Enhanced vascularization in a microporous polyurethane graft impregnated with basic fibroblast growth factor and heparin.
Rapid and controlled neoarterial regeneration via perianastomotic as well as transmural tissue ingrowth is critical to patency of implanted small-caliber artificial vascular grafts. Microporous polyurethane (PU) grafts (inner diameter, 1.5 mm; wall thickness, 100 microns; length, 20 mm; pore size, 100 microns), fabricated using an excimer laser ablation technique, were coated with a mixed solution of photoreactive gelatin, basic fibroblast factor (bFGF), and heparin, and were photocured by ultraviolet irradiation. Control grafts were treated with only photoreactive gelatin. An in vitro study showed that coimmobilization of bFGF and heparin (bFGF/heparin) in a crosslinked gelatin gel significantly enhances proliferation of endothelial cells. The bFGF/heparin-impregnated grafts (n = 6) and nonimpregnated (control) grafts (n = 9) were implanted in aortas of rats for 4 weeks. All the implanted grafts were patent, but there was a marked difference in the extent of neoarterial regeneration between the two groups. Irrespective of group, endothelialization proceeded from anastomotic sites and little occurrence of transmural capillary ingrowth was observed. The extent of endothelialization was much greater for bFGF/heparin-immobilized grafts than that for controls. In subendothelial tissues for the impregnated group, a significantly profound peripheral transmural tissue ingrowth including recruits of smooth muscle cells and fibroblasts from adjacent native tissue was observed near anastomotic sites; subendothelial tissue regeneration was noticed at the midportions of the grafts. However, only a fibrin layer was formed on control grafts. Thus, coimmobilization of bFGF and heparin significantly accelerated neoarterial regeneration via both perianastomotic and transmural tissue ingrowth. The former was more extensive than the latter.
Doi
K
K
Department of Bioengineering, National Cardiovascular Center Research Institute, Osaka, Japan.
Matsuda
T
T
D000818:Animals; D001672:Biocompatible Materials; D001807:Blood Vessel Prosthesis; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D005780:Gelatin; D006493:Heparin / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008297:Male; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic; D011140:Polyurethanes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D013997:Time Factors
D001672:Biocompatible Materials; D011140:Polyurethanes; D016222:Fibroblast Growth Factor 2; D005780:Gelatin; D006493:Heparin