模拟剪切率梯度诱导人体出血模型的气血界面工程微流控装置

Shobhit Das, Shilpi Pandey, Oliver Hayden
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摘要

微流控技术已成为研究复杂生物学过程的有力工具,其精确性和可控性都得到了提高。我们设计了一种微流控芯片来模拟类似人体的微血管网络,精确控制通道的几何形状和流动条件。通过模拟出血时的血流动态,我们成功地观察到了血小板的实时相互作用以及伤口处剪切率梯度引起的血小板聚集。血小板动力学主要受血管物理机械条件和血管损伤部位附近血液病理生理条件的影响。这种微流控平台有助于研究血小板的粘附、活化和血凝块的形成,为研究血小板聚集和血凝块的时空动态提供了独特的机会。我们的研究结果揭示了血栓形成和血小板介导的聚集的复杂机制,与传统的动物模型相比,更准确、更动态地反映了人体止血过程。在传统方法中,由于小鼠和人类在解剖和病理上的相似性,人类出血模型要在小鼠身上进行试验。这项研究将简化血液和血管条件并使之标准化。此外,它还为有针对性的治疗干预铺平了道路,有助于治疗出血性疾病和加强促进伤口有效闭合的临床策略。最终,这项研究展示了微流体技术彻底改变止血研究的潜力,并为凝血障碍领域个性化医学方法的发展开辟了新途径。
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Air-blood interface engineered microfluidic device to mimic shear rate gradient induced human bleeding model
Microfluidic technology has emerged as a powerful tool for studying complex biological processes with enhanced precision and control. A microfluidic chip was designed to emulate human-like microvascular networks with precise control over channel geometry and flow conditions. By simulating blood flow dynamics during bleeding events, we successfully observed the real-time interactions of platelets and their aggregation induced by shear rate gradient at the wound site. Platelet dynamics is primarily influenced by physico-mechanical condition of blood vessels with pathophysiological condition of blood at close proximity of vascular injury site. This microfluidic platform facilitated the investigation of platelet adhesion, activation, and clot formation, providing a unique opportunity to study the spatiotemporal dynamics of platelet aggregation and blood clot. Our findings shed light on the intricate mechanisms underlying thrombus formation and platelet-mediated aggregation, offering a more accurate and dynamic representation of human haemostasis compared to traditional animal models. In the conventional approach, the human bleeding model is tried on mouse due to anatomy and pathological similarities between mouse and humans. This study will simplify and standardize the blood and vasculature conditions. The microfluidic-based replication of the bleeding model holds significant promise in advancing our understanding of clotting disorders and wound healing processes. Furthermore, it paves the way for targeted therapeutic interventions in managing bleeding disorders and enhancing clinical strategies for promoting efficient wound closure. Ultimately, this study demonstrates the potential of microfluidics to revolutionize haemostasis research and opens up new avenues for the development of personalized medicine approaches in the field of clotting disorders.
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