Multitechnological integration advances musculoskeletal regeneration: synergistic progress of organoids, 3D/4D bioprinting, single-cell omics and artificial intelligence

Regenerative repair of injuries and degenerative diseases in the musculoskeletal system remains a paramount clinical challenge, as conventional single-modal technologies fail to recapitulate the intricate structural and functional complexity of native musculoskeletal tissues. In recent years, the rapid evolution of cutting-edge technologies-including organoids, 3D/4D bioprinting, single-cell omics and artificial intelligence (AI)-has unlocked novel opportunities for addressing this longstanding issue. This review aims to systematically elucidate how the integration of these four core technologies drives progress in musculoskeletal regeneration research. By exploring the intrinsic methodological details of each technology and their underlying synergistic mechanisms, we summarize the latest advances in multitechnological integration for fabricating highly biomimetic <i>in vitro</i> models, enabling precise and dynamic fabrication of tissue-engineered constructs, deciphering cellular heterogeneity during tissue development and repair at high resolution, and optimizing data-driven personalized regenerative strategies. We further explicitly distinguish the <i>in vitro</i> and <i>in vivo</i> applications of each technology with representative experimental evidence and translational implications, and provide comprehensive tabular summaries of state-of-the-art research over the past 5 years. Furthermore, we prospect the future development directions and critical challenges facing this interdisciplinary field.