Regulation of polyurethane hemocompatibility and endothelialization by tethered hyaluronic acid oligosaccharides

Current synthetic vascular grafts possess a significant mechanical mismatch compared to the native vasculature and do not permit endothelialization; both of these deficiencies contribute to the relatively high rate of failure of many synthetic grafts. In this communication, we report the modification of polyurethane (PU)-based materials to impart hemocompatibility, support endothelial growth, and display vascular-appropriate mechanics. This modification was achieved by incorporating branched polyethylenimine (PEI) into the PU backbone, followed by covalent attachment of either hyaluronic acid (HA; 4.7, 64, and 104 kDa), heparin, or poly(ethylene glycol) (PEG; used as a non-adhesive control) to the PEI. This grafting chemistry resulted in comparatively dense immobilization of HA and heparin (0.062 and 2.3 microg/cm(2), respectively) to the PU-PEI surfaces. PU materials modified with HA were more effective than either PEG- or heparin-grafted materials with respect to limiting protein adsorption and platelet adhesion. Confluent, morphologically-healthy cultures of endothelial cells were achieved only on materials grafted with low molecular weight HA, but not high MW HA, heparin, or PEG. These modifications in PU chemistry were performed while retaining material mechanics in the range of native vascular tissue. Thus, this study describes the generation of materials that possess the unique ability to display excellent hemocompatibility while simultaneously supporting extensive endothelialization and retaining vascular-appropriate mechanics. The bioactivity of these materials was regulated by the molecular weight of the grafted HA, and their physical and biological properties make them promising for use as vascular grafts.