Thrombotic occlusion limits the usefulness of small and medium caliber synthetic vascular grafts. Initially, thrombus formation may be triggered by factors related to graft surface chemistry and texture. At later times, thrombosis occurs secondary to anastomotic intimal hyperplasia, a process involving the ingrowth and proliferation of vascular cells from the adjacent vessel. Early intimal hyperplasia may be inhibited by reducing graft thrombogenicity or by blocking the procoagulant enzyme thrombin. At later times, lesions may develop in response to the enhanced expression of growth factors, such as platelet-derived growth factor (PDGF), and graft healing responses were limited using using monoclonal antibodies against the PDGF-receptor. Efficient means for local drug delivery into grafts and blood vessels of anti-thrombotic and anti-restenotic compounds were also developed and documented. FUNDING NIH / R01HL 31469 $328,498 8/01/98 - 7/31/03 PUBLICATIONS Chinn, J.A., Sauter J.A., Phillips, R.E., Kao, W.J., Anderson, J.M, Hanson, S.R. and Ashton, T.R. Blood and tissue compatibility of modified polyester Thrombosis, inflammation, and healing. J.Biomed. Mater. Res. 39:130-140, 1998. Giese, N.A., Marijianowski, M.H., McCook, O., Hancock, A., Ramakrishnan, V., Chen, C., Kelly, A.B., Koziol, J.A., Wilcox, J.N. and Hanson, S.R. The role of alpha and beta platelet-derived growth factor receptor in the vascular response to injury in non-human primates. Arterioscler Thromb Vasc Biol. (In press). Harker, L.A., Marzec, U.M., Kelly, A.B., Chronos, N.A.F., Sundell, I.B., Hanson, S.R. and Herbert, J-M. Inhibition of stent, graft, and vascular thrombogenesis with antithrombotic enhancement by aspirin in nonhuman primates. Circulation 98:2461-2469, 1998. Markou, C.P., Lutostansky, E.M., Ku, D.N. and Hanson, S.R. A novel method for efficient drug delivery. Ann. Biomed. Eng. 26:502-511, 1998. Markou, C.P., Brown, J.E., Pursley, M.D. and Hanson, S.R. Boundary layer drug delivery using a helical catheter. J Controlled Release 53:281-288, 1998. *Stouffer, G.A., Hu, Z., Sajid, M., Li, H., Jin, G., Nakada, M.T., Hanson, S.R. and Runge, M.S. (3 integrins are upregulated after vascular injury and modulate thrombospondin- and thrombin-induced proliferation of cultured smooth muscle cells. Circulation 97:907-915, 1998. PR51RR00165-38 1/1/98 - 12/31/98 Yerkes Regional Primate Research Center
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