title: Heparin-modified small-diameter nanofibrous vascular grafts.
abstract: Due to high incidence of vascular bypass procedures, an unmet need for suitable vessel replacements exists, especially for small-diameter   vascular grafts. Here we produced 1-mm diameter vascular grafts with nanofibrous structure via electrospinning, and successfully modified the nanofibers by the conjugation of heparin using di-amino-poly(ethylene glycol) (PEG) as a linker. Antithrombogenic activity of these heparin-modified scaffolds was confirmed in vitro. After 1 month implantation using a rat common carotid artery bypass model, heparin-modified grafts exhibited 85.7% patency, versus 57.1% patency of PEGylated grafts and 42.9% patency of untreated grafts. Post-explant analysis of patent grafts showed complete endothelialization of the lumen and neovascularization around the graft. Smooth muscle cells were found in the surrounding neo-tissue. In addition, greater cell infiltration was observed in heparin-modified grafts. These findings suggest heparin modification may play multiple roles in the function and remodeling of nanofibrous vascular grafts, by preventing thrombosis and maintaining patency, and by promoting cell infiltration into the three-dimensional nanofibrous structure for remodeling.
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720USA.
authors.forename: Randall Raphael R
authors.initials: RR
authors.lastname: Janairo
authors.forename: Jeffrey J D
authors.initials: JJ
authors.lastname: Henry
authors.forename: Benjamin Li-Ping
authors.initials: BL
authors.lastname: Lee
authors.forename: Craig K
authors.initials: CK
authors.lastname: Hashi
authors.forename: Nikita
authors.initials: N
authors.lastname: Derugin
authors.forename: Randall
authors.initials: R
authors.lastname: Lee
authors.forename: Song
authors.initials: S
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D001807:Blood Vessel Prosthesis; D004730:Endothelium, Vascular / Q000187:drug effects; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006651:Histocytochemistry; D057139:Nanofibers / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010316:Particle Size; D011091:Polyesters; D051381:Rats; D017207:Rats, Sprague-Dawley; D058017:Vascular Grafting / Q000295:instrumentation*; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D000925:Anticoagulants; D001672:Biocompatible Materials; D011091:Polyesters; C033616:poly(lactide); D006493:Heparin