Vascularization remains a long-standing challenge in engineering complex tissues. Particularly needed is recapitulating 3D vascular features, including continuous geometries with defined diameter, curvature, and torsion. Here, we developed a spiral microvessel model that allows precise control of curvature and torsion and supports homogeneous tissue perfusion at the centimeter scale. Using this system, we showed proof-of-principle modeling of tumor progression and engineered cardiac tissue vascularization. We demonstrated that 3D curvature induced rotation and mixing under laminar flow, leading to unique phenotypic and transcriptional changes in endothelial cells (ECs). Bulk and single-cell RNA-seq identified specific EC gene clusters in spiral microvessels. These mark a proinflammatory phenotype associated with vascular development and remodeling, and a unique cell cluster expressing genes regulating vascular stability and development. Our results shed light on the role of heterogeneous vascular structures in differential development and pathogenesis and provide previously unavailable tools to potentially improve tissue vascularization and regeneration.

血管化仍然是工程复杂组织的长期挑战。特别需要概括 3D 血管特征，包括具有定义直径、曲率和扭转的连续几何形状。在这里，我们开发了一种螺旋微血管模型，可以精确控制曲率和扭转，并支持厘米级的均匀组织灌注。使用该系统，我们展示了肿瘤进展和工程心脏组织血管化的原理验证模型。我们证明了 3D 曲率在层流下诱导旋转和混合，导致内皮细胞 (EC) 发生独特的表型和转录变化。散装和单细胞 RNA-seq 鉴定了螺旋微血管中的特定 EC 基因簇。这些标志着与血管发育和重塑相关的促炎表型，和一个独特的细胞簇，表达调节血管稳定性和发育的基因。我们的研究结果揭示了异质血管结构在差异发育和发病机制中的作用，并提供了以前无法获得的工具来潜在地改善组织血管化和再生。