Adsorption of Treponema Pallidum Protein to Functionalized Alkanethiol Self-Assembled Monolayers for Improving Biocompatibility

这项由材料研究部生物材料项目授予肯塔基大学的奖项是为了研究使用抗原蛋白伪装在接触血液的医疗设备上创建生物相容性表面。血液接触器的临床应用正变得越来越普遍。虽然这些设备中的许多已经在患者身上成功使用多年，并被认为对治疗有益，但它们的性能并不理想。一旦植入，其中一些设备会完全被蛋白质覆盖，并导致血栓的形成，这可能会导致严重的问题。获得这一奖项后，PI将研究一种名为Tp0483的细菌蛋白与人血浆纤维连接蛋白的结合，以利用这一表面作为抗原性伪装来创建血液相容性表面。这项研究的总体目标是研究名为Tp0483的细菌蛋白对表面的修饰，这种蛋白作为抗原蛋白伪装可能在血液相容表面和系统中具有潜在的应用。早期的研究表明，这种细菌蛋白与可溶性二聚体纤维连接蛋白结合，结合的纤维连接蛋白为细菌提供抗原性伪装。在这项研究中，Tp0483将通过自组装单分子膜吸附到表面，并将利用表面等离子体共振技术研究纤维连接蛋白(FN)和纤维连接蛋白片段FN 7-10的吸附。此外，将使用原子力显微镜(AFM)研究FN和FN 7-10在Tp0483上的吸附机制，以确定这些蛋白质的结合强度。早期，已使用许多不同的方法来创建血液相容性表面，虽然这些过程已被证明可以改善血液相容性，但到目前为止，创建完全血液相容性表面是不可能的。在这项研究中，抗原性伪装将被用来在植入式医疗设备上创建血液相容性表面，如果成功，将对这些设备的使用产生很大影响。此外，关于纤维连接蛋白与细菌蛋白TP0483结合机制的信息将为细菌如何利用该蛋白进行抗原伪装提供更好的理解。虽然这项研究的重点是使用蛋白质Tp0483来改善血液接触材料的相容性，但这一结果将为未来的研究奠定基础，以便研究其他已知的抗原性伪装的自然存在的蛋白质。该奖项将为研究生、本科生和高中生提供参与这项研究的机会，并接受工程和材料科学方面的多学科培训。

This award to University of Kentucky by the Biomaterials program in the Division of Materials Research is to study the use of antigenic protein disguise to create biocompatible surfaces on blood-contacting medical devices. Clinical uses of blood-contacting devices are becoming more common. While many of these devices have been successfully used in patients for many years and are judged to be therapeutically beneficial, their performance is less than optimal. Upon implantation, some of these devices become completely coated with proteins and lead to formation of thrombi, which can cause significant problems. With this award, the PI will study binding of a bacterial protein called Tp0483 with human plasma fibronectin to create a hemocompatible surface by utilizing this as an antigenic disguise. The overall objective of this investigation is to study surface modifications by bacterial proteins called Tp0483, which as antigenic protein disguise may have potential applications in hemocompatible surfaces and systems. Earlier studies have shown that this bacterial protein binds with soluble dimeric fibronectin and the bound fibronectin serves an antigenic disguise for the bacterium. In this study, Tp0483 will be adsorbed to surfaces using self-assembled monolayer and the adsorption of fibronectin (FN) and a fibronectin fragment FN 7-10 will be investigated using surface plasmon resonance. In addition, the mechanism of adsorption of the FN and FN 7-10 to the Tp0483 will be studied using Atomic Force Microscopy (AFM) to determine binding strength of these proteins.Earlier, many different approaches have been used to create blood-compatible surfaces and while these processes have been shown to improve blood-compatibility, the creation of a wholly hemocompatible surface has, thus far, been unachievable. In this study, antigenic disguise will be used to create hemocompatible surfaces on implantable medical devices, and if successful, would have high impact in the use of these devices. In addition, information obtained on mechanisms of fibronectin binding to the bacterial protein TP0483 will provide a better understanding as to how the bacteria uses this protein for antigenic disguise. While this study focuses specifically on using the protein, Tp0483 for improving compatibility of blood-contacting materials, the results will form the basis for future studies where other naturally occurring proteins known for antigenic disguise can be studied. This award will provide graduate, undergraduate and high school students will opportunity to participate in this research and receive multidisciplinary training in engineering and materials science.