Blood-contacting polymers

Biomaterials with Low Thrombogenicity. Poly(ethylene oxide) exhibits extraordinary inertness toward most proteins and biological macromolecules. The polymer is therefore used in bulk and surface modification of biomaterials to develop antithrombogenic surfaces for blood contacting materials. Such modified surfaces result in reduced concentrations of ceU adhesion and protein adsorption when compared to the nonmodifted surfaces. 

M.C. Frost, M.M. Reynolds, and M.E. Meyerhoff, Polymers incorporating nitric oxide releasing/gener-ating substances for improved biocompatibility of blood-contacting medical devices. Biomaterials 26, 1685-1693 (2005). 

The most widely studied synthetic polymers for blood contact applications are polyether urethane ureas ( Biomer (Ethicon)). These materials have been used in artificial hearts, as coatings for lead wires in pacemakers, have been used and are being considered for blood vessel prostheses. The success of these materials is believed to be due to preferential adsorption of albumin rather than globulin or fibrinogen which promote a clotting response. However, these materials are hydrophobic and questions of long-term effectiveness are unresolved. Particularly, these materials may shed emboli or may be susceptible to surface calcification. Thus, it may be desirable to have synthetic polymers which are hydrophilic and better resemble blood vessels [475]. 

The effect of carboxylate and/or sulfonate ion incorporation on the physical and blood contacting properties of polyurethanes was studied by Cooper and collaborators [476-478]. Specifically, propyl sulfonate and ethyl carboxylate groups were grafted onto polytetramethylene oxide-based polyurethanes. Carboxylate polymers had no statistically significant effect on canine ex vivo blood contact response, but propyl sulfonate incorporation significantly reduced platelet deposition for very short blood contact times. 

Similar results were obtained when polyethylene was modified by grafting acrylamide and cholesterol ester of N-methacryloyl-[3-alanine to get 0.3 + 0.1 mg UChD/ cm2. The efficiency of UChD bound to polymer was close to that of UChD immobilized in a polyacrylamide gel the graft copolymers sorbed from the plasma solution the amount of 0.9 mg heparin/mg of immobilized UChD. The clotting time of blood contacting the modified (but not heparinized) polyethylene was 6 min, whereas on its heparinization the time increased to 30 minutes. The latter figure was actually unaltered after sixfold repetition of the heparin sorption, subsequent washing heparin off the polymer and its repeated sorption. 

Park K, Shim HS, Dewanjee MK, et al. In vitro and in vivo studies of PEO-grafted blood-contacting cardiovascular prostheses. J Biomater Sci Polym Ed 2000 I I I 121 - I 134. 

Optimum biocompatibility of polymers in contact with cells and blood ... 

SBCs have been used for many sensitive applications including direct blood contact. These types of polymers have been subjected a broad array of medical tests, including USP, blood contact and many other screening tests. The results have all been very favorable, as shown in Table 22.3. 

To circumvent many of these undesired side effects associated with systemic heparin administration, many investigators have endeavored to immobilize heparin to blood-contacting polymers to form thromboresistant surfaces. Considering that heparin binds to the endothelium following systemic injection (I), this approach appears attractive. 

The first event that generally occurs after blood contacts a polymer surface is the formation of a protein layer at the blood-polymer interface (1). The formation of this protein layer is followed by the adherence of platelets, fibrin, and possibly leukocytes (2). Further deposition with entrapment of erythrocytes and other formed elements in a fibrin network constitutes thrombus formation. The growth of the thrombus eventually results in partial or total blockage of the lumen unless the thrombus is sheared off or otherwise released from the surface as an embolus (3). Emboli can travel downstream, lodge in vital organs, and cause infarction of tissues. The degree to which the polymer surface promotes thrombus formation and embolization, hemolysis, and protein denaturation determines its usefulness as a biomaterial (4). 

The findings of this work are (1) the properties of the polymer surface influence the composition of the protein film adsorbed upon blood contact and (2) the composition of adsorbed protein influences the subsequent thrombotic response. 

The increased longevities of animal implantations have caused unforeseen problems at the blood contacting surfaces. Increased mechanical and surface degradation of polymers employed as flexing components in... 

The mechanism for in vivo free LCFA deposition onto the polyurethane surface may result from a competitive desorption of albumin-bound LCFA s onto the lipophilic polymer soft segments. Albumin can carry upwards of 36 LCFA molecules (22), and Biomer has been shown to adsorb preferentially albumin during blood contact. 

Wabers, H.D., et al., Biostability and blood-contacting properties of sulfonate grafted polyurethane and Biomer. Journal of Biomaterial Science Polymer Edition, 1992, 4, 107-133. 

Other in vitro methods include evaluation of hemolytic properties of material extracts for blood-contacting polymers and evaluation of specific materials in their final form. An example of this is given in Table 10.1 for the standard evaluation of thermoplastic polyurethanes (PU). These standard evaluations have been developed for many commercially used biomaterials and include toxicity testing as well as me ods of final form assessment for other physical properties. 

Tubular blood-contacting polymeric materials were modified by plasma polymerization and evaluated in animals (baboons) with respect to th r c iadty to induce acute and chronic arterial thrombosis. Nine plasma polymers based on tetrafluoro-ethylene, hexafluoroethane, hexafluwoethane/H, and methane, when deposited on silicone rubber, consumed platetets at rates ranging from l.l-5.6x 10 platelets/on day. Since these values are close to the lower detection limit for this test system, tl plasma polymers were considered relatively nonthrombogenk. Thus, artificial blood tube made of polyesters, having the inner side coated with plasma-pcrfymerized tetra-fluoroethylene, is now commercially available. 

Hydrophobicity of biomedical polymers influences the biocompatibility depending on the particular application such as tissue engineering, blood contacting devices, and dental implants [35]. Polymers are dynamic structures and can switch their surface functional groups depending on the environment. For example, polymeric biomaterials need to have a hydrophilic smface for most of the applications, so that the cell-adhesive proteins present in the serum will be adsorb and promote cell adhesion and proliferation. This is achieved by snrface treatment procedures such as... 

Poly(ether-urethanes) (PU) BIOSPAN Polymer Technology Croup, Inc. Heart valves, vascular grafts, and other blood-contacting devices... 

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