title: Click-coated, heparinized, decellularized vascular grafts.
abstract: A novel method enabling the engineering of a dense and appropriately oriented heparin-containing layer on decellularized aortas has been developed. Amino groups of decellularized aortas were first modified to azido groups using 3-azidobenzoic acid. Azide-clickable dendrons were attached onto the azido groups through "alkyne-azide" click chemistry, affording a tenfold amplification of adhesions sites. Dendron end groups were finally decorated with end-on modified heparin chains. Heparin chains were oriented like heparan sulfate groups on native endothelial cells surface. X-ray photoelectron spectroscopy, nuclear magnetic resonance imaging, mass spectrometry and Fourier transform infrared FTIR spectroscopy were used to characterize the synthesis steps, building the final heparin layered coatings. The continuity of the heparin coating was verified using fluorescent microscopy and histological analysis. The efficacy of heparin linkage was demonstrated with factor Xa anti-thrombogenic assay and platelet adhesion studies. The results suggest that oriented heparin immobilization to decellularized aortas may improve the in vivo blood compatibility of decellularized aortas and vessels.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT 06510, USA.
authors.forename: Sashka
authors.initials: S
authors.lastname: Dimitrievska
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Weyers
authors.affiliation: Department of Anesthesiology and Biomedical Engineering, Yale University, New Haven, CT 06510, USA.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Balestrini
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT 06510, USA.
authors.forename: Tylee
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology and Biomedical Engineering, Yale University, New Haven, CT 06510, USA.
authors.forename: Sumati
authors.initials: S
authors.lastname: Sundaram
authors.affiliation: Department of Anesthesiology and Biomedical Engineering, Yale University, New Haven, CT 06510, USA.
authors.forename: Go
authors.initials: G
authors.lastname: Hatachi
authors.affiliation: Departments of Chemistry and Pharmacology, Yale University, New Haven, CT 06510, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Spiegel
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT 06510, USA.
authors.forename: Themis R
authors.initials: TR
authors.lastname: Kyriakides
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Miao
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
authors.forename: Guoyun
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Biomedical Engineering, Yale University, New Haven, CT 06510, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Niklason
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA. Electronic address: linhar@rpi.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D000818:Animals; D001011:Aorta; D001807:Blood Vessel Prosthesis; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008422:Materials Testing; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D013927:Thrombosis / Q000378:metabolism / Q000517:prevention & control
chemical_list: D020099:Coated Materials, Biocompatible; D006493:Heparin
keywords: Heparin; Small-diameter vascular grafts; Thrombogenicity; “Click” bioorthogonal coating