Interfacial mechanics in intravascular gas embolism

我们最重要的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。通过将超薄薄膜结合到表面使固体基质具有生物功能的能力使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融合层，如低聚糖和糖蛋白，糖萼的主要成分。这些涂层还可以作为选择具有特定结合能力或治疗活性的不同大分子耦合的骨干，使血液接触仿生表面适合生物传感器或药物输送应用。人体血管内皮糖萼表面积巨大，是血管生物学和医学中研究生物工程和了解生物相容性分子基础的重要结构。人工糖萼将在心血管医学中具有直接而广泛的临床应用，也将成为心血管科学研究的有力工具。例如，仿生糖萼的创造赋予了在体外研究循环细胞和蛋白质的分子功能的能力，或者制造一个真正无反应的体外循环回路用于体外循环手术。在我们提出的应用中，我们特别关注纳米尺度的结构-功能关系，这些关系决定了仿生糖萼对血液及其衍生物接触反应的贡献。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着不良的生理反应，从而决定了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。我们将衍生和覆盖平面和管状表面的生物和合成大分子选择赋予生物相容性和治疗功能的植入式装置。我们将表征衍生化的表面纳米级结构，包括其静电轮廓。我们将使用实验方法来确定控制病理生理反应的特定分子途径，包括血栓形成和炎症反应，血液接触衍生表面。我们将评估表面耐久性和流变性。我们将结合这些目标的发现，使血液和生物相容性与特定纳米级表面结构特征相对应的功能相关。使用这些临床前研究将使识别具有介入和治疗潜力的生物材料表面结构成为可能。血液接触人工表面如透析和心脏旁路管、血管导管、支架、移植物等植入式引起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造表面的反应。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.