Aye San Seint Seint, Fang Zhongqi, Wu Mike C L, Lim Khoon S, Ju Lining Arnold
School of Biomedical Engineering, The University of Sydney, Darlington, NSW 2008, Australia.
Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006, Australia.
Biomater Sci. 2025 Feb 25;13(5):1131-1160. doi: 10.1039/d4bm01354a.
Thrombosis, a major cause of morbidity and mortality worldwide, presents a complex challenge in cardiovascular medicine due to the intricacy of clotting mechanisms in living organisms. Traditional research approaches, including clinical studies and animal models, often yield conflicting results due to the inability to control variables in these complex systems, highlighting the need for more precise investigative tools. This review explores the evolution of thrombosis models, from conventional polydimethylsiloxane (PDMS)-based microfluidic devices to advanced hydrogel-based systems and cutting-edge 3D bioprinted vascular constructs. We discuss how these emerging technologies, particularly vessel-on-a-chip platforms, are enabling researchers to control previously unmanageable factors, thereby offering unprecedented opportunities to pinpoint specific clotting mechanisms. While PDMS-based devices offer optical transparency and fabrication ease, their inherent limitations, including non-physiological rigidity and surface properties, have driven the development of hydrogel-based systems that better mimic the extracellular matrix of blood vessels. The integration of microfluidics with biomimetic materials and tissue engineering approaches has led to the development of sophisticated models capable of simulating patient-specific vascular geometries, flow dynamics, and cellular interactions under highly controlled conditions. The advent of 3D bioprinting further enables the creation of complex, multi-layered vascular structures with precise spatial control over geometry and cellular composition. Despite significant progress, challenges remain in achieving long-term stability, incorporating immune components, and translating these models to clinical applications. By providing a comprehensive overview of current advancements and future prospects, this review aims to stimulate further innovation in thrombosis research and accelerate the development of more effective, personalized approaches to thrombosis prevention and treatment.
血栓形成是全球发病和死亡的主要原因,由于生物体内凝血机制的复杂性,在心血管医学中提出了一项复杂的挑战。传统的研究方法,包括临床研究和动物模型,由于无法控制这些复杂系统中的变量,往往会产生相互矛盾的结果,这凸显了对更精确研究工具的需求。本综述探讨了血栓形成模型的演变,从传统的基于聚二甲基硅氧烷(PDMS)的微流控装置到先进的基于水凝胶的系统以及前沿的3D生物打印血管构建体。我们讨论了这些新兴技术,特别是芯片上血管平台,如何使研究人员能够控制以前难以管理的因素,从而提供了前所未有的机会来确定特定的凝血机制。虽然基于PDMS的装置具有光学透明性且易于制造,但其固有的局限性,包括非生理性的刚性和表面特性,推动了基于水凝胶的系统的发展,这些系统能更好地模拟血管的细胞外基质。微流控技术与仿生材料和组织工程方法的整合,导致了能够在高度可控条件下模拟患者特异性血管几何形状、流动动力学和细胞相互作用的复杂模型的开发。3D生物打印的出现进一步使得能够创建具有精确几何形状和细胞组成空间控制的复杂多层血管结构。尽管取得了重大进展,但在实现长期稳定性、纳入免疫成分以及将这些模型转化为临床应用方面仍存在挑战。通过全面概述当前的进展和未来前景,本综述旨在激发血栓形成研究的进一步创新,并加速开发更有效、个性化的血栓形成预防和治疗方法。