Department of Biomedical Engineering, University of Michigan, Ann Arbor, 48109-0686, USA.
ASAIO J. 2011 Nov-Dec;57(6):539-44. doi: 10.1097/MAT.0b013e31823b9692.
Coagulation upon blood-contacting biomaterials remains a problem for short- and long-term clinical applications. This study examined the ability of copper(II)-doped silicone surfaces to generate nitric oxide (NO) and locally inhibit coagulation. Silicone was doped with 3-μm copper [Cu(0)] particles yielding 3 to 10 weight percent (wt%) Cu in 70-μm thick Cu/silicone polymeric matrix composites (Cu/Si PMCs). At 3, 5, 8, and 10 wt% Cu doping, the surface expression of Cu was 12.1% ± 2.8%, 19.7% ± 5.4%, 29.0% ± 3.8%, and 33.8% ± 6.5%, respectively. After oxidizing Cu(0) to Cu(II) by spontaneous corrosion, NO flux, J(NO) (mol · cm(-2) · min(-1)), as measured by chemiluminescence, increased with surface Cu expression according to the relationship J(NO) = (1.63%SA(Cu) - 0.81) × 10(-11), R(2) = 0.98, where %SA(Cu) is the percentage of surface occupied by Cu. NO flux at 10 wt% Cu was 5.35 ± 0.74 × 10(-10) mol · cm(-2) · min(-1). The clotting time of sheep blood exposed to these surfaces was 80 ± 13 seconds with pure silicone and 339 ± 44 seconds when 10 wt% Cu(II) was added. Scanning electron microscopies (SEMs) of coatings showed clots occurred away from exposed Cu dendrites. In conclusion, Cu/Si PMCs inhibit coagulation in a dose-dependent fashion related to the extent of copper exposure on the coated surface.
接触血液的生物材料的凝血仍然是短期和长期临床应用的一个问题。本研究考察了掺铜硅橡胶表面生成一氧化氮（NO）和局部抑制凝血的能力。硅橡胶中掺杂 3μm 的铜[Cu(0)]颗粒，在 70μm 厚的铜/硅橡胶聚合物基复合材料（Cu/Si PMCs）中生成 3-10 重量%（wt%）的 Cu。在 3、5、8 和 10wt% Cu 掺杂时，表面 Cu 的表达量分别为 12.1%±2.8%、19.7%±5.4%、29.0%±3.8%和 33.8%±6.5%。通过自发腐蚀将 Cu(0)氧化为 Cu(II)后，用化学发光法测量的 NO 通量，J(NO)（mol·cm(-2)·min(-1)），随着表面 Cu 表达量的增加而增加，根据关系 J(NO) = (1.63%SA(Cu)-0.81)×10(-11)，R(2)=0.98，其中%SA(Cu)是 Cu 占表面的百分比。在 10wt% Cu 时，NO 通量为 5.35±0.74×10(-10)mol·cm(-2)·min(-1)。暴露于这些表面的绵羊血的凝血时间用纯硅橡胶为 80±13 秒，加入 10wt% Cu(II)时为 339±44 秒。涂层的扫描电子显微镜（SEM）显示，血栓发生在暴露的铜枝晶之外。总之，Cu/Si PMCs 以与涂覆表面暴露的铜量相关的剂量依赖性方式抑制凝血。
