Heparinization blood compatibility

PDMS-co-PS has been proposed to have the antithrombogenicity. PDMS-PEO-heparin has been synthesized to achieve better blood compatibility. Silicone-PC copolymers are always used as blood oxygenation, dialysis, and microelectrode membranes. 

We have recently turned our attention to cellulose-heparin, blood-compatible, nanoporous composite membranes for use in kidney dialysis (Murugesan et al., 2006a, b). Advanced kidney dialysis system contains heparin covalently bound to the surface of biomaterials to reduce clotting effects. Our new approach relies instead on composite materials. Unfortunately, no technology has been available to... 

Polyelectrolytes have been widely investigated as components of biocompatible materials. Biomaterials come into contact with blood when used as components in invasive instruments, implant devices, extracorporeal devices in contact with blood flow, implanted parts of hard structural elements, implanted parts of organs, implanted soft tissue substitutes and drug delivery devices. Approaches to the development of blood compatible materials include surface modification to give blood compatibility, polyelectrolyte-based systems which adsorb and/or release heparin as well as polyelectrolytes which mimic the biological activity of heparin. 

Ikada and coworkers also studied the blood compatibility and protein denaturation properties of heparin covalently and ionically bound onto polymer surfaces [513], Both types of bound heparin gave deactivation of the coagulation process. Clotting deactivation was attributed to a heparin/ antithrombin III complex by covalently bound heparin which gave adsorbed protein denaturation and platelet deformation as compared with lack of these features with ionically bound heparin. 

Problems of desorption and loss of activity encountered with natural heparin have led numerous workers to explore synthetic heparin-like polymers or heparinoids, as reviewed by Gebelein and Murphy [475, 514, 515]. The blood compatibility of 5% blended polyelectrolyte/polyfvinly alcohol) membranes was studied by Aleyamma and Sharma [516,517]. The membranes were modified with synthetic heparinoid polyelectrolytes, and surface properties (platelet adhesion, water contact angle, protein adsorption) and bulk properties such as permeability and mechanical characteristics were evaluated. The blended membrane had a lower tendency to adhere platelets than standard cellulose membranes and were useful as dialysis grade materials. 

Chitin and chitosan derivatives have also been studied as blood compatible materials both in vivo and in vitro [520], Anticoagulant activity was greatest with O sulfated N acetyl chitosan, followed by N,0 sulfated chitosan, heparin, and finally sulfated N acetyl chitosan. The lipolytic activity was greatest for N,0 sulfated chitosan followed by heparin. The generally poor performance of chitosan was attributed to polyelectrolyte complexes with free amino groups present on the membrane surface. The O sulfate or acidic group at the 6 position in the hexosamine moiety was identified as the main active site for anticoagulant activity. 

S.W. Kim et al. [35] examined blood compatibility of heparin-conjugated SPUU-PEO samples, which were prepared by introducing PEO (MW = 1000, 3350 and 7500, respectively) into Biomer, followed by conjugation of heparin. The surfaces of B-PEO 3.4 K and B-PEO 7.5 K were found to suppress mark-... 

Blood-compatible polymer materials are required to inhibit both platelet adhesion and coagulation just as the endothelial on the polymer surface. It is known that there are many investigations in the design and the synthesis of socalled antithrombogenic materials. The immobilization of biologically active substances such as heparin [74, 75], urokinase [76], and prostaglandins [77-81] is one of the practical approaches. 

While a biologically active surface performs well based on the specific biological reaction, it is a highly perturbable surface tailored for the specific reaction that could, in principle, cause other biological reactions. For instance, a heparinized surface seems to increase hemolysis (breakdown of red blood cells). When the biologically active agents wear out, the surface of the treated material returns to the untreated surface, which required the surface modification to be blood compatible in the first place. 

Early attempts to functionalize biomaterial surfaces with biological molecules were focused on improving blood compatibility of cardiovascular devices, such as the artificial heart and synthetic blood vessels, by immobilizing heparin or albumin on polyurethane or Dacron . To enhance cell adhesion to biomaterial surfaces, entire extracellular matrix (ECM) proteins, such as fibronectin and laminin, have been used directly as coatings. However, because of the nonspecific manner of whole protein adsorption, most of the cell binding capability is often lost. Using a molecular templating technique, it may be possible to select which protein(s) to absorb on biomaterial surfaces. ... 

