Upstream priming of platelets for adhesion to biomaterials

血小板的上游启动以粘附到生物材料

• 批准号: 9043949
• 负责人: AARON L FOGELSON
• 金额: $ 37.25万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9043949
• 关键词: Accounting; Adhesions; Affect; Agonist; Anastomosis - action; Behavior; Biocompatible Materials; Blood; Blood Circulation; Blood Coagulation Factor VII; Blood Platelets; Blood Vessels; Blood coagulation; Blood flow; Catheters; Coagulants; Collagen; Complex; Data; Development; Device Designs; Devices; Endothelial Cells; Ethylene Oxide; Exposure to; Goals; Growth; Health; Heparin; Implant; Measurement; Modeling; Morphology; Nature; Operative Surgical Procedures; Platelet Activation; Platelet Count measurement; Platelet aggregation; Procedures; Property; Proteins; Recording of previous events; Research; Role; Site; Surface; Surface Properties; Surgical sutures; Testing; Thrombomodulin; Thromboplastin; Thrombus; Time; Translating; Vascular Graft; base; computerized tools; density; design; improved; insight; mathematical model; monolayer; novel strategies; research study; response; simulation; surface coating

 DESCRIPTION: The goals of the proposed research are to investigate how upstream platelet-agonist interactions affect the downstream platelet interactions with blood-contacting biomaterials. Almost all past research efforts in the field of biomaterial hem compatibility have focused on the local biomaterial surface properties. While these observations are essential for predicting a material's behavior in circulation, they do not reflect the whole story. For example, upstream suturing of a vascular graft creates an anastomosis (a surgical connection between biomaterial and native blood vessel) that has the potential to transiently expose different agonists to circulating platelets. Our preliminary experiments and mathematical modeling suggest that this upstream "history" of platelet-agonist interaction significantly influences plateet behavior downstream of an anastomotic site. The upstream priming effects are compounded by the fact that no blood-contacting biomaterials are perfectly hem compatible. It is hypothesized here that the magnitude of the downstream biomaterial-platelet interactions is strongly influenced by the transient platelet exposure to upstream platelet agonists that can "prime" platelets for adhesion and activation. Platelets exposed to agonists are thus more likely to adhere to and become activated by a downstream biomaterial than in the absence of such agonists. It is not known how far downstream these priming effects persist, how much time is required for the "primed" platelets to become quiescent again, and by which mechanism this phenomenon takes place. From a biomaterials point of view, this problem translates into determining the acceptable tolerance for the extent of upstream "priming". In other words, even biomaterials that have very little tendency to activate platelets may do so simply because of the upstream "priming" of platelets. The proposed study of upstream platelet-agonist effects is expected to result in a new paradigm in the field of biomaterial-derived platelet aggregation and thrombus growth; one that is not exclusively dependent on the local biomaterial surface properties but includes upstream anastomoses and perturbed blood flow. The combination of experiments and modeling in the proposed study will provide new insight into the roles of different upstream agonists and thus has the potential for establishing predictive parameters that could be used to improve the design of blood contacting devices such as catheters, grafts, and other vascular implants.

 描述：拟议研究的目标是研究上游血小板激动剂相互作用如何影响下游血小板与血液接触生物材料的相互作用。几乎所有过去在生物材料边缘相容性领域的研究工作都集中在局部生物材料表面特性上。这些观察结果对于预测材料在循环中的行为至关重要，但它们并不能反映整个情况，例如，血管移植物的上游缝合会产生吻合（生物材料和生物材料之间的外科连接）。我们的初步实验和数学模型表明，血小板-激动剂相互作用的上游“历史”显着影响吻合部位下游的血小板行为。由于没有血液接触的生物材料完全兼容，因此下游生物材料-血小板相互作用的程度受到短暂的血小板暴露于上游血小板的强烈影响。因此，与没有此类激动剂的情况相比，暴露于激动剂的血小板更有可能粘附到下游生物材料上并被下游生物材料激活，目前尚不清楚这些启动作用会持续到下游多远。 “引发”的血小板再次静止需要多长时间，以及这种现象发生的机制从生物材料的角度来看，这个问题转化为确定上游范围的可接受的耐受性。换句话说，即使生物材料具有很少的激活血小板的倾向，也可能仅仅因为血小板的上游“引发”作用而提出的上游血小板激动剂效应研究预计将产生一个新的范例。生物材料衍生的血小板聚集和血栓生长领域；这一领域不仅取决于局部生物材料表面特性，还包括上游吻合和扰动血流。将为不同上游激动剂的作用提供新的见解，因此有可能建立预测参数，可用于改进血液接触装置（如导管、移植物和其他血管植入物）的设计。