Adsorption of plasminogen from human plasma to lysine-containing surfaces

The objective of this work is to develop a blood contacting surface that possesses both resistance to nonspecific protein adsorption and clot lysing properties. Chemical modification of a polyurethane (PU) surface with poly(ethylene glycol) (PEG); and lysine was used to create a plasminogen-binding potentially fibrinolytic surface. The preparation involves modification of the PU surface with dihydroxy PEG, reaction of the unreacted distal OH with N,N'-disuccinimidyl carbonate (DSC) to produce a PU-PEG-NHS surface, followed by conjugation of epsilon-amino-protected lysine (H-Lys(t-BOC)-OH) by reaction of the alpha-amino group with the NHS and deprotection. The result is a lysine-derivatized surface in which the epsilon-amino groups of the lysine are free to participate in binding plasminogen and tissue plasminogen activator (t-PA). Surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. Protein adsorption experiments showed that nonspecific protein adsorption was greatly reduced on these surfaces and that they adsorbed significant quantities of plasminogen from plasma. After incubation with plasma and treatment with t-PA the surfaces were able to dissolve nascent plasma clots formed around them.

Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Surfaces having dual fibrinolytic and protein resistant properties by immobilization of lysine on polyurethane through a PEG spacer

Chen

Zhang

et al. 2008

“…Recently,4, 5 a thromboresistant material obtained by photochemical attachment polyacrylamide bearing α‐aminocoupled lysine to polyurethane has been reported. A material based on dextran with covalently attached dipeptide l ‐cysteinyl‐ l ‐lysine was also prepared 6…”

Section: Introductionmentioning

confidence: 99%

Polyelectrolyte thromboresistant affinity coatings for modification of devices contacting blood

Самойлова¹,

Krayukhina²,

Novikova³

et al. 2007

The modification of hydrophobic polyethylene/polystyrene surfaces of medical devices with bilayer/multilayer coatings (BCs/MCs) based on polyelectrolyte complexes (PEC) of modified poly(N-vinylpyrrolidone-co-maleic acid) copolymer (VPMA) with chitosan, amphiphilic chitosan, or albumin was studied. The VPMA contained l-Lysine as affinity ligand for plasminogen attached through alpha-amino group. The surface properties and chemical composition of the surfaces investigated were analyzed, using sessile-drop water contact angle measurements, attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). The specific adsorption of plasminogen (precursor of fibrinolytic enzyme plasmin) from its solutions and from human blood plasma on the modified surfaces was investigated. It was established that polyelectrolyte MCs are more efficient than single-layer BCs and the affine polymer coatings without interlayer. A thrombogenicity decrease for the materials modified with BCs and MCs was shown in in vitro and ex vivo trials.

Interactions of fibrinolytic system proteins with lysine‐containing surfaces

McClung

Clapper

Anderson

et al. 2003

Studies on the interactions of tissue plasminogen activator (tPA) and plasminogen with polyurethane surfaces containing epsilon-lysine moieties (epsilon-amino group free) are reported. These surfaces are considered to have the potential to dissolve nascent clots that may be formed on them. For adsorption from both single protein solutions and plasma, the surfaces were found to have a high capacity for tPA as well as plasminogen. A significant fraction of preadsorbed tPA was displaced from the epsilon-lysine surfaces upon contact with plasma. These surfaces, when preadsorbed with tPA and then incubated with plasma, were able to dissolve incipient clots formed around them. However, the clot-dissolving capacity diminished as the time of plasma incubation increased, presumably due to loss of tPA. It was also shown that in plasma, preadsorbed tPA is displaced from these surfaces largely by plasminogen, which thus appears to have a greater binding affinity than tPA for the epsilon-lysine moieties. Finally, it was found that in plasma, the epsilon-lysine surfaces interact with plasminogen in a dynamic manner, and that about 70% of the bound plasminogen is exchanging continuously with plasminogen in the plasma.