Gastric Cancer Models Developed via GelMA 3D Bioprinting Accurately Mimic Cancer Hallmarks, Tumor Microenvironment Features, and Drug Responses

Abstract

Current in vitro models for gastric cancer research, such as 2D cell cultures and organoid systems, often fail to replicate the complex extracellular matrix (ECM) found in vivo. For the first time, this study utilizes a gelatin methacryloyl (GelMA) hydrogel, a biomimetic ECM-like material, in 3D bioprinting to construct a physiologically relevant gastric cancer model. GelMA's tunable mechanical properties allow for the precise manipulation of cellular behavior within physiological ranges. Genetic and phenotypic analyses indicate that the 3D bioprinted GelMA (3Db) model accurately mimics the clinical tumor characteristics and reproduces key cancer hallmarks, such as cell proliferation, invasion, migration, angiogenesis, and the Warburg effect. Comparisons of gene expression and drug responses between the 3Db model and patient-derived xenograft models, both constructed from primary gastric cancer cells, validate the model's clinical relevance. The ability of the 3Db model to closely simulate in vivo conditions highlights its crucial role in identifying treatment targets and predicting patient-specific responses, showcasing its potential in high-throughput drug screening and clinical applications. This study is the first to report the pivotal role of GelMA-based 3D bioprinting in advancing gastric cancer research and regenerative medicine.