A lubricious formulation exhibiting reduced thrombogenicity, cell proliferation, and protein adsorption.

The adhesion of human platelets, erythrocytes, and leukocytes, the adsorption of protein, and the proliferation of human umbilical vein endothelial cells (HUVEC) on the surface of electropolished stainless steel and the lumen of polyurethane tubing coated with Hydromer's lubricious Duality T8B formulation was evaluated. Following exposure to a platelet-enriched suspension from citrated human whole blood, stainless steel coated with this formulation exhibited significantly reduced adhesion of platelets, erythrocytes, and granulocytes. This reduction in adhesion was confirmed using an immunohistochemical method utilizing antibodies to CD41, CD235, and CD15, respectively. The proliferation of HUVEC cells were significantly reduced when cultured on coated stainless steel. This formulation was also able to significantly reduce the adsorption of plasma proteins and the major protein in tear fluid (lysozyme) to the surface of stainless steel. The nonthrombogenic properties of Duality T8B after application to the lumen of polyurethane tubing were also examined. Following a short-term (3 h) static exposure to citrated human whole blood, microscopic examination revealed that the adhesion of platelets and erythrocytes was reduced significantly, a finding confirmed using anti-CD41 and anti-CD235 antibodies in the immunohistochemical method. A long-term (12 day) study yielded essentially identical results indicating a significant reduction in the adhesion of blood components on the luminal surface of coated polyurethane tubing. In summary, these data indicate that the application of Duality T8B onto surfaces of medical devices, such as catheters, extracorporeal circuitry, and coronary stents, could aid in reducing or preventing not only thrombus formation but also the process of restenosis.

Cell adhesion and proliferation are reduced on stainless steel coated with polysaccharide-based polymeric formulations.

Hydromer's polymeric formulations F200 and F202 were evaluated after application to a synthetic substrate for effects on cell adhesion and proliferation. A significant reduction in cell adhesion was observed when cells grown on medical-grade stainless steel coated with these polymers were stained and examined under a fluorescence microscope. This reduction in cell adhesion/proliferation was confirmed when cells were isolated and analyzed by the MTS cell proliferation assay. The rate of growth of cells on F200- and F202-coated stainless steel monitored over a period of 7 days was significantly less than that observed on uncoated stainless steel, suggesting that the rate of growth of cells was reduced. The adhesion/proliferation of human umbilical vein endothelial cells (HUVEC) to coated substrates was also decreased significantly, indicating that the reduction in cell adhesion/proliferation is not restricted to only fibroblasts. Additional studies have indicated that the adhesion/proliferation of murine fibroblasts and human endothelial cells to stainless coated with a modified formulation exhibiting a high degree of lubricity was also significantly reduced. This lubricious formulation was also observed to be effective in reducing platelet adhesion, data supporting the view that lubricity also contributes to a reduction in cell and platelet adhesion. The application of these polymeric coatings on devices designed for medical implantation may not only prevent thrombus formation but may also retard the process of restenosis.