The Next Phase of 3D Bioprinting: AI-Native Systems—A Narrative Review

Three-dimensional (3D) bioprinting has reached a complexity limit where empirical, parameter-by-parameter optimization no longer scales. The dominant mode of artificial intelligence (AI) integration remains AI-augmented, where AI is treated as an analytical addition to a conventional pipeline. We argue that the field is approaching a discontinuous transition towards AI-native bioprinting, in which AI represents the operational layer of system intelligence, not an ancillary tool. A systematic analysis of 365 publications on the intersection of bioprinting and AI (2015–2026), performed through 18 queries organized by the four search axes of the PubMed database, shows that the intersection grew 136 times during the decade, with an acceleration of 3.16 times only between 2024 and 2025. Mapping the publications to the six functional domains reveals a marked asymmetry: clinical translation counts 154 papers, while cell viability prediction—the biological foundation that every closed-loop system requires—counts only three. We define AI-native bioprinting as a system architecture that combines continuous learning, multi-modal sensing fused through visual, mechanical and biological signals, and biologically closed control loops. We present a conceptual shift from printing accuracy to biological intelligence as a success criterion. The transition requires open datasets, consensus biological metrics, inter-laboratory validation, and early regulatory engagement.