Synthesis and characterization of SPUU–PEO–heparin graft copolymers

Abstract

A new synthetic approach for the preparation of segmented polyurethaneurea (SPUU)–PEO–Heparin graft copolymers (B–PEO–Hep) has been developed. The procedure involved the coupling of hexamethylene diisocyanate (HMDI) to soluble Biomer® (B) through an allophanate/biuret reaction. The free isocyanate (NCO) groups attached to Biomer® were then coupled to PEO terminal hydroxyl groups to form PEO grafted Biomer® (B–PEO). B–PEO free hydroxy groups were modified with HMDI to introduce terminal isocyanate groups. The NCO functionalized B–PEO was then coupled to heparin (Hep) functional groups (OH, NH2) producing B–PEO–Hep graft copolymer. Synthetic intermediates were confirmed by FTIR, NCO group determination, and toluidine blue heparin assay. Physical characterization techniques, such as contact angle measurements, water swelling, light scattering measurements, and DSC thermal analysis, detailed properties of the graft copolymer containing covalently bound heparin. This new heparinized copolymer can be applied as a coating on other existing blood contacting surfaces without changing bulk properties. The heparin bioactivity observed attests to the usefulness of this new procedure as a coating to improve the blood compatibility of blood‐contacting surfaces.

Fabrication of endothelial cell-specific polyurethane surfaces co-immobilized with GRGDS and YIGSR peptides

“…As the results, blood-contacting synthetic biomaterials have been found out to generally induce thrombus formation, which is initiated by absorbed plasma proteins on the surfaces, followed by platelet adhesion and activation along coagulation pathways. 7,8 Based upon these phenomena at the interface, various approaches in terms of blood compatibility have been readily attempted and the progresses for modifying surface properties of PU include (1) chemical modification by the grafting of hydrophilic components, like poly(ethylene glycol) (PEG) or biomembrane structure; 4,[9][10][11] (2) surface modification by incorporating bioactive agents such as fibrolytic enzymes (t-plasminogen activator, urokinase), various prostaglandins (PGE 1 ), and potent anticoagulant (heparin and hirudin), through either physical or chemical coupling 9,12-15 and (3) biological modification using protein or endothelial cells (ECs) seeding. 16,17 Among them, the most promising one can be a biomimetic approach that takes advantage of the highly thromboresistance of EC layer, which presents as the inner surface of the natural vessel wall that constitutionally perform a regulatory role in hemostasis.…”

“…10,11,26 Other results demonstrate that PEG can provide more opportunities for binding with biological matters such as proteins or cells due to the high mobility on water interface if it can act as the spacer arm with a biofunctionality. 9,27,28 In this study, PU surface was firstly modified with PEG as a spacer for an effective EC activity, and then two kinds of ECs-adhesive peptides (GRGDS and YIGSR) were chemically immobilized. With surface characterizations of the modified PU, EC activities on these surfaces were investigated in vitro.…”

Design of Nonthrombogenic Polymer Surfaces for Blood-Contacting Medical Devices

“…PU and PU-(PEO-4.000) demonstrated a thick protein layer (table 5), where as PU-(PEO-4,QOO)- HEP displayed a monolayer protein thick ness. The distribution of specific proteins on the various surfaces, as determined by trans mission electron microscopy revealed that PU-(PEO-4,000)-HEP showed a protein pat tern relatively enriched with albumin and IgG, but less fibrinogen, while PU and PU-(PEO-4.000) showed a multilayered pattern with relatively high concentrations of fibrino gen. but less albumin [7], The overall patency of the vascular graft surfaces is summarized in tableó, demon strating that PEO-heparin surfaces showed significant improvements over other surfaces [24], These results suggest that the surface properties of a polymer may control the pro tein adsorption pattern, and that the composi tion of adsorbed protein is essential to pro vide long-term in vivo blood compatibility.…”

“…Both tri block-and pentablock-coated PU demon strated significant improvement in blood compatibility compared to native PU surfaces [22,23]. We recently extended this research to synthesize PU polymers grafted with PEO and heparin (PU-PEO-HEP) [24], This wellcharacterized heparinized polymer was coated onto a PU surface and evaluated for in vitro and in vivo blood compatibility. As shown in figure 9, coated graft copolymers will reorient hydrophilic PEO and heparin when in contact with blood to reduce surfaceinduced thrombosis.…”

One-Step Surface Modification of Poly(lactide-co-glycolide) Microparticles with Heparin

“…Heparin binds with toluidine blue and precipitates out from the aqueous solution. In previous studies, heparin-toluidine complexes were removed by extraction with hexane and the decrease in the absorbance of toluidine solution was used to correlate with heparin concentration (27,28). Here, we found that the hexane/water interface is not sufficient to completely remove the complexes.…”