Engineering Oral Tumor Microcirculation: Blood and lymphatic capillary network-enabled Human Oral Tumor Microenvironment Chips for Preclinical Research - ABSTRACT Engineering Oral Tumor Microcirculation: Engineering blood and lymphatic capillary network-enabled Human Oral Tumor Microenvironment Chips for Preclinical Research Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer with limited treatment options and poor survival rates, primarily due to our incomplete understanding of its tumor microenvironment (TME). Key processes such as angiogenesis, lymphangiogenesis, and vasculogenesis are pivotal to tumor growth, immune response, and metastasis but remain underexplored in OSCC research. Current tumor models lack the complexity required to mimic these vascular dynamics, impeding the study of tumor-endothelial crosstalk and the microcirculatory transport of immune cells, platelets, and therapeutic agents. To address this challenge, we propose the development of advanced tumor microenvironment chips (TME-chips) that incorporate perfusable blood and lymphatic capillary networks. These innovative systems, designed to recreate OSCC’s TME with unprecedented accuracy, will integrate 3D tumor spheroids and allow for simultaneous modeling of angiogenesis, lymphangiogenesis, and microcirculatory dynamics. Here, we aim (1) to engineer TME-chips with functional blood capillary networks to explore the roles of tumor-driven angiogenesis and therapeutic responses, and (2) to develop lymphatic capillary network-enabled TME-chips to investigate the mechanisms of tumor metastasis and lymphatic transport. By combining advanced microengineering with cutting-edge cancer biology, this project will provide a platform to unravel the complex interactions driving OSCC progression and resistance to therapies. The proposed research is significant in its potential to transform OSCC modeling, offering insights into vascularized tumor environments that were previously unattainable. By bridging critical knowledge gaps, these TME-chips will serve as powerful tools for preclinical drug testing, biomarker discovery, and the design of more effective therapeutic strategies, ultimately addressing an unmet need in OSCC research and patient care.
