Interfacial mechanics in intravascular gas embolism

描述（由申请人提供）：总结我们的主要动机是生产仿生内皮细胞糖萼表面，提供血液接触聚合物植入物的生物相容性。通过将超薄膜结合到表面上来生物功能化固体基质的能力使得仿生膜结构的生物工程构建成为可能。使用新的合成和附着化学，表面可以被定制为具有特定分子结构的汇合层，例如寡糖和糖蛋白，糖萼的主要成分。然后，这些涂层还可以用作用于偶联不同大分子的骨架，所述大分子被选择为具有特异性结合能力或治疗活性，使得血液接触仿生表面适合于生物传感器或药物递送应用。鉴于人血管内皮糖萼的巨大表面积，它是生物工程研究和了解血管生物学和医学生物相容性的分子基础的重要结构。人工糖萼在心血管医学中具有直接和广泛的临床应用，也将成为心血管科学中强有力的研究工具。例如，仿生糖萼的产生赋予了在体外研究循环细胞和蛋白质的分子功能或制造用于心肺旁路手术的真正无反应的体外循环回路的能力。在我们提出的应用程序中，特别注意纳米级的结构-功能关系，管理的仿生glycocalyx的贡献与血液及其衍生物接触的反应。我们的总体假设是，接触血液的涂层生物材料的化学成分和纳米级表面结构特征控制不良生理反应，从而确定生物或血液相容性的功能极限。我们将通过三个具体目标来检验这一假设。我们将用生物和合成大分子衍生化和涂覆平面和管状表面，以赋予植入式器械生物相容性和治疗功能。我们将表征衍生的表面纳米级结构，包括其静电轮廓。我们将使用实验方法来确定特定的分子途径，包括血栓形成和炎症反应，血液接触衍生表面的病理生理反应。我们将评估表面耐久性和流变性。我们将结合这些目标的研究结果，使血液和生物相容性的功能相关性对应于特定的纳米级表面结构特征。使用这些临床前研究将能够识别具有介入和治疗潜力的生物材料表面结构。血液与人工表面接触，如透析和心脏旁路管、血管导管、支架、移植物和其他植入物，会导致血液凝固和炎症反应。这项研究将评估由生物大分子制成的仿生表面涂层，并量化血液和血液制品接触这些人工表面的反应。仿生表面涂层的开发是提高医疗器械生物相容性的有力手段。

DESCRIPTION (provided by applicant): Summary Our overriding motivation is to produce biomimetic endothelial cell glycocalyx surfaces that provide biocompatibility of blood-contacting polymeric implants. The ability to biofunctionalize solid substrates by binding ultra thin films onto the surface makes possible the bioengineered construction of biomimetic membrane structures. Using novel synthetic and attachment chemistries, surfaces can be tailored to have a confluent layer of specific molecular structures such as oligosaccharides and glycoproteins, major constituents of the glycocalyx. These coatings can then also serve as a backbone for coupling different macromolecules selected to have specific binding capabilities or therapeutic activities, making the blood- contacting biomimetic surface suitable for biosensor or drug delivery applications. Considering the human vascular endothelial glycocalyx's vast surface area, it is an important structure for study in bioengineering and understanding the molecular basis of biocompatibility in vascular biology and medicine. An artificial glycocalyx will have direct, and broad, clinical application in cardiovascular medicine and will also serve as a powerful research tool in the cardiovascular sciences. For example, the creation of a biomimetic glycocalyx confers the ability to study molecular function of circulating cells and proteins in vitro or to manufacture a truly nonreactive extracorporeal circulation circuit for use in cardiopulmonary bypass surgery. In our proposed application, particular attention is paid to nano-scale structure-function relationships that govern the biomimetic glycocalyx's contribution to responses to contact with blood and its derivatives. Our global hypothesis is that the chemical composition and nano-scale surface structure features of coated biomaterials contacting blood control adverse physiological responses and thus determine the functional limits of bio- or hemo-compatibility. We will test this hypothesis via three Specific Aims. We will derivatize and coat planar and tubular surfaces with biological and synthetic macromolecules selected to impart biocompatibility and therapeutic function to implantable devices. We will characterize the derivatized surface nano-scale structure, including its electrostatic profile. We will use experimental methods to identify specific molecular pathways governing pathophysiological responses, including thrombogenic and inflammatory responses, to blood contact with derivatized surfaces. We will assess surface durability and rheology. We will incorporate findings from these aims to make functional correlates of hemo- and bio- compatibility corresponding to specific nanoscale surface structural features. Use of these preclinical studies will enable identification of biomaterial surface constructs having interventional and therapeutic potential. Narrative Blood contact with artificial surfaces such as dialysis and cardiac bypass tubing, vascular catheters, stents, grafts and other implantable causes blood clotting and inflammatory responses. This research will evaluate biomimetic surface coatings made from biomacromolecules and quantify responses of blood and blood products contacting those artificial surfaces. The development of biomimetic surface coatings is a powerful method to increase medical device biocompatibility.