Zhang Boyang, Montgomery Miles, Chamberlain M Dean, Ogawa Shinichiro, Korolj Anastasia, Pahnke Aric, Wells Laura A, Massé Stéphane, Kim Jihye, Reis Lewis, Momen Abdul, Nunes Sara S, Wheeler Aaron R, Nanthakumar Kumaraswamy, Keller Gordon, Sefton Michael V, Radisic Milica
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
Nat Mater. 2016 Jun;15(6):669-78. doi: 10.1038/nmat4570. Epub 2016 Mar 7.
We report the fabrication of a scaffold (hereafter referred to as AngioChip) that supports the assembly of parenchymal cells on a mechanically tunable matrix surrounding a perfusable, branched, three-dimensional microchannel network coated with endothelial cells. The design of AngioChip decouples the material choices for the engineered vessel network and for cell seeding in the parenchyma, enabling extensive remodelling while maintaining an open-vessel lumen. The incorporation of nanopores and micro-holes in the vessel walls enhances permeability, and permits intercellular crosstalk and extravasation of monocytes and endothelial cells on biomolecular stimulation. We also show that vascularized hepatic tissues and cardiac tissues engineered by using AngioChips process clinically relevant drugs delivered through the vasculature, and that millimetre-thick cardiac tissues can be engineered in a scalable manner. Moreover, we demonstrate that AngioChip cardiac tissues implanted with direct surgical anastomosis to the femoral vessels of rat hindlimbs establish immediate blood perfusion.
我们报告了一种支架（以下简称血管芯片）的制造方法，该支架能够支持实质细胞在围绕着灌注的、分支的、三维微通道网络的机械可调基质上组装，微通道网络表面涂覆有内皮细胞。血管芯片的设计将工程化血管网络和实质细胞接种的材料选择分离开来，在保持开放血管腔的同时实现广泛重塑。血管壁中纳米孔和微孔的加入提高了通透性，并允许在生物分子刺激下单核细胞和内皮细胞的细胞间串扰和外渗。我们还表明，使用血管芯片构建的血管化肝组织和心脏组织能够处理通过脉管系统递送的临床相关药物，并且毫米厚的心脏组织能够以可扩展的方式构建。此外，我们证明，通过直接手术吻合植入大鼠后肢股血管的血管芯片心脏组织能够立即建立血液灌注。
