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去细胞化肝脏作为一种透明的离体模型,用于血管栓塞评估。

Decellularized liver as a translucent ex vivo model for vascular embolization evaluation.

机构信息

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China; Department of Biomedical Engineering, National University of Singapore, Engineering Drive 3, Engineering Block 4, #04-08, Singapore, 117583, Singapore.

出版信息

Biomaterials. 2020 May;240:119855. doi: 10.1016/j.biomaterials.2020.119855. Epub 2020 Feb 10.

Abstract

Transarterial chemoembolization (TACE) is the preferred treatment for patients with unresectable intermediate stage hepatocellular carcinoma, however currently the development of embolic agents for TACE lacks in vitro models that closely represent the sophisticated features of the organ and the vascular systems therein. In this study, we presented a new strategy using an ex vivo liver model to provide a translucent template for evaluating embolic agents of TACE. The ex vivo liver model was developed through decellularizion of rat liver organs with preserved liver-specific vasculatures and improved transmittance of the whole liver up to 23% at 550 nm. Using this model, we investigated the embolization performances of both liquid and particle-based embolic agents, including penetration depth, embolization end-points, injection pressure and spatial distribution dynamics. We found that the embolization endpoint of liquid embolic agent such as ethiodised oil was strongly dependent on the injection pressure, and the pressure quickly built up when reaching the capillary endings, which could cause embolic agent leaking and potential tissue damages. In contrast, for particle-based embolic agents such as poly-dl-lactide microparticles and CalliSpheres® beads, their embolization endpoints were mainly determined by the particle size, whereas the particle densities close to the endpoints dramatically dropped down, which with the penetration depth represented two critical factors determining the embolic distribution. Such a decellularized organ model may open a new route to visually and quantitatively characterize embolization effects of various embolotherapies.

摘要

经动脉化疗栓塞术(TACE)是治疗不可切除的中晚期肝细胞癌的首选方法,然而,目前 TACE 栓塞剂的发展缺乏能够紧密模拟器官和其中血管系统复杂特征的体外模型。在本研究中,我们提出了一种新的策略,使用离体肝脏模型为 TACE 栓塞剂提供透明模板,以评估其性能。离体肝脏模型通过大鼠肝脏器官的去细胞化制备,保留了肝脏特异性脉管系统,并将整个肝脏的透光率提高至 550nm 时的 23%。利用该模型,我们研究了液体和基于颗粒的栓塞剂的栓塞性能,包括渗透深度、栓塞终点、注射压力和空间分布动力学。我们发现,液体栓塞剂(如乙碘油)的栓塞终点强烈依赖于注射压力,当到达毛细血管末端时,压力迅速升高,这可能导致栓塞剂泄漏和潜在的组织损伤。相比之下,对于基于颗粒的栓塞剂,如聚-dl-乳酸微球和 CalliSpheres®珠,其栓塞终点主要由颗粒大小决定,而接近终点的颗粒密度急剧下降,这与渗透深度一起代表了决定栓塞分布的两个关键因素。这种去细胞化器官模型可能为可视化和定量描述各种栓塞治疗的栓塞效果开辟新途径。

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