECM by covalently linking a collagen binding peptide (CBP) to heparin to form a heparin derivative (CBP-heparin) that selectively binds a subset of collagens. Modification of ECM with CBP-heparin leads to increased deposition of functional heparin (by ∼7.2-fold measured by glycosaminoglycan composition) and a corresponding reduction in platelet binding (>70%) and whole blood clotting (>80%) onto the ECM. Furthermore, addition of CBP-heparin to the ECM stabilizes long-term endothelial cell attachment to the lumen of ECM-derived vascular conduits, potentially through recruitment of heparin-binding growth factors that ultimately improve the durability of endothelialization in vitro. Overall, our findings provide a simple yet effective method to increase deposition of functional heparin on the surface of ECM-based vascular grafts and thereby minimize thrombogenicity of decellularized tissue, overcoming a significant challenge in tissue engineering of bioartificial vessels and vascularized organs.
authors.affiliation: Department of Surgery, Feinberg School of Medicine, Northwestern University , Chicago, Illinois 60611, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.forename: Rachel
authors.initials: R
authors.lastname: Suen
authors.affiliation: Department of Surgery, Feinberg School of Medicine, Northwestern University , Chicago, Illinois 60611, United States.|Department of Surgery, Jesse Brown VA Medical Center , Chicago, Illinois 60612, United States.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Wertheim
authors.affiliation: Department of Surgery, Feinberg School of Medicine, Northwestern University , Chicago, Illinois 60611, United States.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Ameer
mesh_terms: D000818:Animals; D020099:Coated Materials, Biocompatible; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006493:Heparin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D010973:Platelet Adhesiveness; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D020099:Coated Materials, Biocompatible; D010446:Peptide Fragments; D006493:Heparin; D003094:Collagen