Wilson, at Bishop College, and Eberhart and Elkowitz at University of Texas (27) have irradiated a silicone substrate in the presence of chloromethylstyrene monomer to produce a reactive graft polymer that can be quarternized with pyridine and reacted with sodium heparin to produce a thromboresistant heparinized product that has a higher blood compatibility than the untreated silicone. The same group has used essentially the same methods to create a heparin grafted polyethylene surface. 

Implanted polymeric materials can also adsorb and absorb from the body various chemicals that could also effect the properties of the polymer. Lipids (triglycerides, fatty acids, cholesterol, etc.) could act as plasticizers for some polymers and change their physical properties. Lipid absorption has been suggested to increase the degradation of silicone rubbers in heart valves (13). but this does not appear to be a factor in nonvascular Implants. Poly(dimethylsiloxane) shows very little tensile strength loss after 17 months of implantation (16). Adsorbed proteins, or other materials, can modify the interactions of the body with the polymer this effect has been observed with various plasma proteins and with heparin in connection with blood compatibility. 

These studies indicate that heparin directly affixed to a surface does not provide optimal, solution-like, anticoagulant behavior. The immobilization of heparin directly to the polymer surface resulted in alterations of the surface properties relative to control surfaces, which greatly influenced the plasma protein adsorption characteristics, a controlling factor in platelet adhesion and overall blood compatibility (12). 

Extracorporeal medical machines (e.g., artificial kidney, pump-oxygenator) perfused with blood have been an effective part of the therapeutic armamentarium for many years. These devices all rely on systemic heparinization to provide blood compatibility. Despite continuous efforts to improve anticoagulation techniques, many patients still develop coagulation abnormalities with the use of these devices (1-3). Even longer perfusion times may occur with machines such as the membrane oxygenator. In such cases, the drawbacks of systemic heparinization are multiplied (4). A number of ap-... 

The development of the heparin removal system is still at an early stage. Work currently is being directed toward (1) completing the purification of heparinase, (2) immobilizing heparinase to additional supports, and (3) testing the blood compatibility and effectiveness of heparinase reactors in vitro and in vivo. 

The initial tests of immobilized heparinase on heparinized blood were limited to short time periods (< 5 min). At later times, apparent decreases in heparin levels were observed in the control columns, although at a slower rate than with the active column. This effect may be due to blood damage occurring on the column. Such damage by Sepharose is not unexpected (37), and research is in progress to use either a different support with better blood compatibility or a Sepharose column with a lower bed-to-blood volume ratio. 

Blood compatibility of the control PCL and chitosan-g-PCL-h-PEG/heparin multilayer-deposited PCL membrane was measured using static platelet adhesion and plasma recalcification time experiments Cytocompatibity of scaffolds with endothelial cells and vascular smooth muscle cells (vSMCs)... 

Immobilization of heparin in the composite matrices (i.e., films and porous scaffolds) showed improved blood compatibility, as well as good mechanical properties and endothelial cell compatibility... 

Heparin like compound with enhanced blood compatibility. 

NHjtorNj + H ) Polypropylene (PP) Poly(Vinyl-chloride) (PVQ Polytetrafluoroethylene (FIFE) Polycarbonate (PC) Polyurethane (PU) Poly (methyl methacrylate) (PMMA) Heparin bonding for improved blood compatibility... 

It is known that sulfated polysaccharides, including natural and synthesized ones, had great blood-compatibility or even anticoagulant activity [34]. After sulfation of sodium alginate, its derivative contains both sulfate and carboxyl groups, whose chemical structure is analogous to the natural blood anticoagulant heparin. Fan et al. 

Here, we will shortly highlight a commercially available heparin-based biofunctional surface coating that is used to enhance blood compatibility of medical devices. The second example will illustrate that biomolecular function can be translated into fully synthetic systems and altered beyond the naturally... 

Li, Y, K.G. Neoh, L. Cen, and E.-T. Kang., 2003. Physicochemical and blood compatibility characterization of polypyrrole surface functionalized with heparin. Biotechnol Bioeng 84 305. 

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