| Cardiovascular devices implanted within the vasculature are subjected to non-specific adsorption of plasma proteins. This initiates the blood coagulation cascade and platelet adhesion and activation, leading to thrombus formation. In this thesis Heparin Alkyl Diblock (HAD) surfactants were developed to improve the blood compatibility of cardiovascular biomaterials. The material designs involved using heparin, a natural anticoagulant, to inhibit coagulation pathway enzymes and mimic the cell glycocalyx to provide a repulsive force field to inhibit non-specific protein adsorption.; Type AB linear (HAD Cn, n = 6,10,12,18) and branched (HAD nx 18, n = 2,3,4) heparin surfactants were synthesized by end point coupling primary and secondary alkyl amines to heparin via reductive amination. Surfactant yields (83–4%) and anticoagulant activity (149.8 ± 3.7–39.6 ± 0.6 IU/mg) decreased with increased branching and hydrocarbon number. Surfactant adsorption, self assembly and molecular packing of HAD surfactants at the air/liquid and liquid/solid interface were a function of the number of hydrocarbons in the surfactant alkyl segment and the presence or absence of an ionic liquid phase. Increased molecular packing was observed at the air/PBS and PBS/graphite interface, relative to aqueous interfaces, resulting from buffer cations shielding heparin's negatively charged sulfate and carboxyl groups. At the PBS/graphite interface, the surfactant's apparent heparin head group cross section decreased in diameter (1.84 to 1.05 nm) and increased in tilt angle (75.7 to 81.9°) with increasing alkyl carbon number (n = 6 to 18). The heparin head group reached a minimum diameter, equivalent to the surfactant's diameter at the air/PBS interface (0.57 nm) just prior to 36 hydrocarbons in the surfactant. For surfactants with 36 to 78 hydrocarbons, the surfactant's heparin head group oriented normal to the graphite surface and alkyl overlap or interdigitation increased (0.02 to 0.59 nm) with increasing hydrocarbon number (n = 36 to 78).; Under aqueous flow (1ml/min) the adhesion stability of linear heparin surfactants (n = 6–18), adsorbed on polyethylene, increased with increasing alkyl carbon number. However, on polyurethane, only trioctadecyl HAD 3x18 surfactant remained stable. In in vitro studies, the trioctadecyl heparin surfactant coating demonstrated reduction in static (78%) and shear (67%) platelet adhesion, and reduction in three platelet activation markers relative to a glass control. In vivo experiments, which examined restenosis in a porcine coronary model, demonstrated that the heparin surfactant coating reduced in-stent neointimal formation by 30%, relative to the bare stainless steel control stent.; In this research, surface active properties of heparin surfactants were constructively manipulated to maximize the adsorption and adhesion to cardiovascular biomaterials. By maximizing the number of hydrocarbons through alkyl branching and utilizing the hydrophobic effect, heparin-alkyl amphiphiles self assembled into dense, homogeneous, stable layers on hydrophobic surfaces. The heparin surfactant coating provided a nonthrombogenic surface with reduced in-stent restenosis for cardiovascular implants. |
