具有集成血管床的微孔中3D细胞聚集体的血管化
vascularization of 3D cell aggregates in microwells with integrated vascular beds.
作者信息
Fois Maria G, Tahmasebi Birgani Zeinab N, López-Iglesias Carmen, Knoops Kèvin, van Blitterswijk Clemens, Giselbrecht Stefan, Habibović Pamela, Truckenmüller Roman K
机构信息
Department of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 40, 6229 ER, Maastricht, the Netherlands.
Microscopy CORE Lab, Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, the Netherlands.
出版信息
Mater Today Bio. 2024 Sep 19;29:101260. doi: 10.1016/j.mtbio.2024.101260. eCollection 2024 Dec.
Most human tissues possess vascular networks supplying oxygen and nutrients. Engineering of functional tissue and organ models or equivalents often require the integration of artificial vascular networks. Several approaches, such as organs on chips and three-dimensional (3D) bioprinting, have been pursued to obtain vasculature and vascularized tissues . This technical feasibility study proposes a new approach for the vascularization of 3D microtissues. For this, we thermoform arrays of round-bottom microwells into thin non-porous and porous polymer films/membranes and culture vascular beds on them from which endothelial sprouting occurs in a Matrigel-based 3D extra cellular matrix. We present two possible culture configurations for the microwell-integrated vascular beds. In the first configuration, human umbilical vein endothelial cells (HUVECs) grow on and sprout from the inner wall of the non-porous microwells. In the second one, HUVECs grow on the outer surface of the porous microwells and sprout through the pores toward the inside. These approaches are extended to lymphatic endothelial cells. As a proof of concept, we demonstrate the vascularization of spheroids from human mesenchymal stem cells and MG-63 human osteosarcoma cells. Our results show the potential of this approach to provide the spheroids with an abundant outer vascular network and the indication of an inner vasculature.
大多数人体组织都拥有提供氧气和营养物质的血管网络。功能性组织和器官模型或等效物的工程构建通常需要整合人工血管网络。人们已经采用了几种方法,如芯片上的器官和三维(3D)生物打印,来获得脉管系统和血管化组织。这项技术可行性研究提出了一种用于3D微组织血管化的新方法。为此,我们将圆底微孔阵列热成型为薄的无孔和多孔聚合物薄膜/膜,并在其上培养血管床,基于基质胶的3D细胞外基质中会在内皮细胞从这里发生芽生。我们展示了两种用于微孔集成血管床的可能培养配置。在第一种配置中,人脐静脉内皮细胞(HUVECs)在无孔微孔的内壁上生长并从中发芽。在第二种配置中,HUVECs在多孔微孔的外表面上生长,并通过孔隙向内部发芽。这些方法扩展到了淋巴管内皮细胞。作为概念验证,我们展示了来自人间充质干细胞和MG-63人骨肉瘤细胞的球体的血管化。我们的结果显示了这种方法为球体提供丰富的外部血管网络以及内部脉管系统迹象的潜力。