Microphysiological Systems Integrating Bioprinting, Organoids, Organ-on-a-Chip, and AI: Next Generation Platforms for...

Microphysiological systems (MPS) have emerged as transformative in vitro platforms to address the long-standing bottlenecks of conventional preclinical models, including poor physiological relevance inherent to 2D cultures, as well as species incompatibility and ethical constraints associated with animal models, thereby improving clinical predictability and redefining modern pharmaceutical development. This review highlights the innovative convergence of bioprinting, organoids, organ-on-a-chip (OoC), and artificial intelligence (AI) as a next-generation MPS framework, enabling precision reconstruction of human tissue microenvironments with unprecedented fidelity. Bioprinting delivers spatially defined 3D architectures; organoids recapitulate organ-specific heterogeneity; OoC integrates dynamic physiological cues; and AI enables intelligent fabrication optimization, real-time monitoring, and predictive drug-response modeling. Their synergistic integration overcomes the inherent limitations of single-technology systems. We emphasize state-of-the-art MPS applications in disease-drug screening, and toxicological assessment across tissues and multiorgan crosstalk models, underscoring their paradigm-shifting potential. Remaining challenges, such as long-term functional maturation, vascularization complexity, and standardized validation, and future directions, including multi-cue integration, modular scalability, and AI-driven in vitro-in vivo correlation, are concisely outlined. This interdisciplinary synthesis establishes MPS as a cornerstone technology to accelerate pharmaceutical innovation, reduce reliance on animal models, and advance precision medicine toward clinical translation, thereby filling a critical gap in current biomedical research.