title: Development of thrombus-resistant and cell compatible crimped polyethylene terephthalate cardiovascular grafts using surface co-immobilized heparin and collagen.
abstract: Short-term patency of polyethylene terephthalate (PET) cardiovascular grafts is determined mainly by the inherent thrombogenicity and improper endothelialization following grafts implantation. The aim of the present study was to immobilize heparin to develop thrombus resistant grafts. Additionally, collagen was co-immobilized to enhance the host cell compatibility. The synthetic woven and knitted forms of crimped PET grafts were surface modified by Denier reduction to produce functional carboxyl groups. The produced groups were used as anchor sites for covalent immobilization of heparin or co-immobilization of heparin/collagen by the end-point method. The modified surface was characterized using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The biological activity of immobilized molecules was investigated in vitro using direct blood coagulation test, and "platelet deposition under flow condition. Furthermore, the biocompatibility of modified grafts with host cells was assessed using L929 cell as model. All modified grafts showed significant resistance against fibrin and clot formation. The number of deposited platelets on heparin-immobilized woven and knitted grafts obviously decreased by 3 fold and 2.8 fold per unit surface area respectively, while the heparin/collagen co-immobilized grafts showed only a decrease by 1.7 and 1.8 fold compared to unmodified PET. Heparin-immobilized grafts reported no significant effect on L929 cells adhesion and growth (P>0.05), conversely, collagen co-immobilization considerably increased cell adhesion almost ~1.3 fold and 2 fold per unit surface area for woven and knitted grafts respectively. Our results emphasize that immobilization of heparin minimized the inherent thrombogenicity of the PET grafts. The simultaneous co-immobilization of collagen supported host cell adhesion and growth required for the grafts biocompatibility.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg, Germany. Electronic address: almeslmanib@yahoo.com.
authors.forename: Bassam
authors.initials: B
authors.lastname: Al Meslmani
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg, Germany; Department of Pharmaceutics and Industrial Pharmacy, Helwan University, Ain Helwan, 11795 Cairo, Egypt. Electronic address: mahmoudg@staff.uni-marburg.de.
authors.forename: Gihan
authors.initials: G
authors.lastname: Mahmoud
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg, Germany. Electronic address: strehlo4@staff.uni-marburg.de.
authors.forename: Boris
authors.initials: B
authors.lastname: Strehlow
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg, Germany. Electronic address: mohr@staff.uni-marburg.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Mohr
authors.affiliation: Institute of Physical Chemistry, Justus-Liebig-University, Heinrich-Buff-Ring 58, 35392 Giessen, Germany. Electronic address: Thomas.leichtweiss@phys.chemie.uni-giessen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Leichtweiß
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Marburg University, Ketzerbach 63, 35037 Marburg, Germany. Electronic address: ubakowsky@aol.com.
authors.forename: Udo
authors.initials: U
authors.lastname: Bakowsky
mesh_terms: D020099:Coated Materials, Biocompatible; D003094:Collagen / Q000008:administration & dosage*; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D011093:Polyethylene Terephthalates; D017550:Spectroscopy, Fourier Transform Infrared; D013927:Thrombosis / Q000517:prevention & control*; D058017:Vascular Grafting
chemical_list: D020099:Coated Materials, Biocompatible; D011093:Polyethylene Terephthalates; D006493:Heparin; D003094:Collagen
keywords: Blood compatibility; Collagen; Crimped cardiovascular PET grafts; Heparin; Surface immobilization; Thrombus