dECM bioinks for 3D bioprinted tumor models: Advances, challenges, and drug screening

The pressing need for high-fidelity in vitro tumor models that accurately recapitulate the native tumor microenvironment (TME) remains a critical bottleneck in cancer drug discovery and personalized therapy. Decellularized extracellular matrix (dECM) has emerged as a superior biomaterial, attributed to its retained bioactivity, low immunogenicity, and tunable biodegradability. This review examines the integration of 3D bioprinting with dECM for tumor modeling, with particular emphasis on dECM sourcing, processing methodologies, and biofabrication parameters-and their collective influence on model fidelity. We systematically analyze the current bioprinting modalities, critically assess the obstacles in dECM preparation and functionalization that compromise printability and biological performance, and elucidate how these determinants shape tumor model construction. Importantly, we identify persistent technical challenges, including the inherent trade-off between printability and bioactivity, the difficulty of replicating patient-specific heterogeneity, and the lack of standardized characterization protocols, all of which collectively constrain the predictive capacity of these platforms. Finally, we outline future directions, highlighting the incorporation of patient-derived dECM, advanced multimaterial printing, and artificial intelligence-driven design optimization as pivotal strategies for developing clinically actionable and predictive preclinical systems capable of effectively translating in vitro findings into in vivo outcomes.