Approaches to thromboresistant materials are discussed including passivation; incorporation and/or release of anticoagulants, antiplatelet agents, thrombolytic agents; and mimicry of the vascular endothelium.
To examine the role of heme oxygenase (HO)-1 in the pathophysiology of vascular diseases, we generated mice deficient in both HO-1 and apolipoprotein E (HO-1-/-apoE-/-). Despite similar total plasma cholesterol levels in response to hypercholesterolemia, HO-1-/-apoE-/- mice, in comparison with HO-1+/+apoE-/- mice, had an accelerated and more advanced atherosclerotic lesion formation. In addition to greater lipid accumulation, these advanced lesions from HO-1-/-apoE-/- mice contained macrophages and smooth muscle alpha-actin-positive cells. We further tested the role of HO-1 on neointimal formation in a mouse model of vein graft stenosis. Autologous vein grafts in HO-1-/- mice showed robust neointima consisting of alpha-actin-positive vascular smooth muscle cells (VSMC) 10 days after surgery in comparison to the smaller neointima formed in autologous vein grafts in HO-1+/+ mice. However, at 14 days after surgery, the neointima from composite vessels of HO-1-/- mice was composed mainly of acellular material, indicative of substantial VSMC death. VSMC isolated from HO-1-/- mice were susceptible to oxidant stress, leading to cell death. Our data demonstrate that HO-1 plays an essential protective role in the pathophysiology of atherosclerosis and vein graft stenosis.
Poly(N-vinylpyrrolidone) (PVP), an important water soluble synthetic polymer, has many desirable properties including low toxicity, chemical stability, and good biocompatibility. Since PVP is hemocompatible and physiologically inactive, it has been used as a blood plasma substitute. Surface modification with PVP has been investigated extensively over the past few years as a means of preventing nonspecific protein adsorption. PVP may therefore be seen as a promising antifouling surface modifier comparable to poly(ethylene glycol) (PEG). In this review, various approaches for the design and preparation of PVP-modified surfaces are summarized and potential biomedical applications of these PVP-modified materials are indicated. Finally, some perspectives on future research on PVP for surface modification are discussed.
Well-controlled poly(N-vinylpyrrolidone) (PVP)-grafted silicon surfaces were prepared by surface-initiated atom transfer radical polymerization (SI-ATRP) with 1,4-dioxane/water mixtures as solvents and CuCl/5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane (Me6TATD) as a catalyst. The thickness of the PVP layer on the surface increased with reaction time, suggesting that the ATRP grafting of N-vinylpyrrolidone (NVP) from the silicon surfaces was a well-controlled process. The water contact angle and X-ray photoelectron spectroscopy (XPS) were used to characterize the modified surfaces. The protein adsorption property of the PVP-grafted surfaces was evaluated using a radiolabeling method. Compared with unmodified silicon surfaces, a Si-PVP60 surface with a PVP thickness of 15.06 nm reduced the level of adsorption of fibrinogen, human serum albumin (HSA), and lysozyme by 75, 93, and 81%, respectively. Moreover, the level of fibrinogen adsorption decreases gradually with an increase in PVP thickness. However, no significant difference in fibrinogen adsorption was found when the PVP layer was thicker than the critical thickness of 13.45 nm.
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