Current Techniques to Improve the Blood Compatibility of Biomaterial Surfaces

To improve the blood compatibility of medical systems two strategies are available. New materials whose surface shows the desired blood compatibility can be developed or the blood contacting surface of the medical device can be modified to improve the blood compatibility. It is no coincidence that research on novel bloodcompatible biomaterials has mainly been focussed on the development of new poly(urethanes). Poly(urethanes) have a relatively good blood compatibility and also possess optimal mechanical properties for many biomedical applications. Some examples of the development of poly(urethanes) with an improved blood compatibility have been recently reported. Okkema et al. (1) synthesized a series of poly(etherurethanes) based on poly(ethylene oxide) (PEO), poly(tetramethylene oxide) (PTMO) or mixed PEOI PTMO soft segments. Within the series the PEOcontent of the poly(urethanes) was varied. The blood compatibility of surfaces of these poIy(urethane) block copolymers was studied using a canine ex vivo shunt model. Poly(urethane) surfaces which contained higher amounts of PEO had a tendency of being more thrombogenic. Grasel et al. (2) synthesized a series of poly(urethanes) of which the urethane bonds were partially grafted with propylsulfonate groups. Within the series the degree of sulfonate substitution was varied from 0% to 20% of the available urethane bonds. The blood compatibility of surfaces of these poly(urethane) anionomers was also studied using the canine ex vivo shunt model. For polymer surfaces with low ionization levels (0-5%) no effect of the ionization on platelet and fibrinogen deposition was observed. Higher levels of ionization (15-20%) resulted in significantly increased fibrinogen deposition and decreased platelet deposition. After blood surface contact times of about 1 hour the differences in platelet deposition on the differently ionized surfaces had disappeared. Liu et al. (3) synthesized a series of PEO grafted poly(butadiene) urethanes. The PEO-contents of the graft poly(urethanes) was varied. Polymer films of the poly(urethanes) were used to study the blood compatibility of the surfaces. Poly(urethane) surfaces with moderate PEO-contents showed the highest antithrombogenicity. This observation was related to a combined effect of microphase separation of the poly(urethane) surface and the hydrogel effect of the PEO side chains. In general it is very difficult to develop a material which shows the required mechanical characteristics as well as the desired surface blood compatibility. This is one of the reasons why surface modification is a more generally applied technique to obtain blood compatible devices than the development of new materials. A combination of the two options may result in a technique in which the surface modification step is relatively simple. An example of such a technique is the work of Sanada et al. (4) who synthesized new poly(aminoetherurethaneureas) with tertiary amine groups in the main chain. Surfaces of this type of poly(urethane) could be easily heparinized by soaking them in a heparin solution. Ito et al. (5) synthesized poly(etherurethanes) with pendant methyl ester groups. After casting films, the surface methyl ester groups were saponified in a mixture of 4 N NaOH and methanol. The saponified films were then treated with citric acid and the formed carboxylic acid groups were activated with 1ethyl-3-(3-dimethylamino-propyl) carbodiim ide (EDC). Subsequently heparin was coupled by immersing the activated films in an aqueous heparin solution.