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.