A rational framework for 3D bioprinting of organoids: From assembly mechanisms and material properties to functional outcomes

Organoids hold great promise for modeling development, disease, and patient-specific therapy, but their translation is limited by poor vascularization, lack of immune and neural components, low reproducibility, and difficulties in scale-up. 3D bioprinting can address these bottlenecks by enabling digitally guided, spatially precise deposition of bioinks to construct multiscale architectures and perfusable channel networks, yet matching printing principles with material systems remains a central challenge. Unlike existing reviews that focus on isolated technologies or materials, this review introduces a cohesive paradigm that systematically links assembly mechanisms, material properties, and organoid functions along a mechanism–material–function axis. Its core breakthrough shifts the field from empirical guesswork to on-demand engineered design. We analyzed physicochemical mechanisms, such as ionic crosslinking, hydrophobic interactions, dynamic covalent bonding, and photoinitiated polymerization, and mapped them to tunable metrics, including modulus, degradation kinetics, mass-transport capacity, and bioactive delivery. Based on this mapping, we developed a full-chain decision framework for technology selection, material design, and process-parameter optimization, and proposed a predictive, reproducible formulation strategy. By transforming organoid fabrication from an empirical practice into an engineering discipline, this framework enables predictable and scalable organoid fabrication for regenerative medicine, drug discovery, and disease modeling applications through standardized process-parameter optimization and material recipe design.