The Molecular Mechanism Of Interface Reaction Between Titanium Dioxide And Blood Plasma

Cardiovascular and cerebrovascular disease is one type of diseases which will serviously threaten the health and life of human beings.Coagulation、thrombosis and anticoagulation complication are the main problem occurred by cardiovascular biomaterial clinic application which will impede cardiovascular biomaterial’s development. When improve and develope the new generation bloodcontacting biomaterial, three points will be listed:understanding the interface reaction between materials with blood (especially the material-protein interface);exploring the key link and factor of coagulation induced by material; developing the anticoagulation mechanism from molecular level. In the past 10 years our group members focused on the improvement of anticoagulation material (titanium dioxide) for blood-conatcting device application. They have fabricated many titianium dioxide films with excellent blood compatibility. Based on these plentiful experiences, we choose two kinds of model material with classic anticoagulation as the research objects. One is titanium dioxide after annealing, the other is titanium dioxide after surface electrochemical n-type doping. Accurate and advanced technologies on interface such as AFM, CD, MICRODSC, FCM and immunochemistry are applied to monitor the interaction betweent blood and model material.The final aim of this study is to elucidate the anticoagulation mechanism from molecular level.As two types of simple and effective technologies, vacuum annealing and surface chemical doping are choosen to acquire a series of titanium dioxide materal with differen anticoagulation porperties. Their surface chemical and physical charactetistics are measured from full aspects. The results suggest The oxygen vacancies created by vacuum annealing (especially at 800℃), and it induces the surface hydroxyl and basic hydroxyl content increase, furthermore, the increase of hydroxyl content resulted in surface basic component and the hydrophiliity increase, and the blood compatibility of the material improved. For the titanium dioxide modified by surface electrochemical n-type doping, more electrons will be transferred into the material surface and neutralize the Lewis and Bronsted-Lowry acid component to reduced the acid hydroxyl and incease the percentage of basic hydroxyl. Furthermore, more negative potential will be acquired on the material surface.A series of coagulteion test suggest the modified titanium dioxide possess favorable hemocompatibility and anti-thrombosis property.The QCM-D technology is adopted to monitor the interaction between titanium dioxide modified by surface electrochemical n-type doping with differentcomponents in blood plasma in situ. These conmponents include fibrinogen, hageman factor,platelet poor plasma and platelet rich plasma.the results show the fibrinogen with high concentration will adsob on the surface by end-on conformation while the fibrinogen with low concentration will adsorb by side-on conformation.In low concentration,the material will effect the fibrinogen conformation strongly.The process of fibrinogen adsorption is divided by two steps and the exposure of active domain on the fibrinogen is less. The Hageman factor will adsorb and be activated more on the modified surface that will startup the clotting cascade. The quantity of thrombus is relative with the adsorption of fibrinogen.Multiple accurate and advanced technologies such as AFM, CD,Microdsc,FCM immunochemistry are applied to investigate the fibrinogen conformation on the interface.The results of morphology、immunochemical function and thermodynamic change of fibrinogen indicate the fibrinogen will favorably adsorb on the model material surface by aC chain in a side-on way to reduce the exposure of active motif and furthermore thrombosis.In conclusion, enhancement the negative potential of titanium dioxide can be regarded as a useful method to improve the bloodcompatibility of titanium dioxide. The surface with more negative charge will regulate the fibrinogen adsorbing by aC chain in a side-on way to reduce the exposure of active motif and furthermore thrombosis.This study provides reasonable explanations for the mechanism of titanium dioxide anticoagulation and potential means for suitable blood contacting material designing.