利用胶原-肝素自组装多层膜改善纯钛表面血液相容性的研究

Assemblied heparin/collagen multilayer film onto titanium surface for improving the blood-compatibility

为了改善钛表面的血液相容性,用层层自组装技术将抗凝药物肝素和细胞外基质成分之一的胶原层层交替吸附到钛表面,形成多层薄膜,使具有良好的抗凝血功能。钛通过氢氧化钠处理表面带负电,在聚赖氨酸溶液中会吸附一层带正电的聚赖氨酸,然后将其交替浸泡于带负电的肝素和带正电的胶原中形成自组装薄膜。通过傅立叶红外漫反射(FTIR)检测材料表面基团的变化,通过测水接触角的方法跟踪组装过程,通过扫描电子显微镜(SEM)观察材料表面形貌的变化。血小板黏附实验显示钛改性后表面血小板黏附量明显减少,且反映血小板激活程度的P-selectin的表达量结果也显示.钛改性后表面血小板激活程度显著降低,活化部分凝血活酶时间(APTT)和外源性凝血系统的凝血酶原时间(PT)的实验显示钛改性后表面凝血时间延长,血液相容性得到改善。研究说明这种方法对于心血管材料钛的改性有重要价值。

The collagen （col） and heparin （hep） were assembled onto the titanium surface by a layer-by-layer （LBL） self-assembly technique for improving the blood-compatibility of titanium. The positively charged poly-L-lysine （PLL） layer was first absorbed to titanium surface treated by NaOH solution. The multilayer film was then formed by alternating deposition of negatively charged heparin and positively charged collagen according to electrostatic interactions. The chemical composition, wettability and the surface topography were investigated by Fourier transform infrared spectroscopy （FTIR）, water contact angle measurement and scanning electron microscopy （SEM）, respectively. The blood compatibility was evaluated by in vitro platelet adhesion experiment, P-selectin testing, activated partial thromboplastin time （APTT） and prothrombin time （PT） measurement. The hemocompatibility results proved that, compared to untreated titanium surface, the hep/col film possessed an excellent anticoagulation performance. This study suggested that the layer-by-layer （LBL） self-assembly technique maybe have good potential for surface modification of cardiovascular devices.