BIOLOGICAL INTERACTIONS WITH POLYMER BIOMATERIALS EVALUATED AT MICROSCOPIC AND NANOSCOPIC LEVELS

Abstract

Polymer biomaterials are used in a variety of blood-contacting medical devices. In particular, poly(urethaneurea) (PUU) based biomaterials have proven well-suited for devices due to their good mechanical properties and superior blood compatibility compared to other synthetic materials. This has largely been attributed to the phenomena of microphase separation, as the PUU copolymer separates into distinct “hard” and “soft” microphases. Although a variety of evidence relating microphase separation and blood compatibility exists in the literature, there is no direct evidence relating the two phenomena at a molecular level. We have attempted to leam more about the biological interactions with polymer biomaterials including PUU materials by utilizing high resolution fluorescence microscopy and atomic force microscopy (AFM). AFM was used to characterize the microphase structure of a series of PUU films of varying hard segment/soft segment ratio and to determine the interactions of proteins with synthetic polymer materials under aqueous buffer conditions. Fluorescence microscopy with immunohistochemical staining was used to study platelet interactions with PUU materials under in-vitro conditions as well as protein interactions with PUU blood sacs retrieved from total artificial heart implanted animals. AFM images demonstrated a characteristic microphase structure in the PUU films best described as randomly oriented cylinders with occasional spherical domains. High-resolution studies of individual plasma proteins on hydrophobic polymer materials reveal tertiary structures consistent with what others have observed previously on ultrasmooth model biomaterial surfaces. The fluorescence microscopy images demonstrated protein deposition aligned with the expected direction of blood flow in the implanted devices. Taken together, these data provide insight into the nature of biomaterial/biological interactions under physiologically relevant conditions.