School of Molecular Bioscience, University of Sydney, NSW 2006, Australia.
Biomaterials. 2010 Nov;31(32):8332-40. doi: 10.1016/j.biomaterials.2010.07.062. Epub 2010 Aug 12.
Current endovascular stents have sub-optimal biocompatibility reducing their clinical efficacy. We previously demonstrated a plasma-activated coating (PAC) that covalently bound recombinant human tropoelastin (TE), a major regulator of vascular cells in vivo, to enhance endothelial cell interactions. We sought to develop this coating to enhance its mechanical properties and hemocompatibility for application onto coronary stents. The plasma vapor composition was altered by incorporating argon, nitrogen, hydrogen or oxygen to modulate coating properties. Coatings were characterized for 1) surface properties, 2) mechanical durability, 3) covalent protein binding, 4) endothelial cell interactions and 5) thrombogenicity. The N(2)/Ar PAC had optimal mechanical properties and did not delaminate after stent expansion. The N(2)/Ar PAC was mildly hydrophilic and covalently bound the highest proportion of TE, which enhanced endothelial cell proliferation. Acute thrombogenicity was assessed in a modified Chandler loop using human blood. Strikingly, the N(2)/Ar PAC alone reduced thrombus weight by ten-fold compared to 316L SS, a finding unaltered with immobilized TE. Serum soluble P-selectin was reduced on N(2)/Ar PAC and N(2)/Ar PAC + TE (p < 0.05), consistent with reduced platelet activation. We have demonstrated a coating for metal alloys with multifaceted biocompatibility that resists delamination and is non-thrombogenic, with implications for improving coronary stent efficacy.
目前的血管内支架的生物相容性较差,降低了其临床疗效。我们之前的研究证明,等离子体激活涂层(PAC)可以将重组人原弹性蛋白(TE)共价结合到血管细胞的主要调节剂上,从而增强内皮细胞的相互作用。我们试图开发这种涂层来增强其机械性能和血液相容性,以应用于冠状动脉支架。通过掺入氩气、氮气、氢气或氧气来改变等离子体蒸汽的组成,从而调节涂层的性能。对涂层进行了以下特性的评估:1)表面特性,2)机械耐久性,3)共价蛋白结合,4)内皮细胞相互作用,5)血栓形成。N2/Ar PAC 具有最佳的机械性能,并且在支架扩张后不会分层。N2/Ar PAC 具有轻度亲水性,并且共价结合了最高比例的 TE,从而增强了内皮细胞的增殖。使用人血在改良的 Chandler 环中评估了急性血栓形成。令人惊讶的是,与 316L SS 相比,N2/Ar PAC 单独使用可将血栓重量减少十倍,而固定 TE 后血栓重量并没有改变。N2/Ar PAC 和 N2/Ar PAC+TE 可降低血清可溶性 P-选择素(p<0.05),这与血小板活化减少一致。我们已经证明了一种用于金属合金的涂层具有多方面的生物相容性,可抵抗分层且不易血栓形成,这对提高冠状动脉支架的疗效具有重要意义。