This study presents the vascularized tissue on mesh-assisted platform (VT-MAP), a novel microfluidic in vitro model that uses an open microfluidic principle for cultivating vascularized organoids. Addressing the gap in 3D high-throughput platforms for drug response analysis, the VT-MAP can host tumor clusters of various sizes, allowing for precise, size-dependent drug interaction assessments. Key features include capability for forming versatile co-culture conditions (EC, fibroblasts and colon cancer organoids) that enhance tumor organoid viability and a perfusable vessel network that ensures efficient drug delivery and maintenance of organoid health. The VT-MAP enables the culture and analysis of organoids across a diverse size spectrum, from tens of microns to several millimeters. The VT-MAP addresses the inconsistencies in traditional organoid testing related to organoid size, which significantly impacts drug response and viability. Its ability to handle various organoid sizes leads to results that more accurately reflect patient-derived xenograft (PDX) models and differ markedly from traditional in vitro well plate-based methods. We introduce a novel image analysis algorithm that allows for quantitative analysis of organoid size-dependent drug responses, marking a significant step forward in replicating PDX models. The PDX sample from a positive responder exhibited a significant reduction in cell viability across all organoid sizes when exposed to chemotherapeutic agents (5-FU, oxaliplatin, and irinotecan), as expected for cytotoxic drugs. In sharp contrast, PDX samples of a negative responder showed little to no change in viability in smaller clusters and only a slight reduction in larger clusters. This differential response, accurately replicated in the VT-MAP, underscores its ability to generate data that align with PDX models and in vivo findings. Its capacity to handle various organoid sizes leads to results that more accurately reflect PDX models and differ markedly from traditional in vitro methods. The platform's distinct advantage lies in demonstrating how organoid size can critically influence drug response, revealing insights into cancer biology previously unattainable with conventional techniques.

中文翻译：

---

网格辅助平台上的血管化组织（VT-MAP）：一种用于不同类器官大小培养和定制癌症药物反应分析的新方法

本研究提出了网格辅助平台上的血管化组织（VT-MAP），这是一种新型微流体体外模型，采用开放式微流体原理来培养血管化类器官。 VT-MAP 弥补了药物反应分析 3D 高通量平台的空白，可以容纳各种大小的肿瘤簇，从而可以进行精确的、大小依赖的药物相互作用评估。主要功能包括形成多功能共培养条件（EC、成纤维细胞和结肠癌类器官）的能力，以增强肿瘤类器官的活力，以及可灌注的血管网络，以确保有效的药物输送和维持类器官的健康。 VT-MAP 能够培养和分析各种尺寸范围（从几十微米到几毫米）的类器官。 VT-MAP 解决了传统类器官测试中与类器官大小相关的不一致问题，这显着影响了药物反应和活力。其处理各种类器官大小的能力导致结果更准确地反映患者来源的异种移植（PDX）模型，并且与传统的基于体外孔板的方法显着不同。我们引入了一种新颖的图像分析算法，可以对类器官大小依赖性药物反应进行定量分析，这标志着在复制 PDX 模型方面向前迈出了重要一步。当暴露于化疗药物（5-FU、奥沙利铂和伊立替康）时，阳性反应者的 PDX 样本表现出所有类器官大小的细胞活力显着降低，正如细胞毒性药物所预期的那样。与此形成鲜明对比的是，阴性反应者的 PDX 样本显示，较小簇中的活力几乎没有变化，而较大簇中的活力仅略有下降。这种差异反应在 VT-MAP 中准确复制，强调了其生成与 PDX 模型和体内研究结果一致的数据的能力。它能够处理各种大小的类器官，从而获得更准确地反映 PDX 模型的结果，并且与传统的体外方法显着不同。该平台的独特优势在于展示类器官大小如何对药物反应产生关键影响，揭示以前用传统技术无法实现的对癌症生物学的见解。