Three-Dimensional Bioprinting-Enabled Organoids for Engineering the Tumor Microenvironment.
TL;DR
Three-dimensional bioprinting technology has emerged as a promising engineering tool for constructing TME-like models with controlled spatial architecture, tunable matrix properties, and programmable multicellular organization and practical directions for developing more physiologically relevant platforms for cancer research, drug screening, and precision oncology are outlined.
Abstract
The tumor microenvironment (TME) is a complex and dynamic system composed of immune cells, stromal cells, and extracellular matrix (ECM), whose composition and spatial architecture critically influence tumor initiation, progression, invasion, metastasis, and response to immunotherapy. However, traditional research models such as two-dimensional cell coculture, patient-derived xenograft models, and conventional patient-derived organoid (PDO) systems remain limited in simulating the complexity and physiological relevance of the TME. Three-dimensional (3D) bioprinting technology, with its precise spatial control capabilities and advantages in multicellular integration, has emerged as a promising engineering tool for constructing TME-like models with controlled spatial architecture, tunable matrix properties, and programmable multicellular organization. This review examines the principles and capabilities of major 3D bioprinting technologies (extrusion-based, droplet-based, photopolymerization-based) and evaluates their applications in reconstructing key TME features such as matrix remodeling, vascularization, immune cell integration, and drug response modeling with organoids. Importantly, we distinguish between bioprinted organoid-based systems and bioprinted tumor cell models, highlighting their differences in biological fidelity and translational relevance. In addition, challenges including limited integration of PDO, constraints in multicellular coculture, and insufficient long-term functional stability continue to restrict the physiological relevance of these models. Overall, this review provides an engineering-oriented perspective on the current state of bioprinted TME models and outlines practical directions for developing more physiologically relevant platforms for cancer research, drug screening, and precision oncology.