School of Mechanics and Safety Engineering, Zhengzhou University, Zhengzhou, China.
Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts, USA.
Biotechnol Bioeng. 2021 Feb;118(2):963-978. doi: 10.1002/bit.27626. Epub 2020 Nov 24.
Most tissue-engineered blood vessels are endothelialized by static cultures in vitro. However, it has not been clear whether endothelial cell-shedding and local damage may occur in an endothelial layer formed by static cultures under the effect of blood flow shear postimplantation. In this study, we report a bionic and cost-effective vascular chip platform, and proved that a static culture of endothelialized tissue-engineered blood vessels had the problem of a large number of endothelial cells falling off under the condition imitating the human arterial blood flow, and we addressed this challenge by regulating the flow field in a vascular chip. Electrospun membranes made of highly oriented or randomly distributed poly(ε-caprolactone) fibers were used as the vascular scaffolds, on which endothelial cells proliferated well and eventually formed dense intima layers. We noted that the monolayers gradually adapted to the artery-like microenvironment through the regulation of chip flow field, which also revealed improved cellular orientations. In conclusion, we have proposed a vascular chip with adaptive flow patterns to gradually accommodate the statically cultured vascular endothelia to the shear environment of arterial flow field and enhanced the orientation of the endothelial cells. This strategy may find numerous potential applications such as screening of vascular engineering biomaterials and maturation parameters, studying of vascular biology and pathology, and construction of vessel-on-a-chip models for drug analysis, among others.
大多数组织工程血管都是通过体外静态培养内皮化的。然而,在植入后血流剪切力的作用下,静态培养形成的内皮层中是否会发生内皮细胞脱落和局部损伤,目前还不清楚。在本研究中,我们报告了一种仿生且具有成本效益的血管芯片平台,并证明在模拟人体动脉血流的条件下,静态培养的内皮化组织工程血管会有大量内皮细胞脱落的问题,我们通过调节血管芯片中的流场解决了这一挑战。我们将取向或无规分布的聚己内酯纤维的静电纺丝膜用作血管支架,内皮细胞在其上增殖良好,最终形成密集的内皮层。我们注意到,通过芯片流场的调节,单层细胞逐渐适应了类似动脉的微环境,同时也显示出细胞取向的改善。总之,我们提出了一种具有自适应流场的血管芯片,可以逐渐使静态培养的血管内皮适应动脉流场的剪切环境,并增强内皮细胞的取向。这种策略可能会在筛选血管工程生物材料和成熟参数、研究血管生物学和病理学、构建用于药物分析的芯片上血管模型等方面有广泛的应用前景。