Blood compatibility of PEO grafted polyurethane and HEMA/styrene block copolymer surfaces.
HEMA/styrene (HEMA/STY) block copolymers and poly(ethylene oxide) 4,000 M.W. (PEO4K) grafted Biomer (B-PEO4K) surfaces have been synthesized, characterized, and evaluated as blood-contacting materials. These surfaces have demonstrated improved blood compatibility, compared to Biomer, in in vitro and ex vivo experiments. Biomer vascular grafts (6 mm I.D. 7 cm in length) were fabricated by a dip coating process. The luminal surface was modified either with PEO grafting, HEMA/STY coating, or Biomer coating (control). These surface-modified grafts were implanted in the abdominal aortas of dogs and evaluated for graft patency and protein adsorption. Surface protein layer thickness was measured by transmission electron microscopy (TEM). B-PEO4K and Biomer showed thick multilayers of adsorbed proteins (1000-2000 A) after 3 weeks to 1 month implantation. In contrast, HEMA/STY only showed a monolayer protein thickness (less than 200 A), even after 3 months. Visualization of adsorbed plasma proteins (albumin, IgG, and fibrinogen) was performed with scanning electron microscopy (SEM)/TEM using an immunogold double antibody technique. The pattern of protein distribution showed high concentrations of fibrinogen and IgG, and less albumin adsorbed onto Biomer and B-PEO4K. In contrast, HEMA/STY showed a patchy protein distribution pattern with high concentrations of albumin and IgG, and relatively less fibrinogen. Adsorbed monolayer patterns showed improved compatibility over multilayered proteins. The Biomer and B-PEO4K grafts occluded within 1 month, while HEMA/STY grafts were patent for over 3 months. The thin and stable adsorbed protein layer on HEMA/STY surfaces may be associated with the microdomain structures of the surface, and will play an important role in long-term in vivo blood compatibility. This manuscript will evaluate the long-term in vivo performance of these polymers, analyze the extent of protein adsorption onto the surfaces, and correlate protein layer thickness to the thrombogenicity of the polymer surfaces.
Department of Pharmaceutics/Center for Controlled Chemical Delivery, University of Utah, Salt Lake City 84108.
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C
Nojiri
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Okano
H A
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Jacobs
K D
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Park
S F
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Mohammad
D B
DB
Olsen
S W
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Kim
D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials; D001777:Blood Coagulation; D001798:Blood Proteins / Q000378:metabolism; D001807:Blood Vessel Prosthesis; D004285:Dogs; D008422:Materials Testing; D008689:Methacrylates; D008854:Microscopy, Electron; D011140:Polyurethanes; D013499:Surface Properties
D001672:Biocompatible Materials; D001798:Blood Proteins; D008689:Methacrylates; D011140:Polyurethanes; C005044:hydroxyethyl methacrylate