Effect of Uremic Toxins and Methoxy-PEO Chain Density on Plasma Protein Adsorption.

Abstract

Protein adsorption can direct the host response to blood-contacting biomaterials. Poly(ethylene oxide) (PEO) is commonly employed to minimize nonspecific protein adsorption. Although chain density has been observed to play a role in the inherent resistance of protein adsorption by end-tethered films of PEO, only a few papers correlate the change in PEO chain densities with the adsorbed plasma protein composition. Almost all studies rely upon blood from healthy patients for these studies even though they are applied to the unhealthy. In the case of patients with kidney failure, there is a remarkable change in the blood composition due to retained metabolites. In the pursuit of personalized dialysis, we must address this dearth in the literature regarding the effect of metabolite accumulation in the blood compartment on the adsorption of protein to blood-contacting biomaterials. To this end, surface films of different methoxy-PEO (mPEO) chain densities were used to evaluate the changes in adsorbed proteins in the presence of uremic metabolites (i.e., uremic toxins). End-tethered mPEO films were characterized using contact angles, ellipsometry, and X-ray photoelectron spectroscopy. Plasma protein adsorption was conducted with and without uremic toxins commonly found in patients with end stage kidney disease, and the adsorbed protein profile was identified using immunoblots. It was found that the presence of uremic toxins led to a notable increase in the adsorption of almost all of the proteins. It was evident that while chain density plays a role in overall protein resistance, the effect of uremic toxins led to substantial increases in adsorbed proteins and needs to be considered when designing next-generation blood-contacting materials.