Advances in 3D Vascularized Tumor-on-a-Chip Technology.

Tumors disrupt the normal homeostasis of human body as they proliferate in abnormal speed. For constant proliferation, tumors recruit new blood vessels transporting nutrients and oxygen. Immune system simultaneously recruits lymphatic vessels to induce the death of tumor cells. Hence, understanding tumor dynamics are important to developing anti-cancer therapies. Tumor-on-a-chip technology can be applied to identify the structural and functional units of tumors and tumor microenvironments with high reproducibility and reliability, monitoring the development and pathophysiology of tumors, and predicting drug effectiveness. Herein, we explore the ability of tumor-on-a-chip technology to mimic angiogenic and lymphangiogenic tumor microenvironments of organs. Microfluidic systems allow elaborate manipulation of the development and status of cancer. Therefore, they can be used to validate the effects of various drug combinations, specify them, and assess the factors that influence cancer treatment. We discuss the mechanisms of action of several drugs for cancer treatment in terms of tumor growth and progression involving angiogenesis and lymphangiogenesis. Moreover, we present future applications of emerging tumor-on-a-chip technology for drug development and cancer therapy.

Vascularized tissue on mesh-assisted platform (VT-MAP): a novel approach for diverse organoid size culture and tailored cancer drug response analysis.

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.