In vivo nonthrombogenicity of heparin immobilized polymer surfaces.
The authors developed two different methods to immobilize heparin on polymer surfaces. One method involves in situ heparin immobilization on a segmented polyurethane urea (Biomer) surface via hydrophilic poly(ethylene oxide) (PEO, Mn = 4,000) spacers. The other method uses PEO/poly(dimethylsiloxane) (PDMS) block co-polymer and heparin covalently linked in a block co-polymer system (PEO-PDMS-Hep). These surfaces have demonstrated high heparin bioactivity in vitro and excellent blood compatibility in in vitro-ex vivo experiments. This report evaluates the long-term in vivo blood compatibility of these heparin immobilized surfaces. Vascular grafts (6 mm ID, 7 cm in length) were fabricated with Biomer, and heparin was immobilized in situ with PEO spacers (B-PEO4K) and coated on their luminal surfaces with PEO-PDMS-Hep. Biomer and PEO (Mn = 4,000) grafted Biomer (B-PEO4K) were used as controls. The grafts were implanted in the abdominal aorta of dogs and retrieved at 3 months or when graft occlusion was suspected. Retrieved grafts were evaluated with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). TEM measured the thickness of the adsorbed protein layer on the surface and the protein distribution (albumin, fibrinogen, and IgG) visualized by an immunogold method. All heparin immobilized grafts were patent at 3 months, whereas Biomer and B-PEO4K grafts occluded within 1 month. SEM pictures of heparin immobilized surfaces after 3 months demonstrated minimal platelet adhesion and activation without detectable fibrin formation. Heparin immobilized surfaces showed a thin protein layer (300-600 A) even after 3 months, with high concentrations of albumin and IgG and less fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)
Nojiri
C
C
Department of Pharmaceutics/CCCD, University of Utah, Salt Lake City.
Park
K D
KD
Grainger
D W
DW
Jacobs
H A
HA
Okano
T
T
Koyanagi
H
H
Kim
S W
SW
D000818:Animals; D001672:Biocompatible Materials; D001807:Blood Vessel Prosthesis; D004285:Dogs; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006493:Heparin; D008854:Microscopy, Electron; D011140:Polyurethanes; D011474:Prosthesis Design; D013499:Surface Properties
D001672:Biocompatible Materials; D011140:Polyurethanes; C031892:biomer; D006493:Heparin