Interfacial mechanics in intravascular gas embolism

描述(由申请人提供)：总结：我们最重要的动机是生产仿生内皮细胞糖萼表面，提供与血液接触的聚合物植入物的生物相容性。通过将超薄薄膜结合到固体基质表面来实现生物功能化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物质，表面可以被剪裁成具有特定分子结构的融合层，例如低聚糖和糖蛋白，糖萼的主要成分。然后，这些涂层还可以作为连接不同大分子的骨架，这些大分子被选择为具有特定结合能力或治疗活性，使与血液接触的仿生表面适合于生物传感器或药物输送应用。考虑到人血管内皮细胞的巨大表面积，它是研究生物工程和了解血管生物学和医学中生物相容性的分子基础的重要结构。人工糖苷将在心血管医学中有直接和广泛的临床应用，也将成为心血管科学中的一种强大的研究工具。例如，创造一种仿生的糖萼使人们有能力在体外研究循环细胞和蛋白质的分子功能，或者制造用于体外循环手术的真正无反应的体外循环回路。在我们提出的应用中，特别关注纳米尺度的结构-功能关系，这些关系支配着仿生糖萼对与血液及其衍生物接触的反应的贡献。我们的全球假设是，与血液接触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利的生理反应，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。我们将在平面和管状表面衍生和涂层生物和合成大分子，以赋予植入性设备生物兼容性和治疗功能。我们将对衍生的表面纳米结构进行表征，包括其静电分布。我们将使用实验方法来确定控制血液与衍生表面接触的病理生理反应的特定分子途径，包括血栓形成和炎症反应。我们将评估表面耐久性和流变性。我们将结合这些目标的发现，使血液和生物相容性的功能关联与特定的纳米尺度表面结构特征相对应。使用这些临床前研究将能够识别具有干预和治疗潜力的生物材料表面结构。描述血液与人造表面的接触，如透析和心脏搭桥管、血管导管、支架、移植物和其他植入物，会导致血液凝结和炎症反应。这项研究将评估由生物大分子制成的仿生表面涂层，并量化血液和血液产品接触这些人造表面的反应。开发仿生表面涂层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.