Artificial intelligence-empowered 4D bioprinting for craniomaxillofacial subunit reconstruction: a comprehensive review

Craniomaxillofacial subunit transplantation represents one of the most technically demanding reconstructive strategies for repairing anatomical subunit defects involving the cranium, mandible, maxilla, orbital cavity and nose. Conventional reconstructive approaches are hindered by inherent limitations in personalized anatomical matching, dynamic tissue adaptability, and long-term therapeutic efficacy. The integration of artificial intelligence (AI) and four-dimensional (4D) bioprinting has revolutionized craniomaxillofacial reconstructive surgery. This review summarizes state-of-the-art advances in AI-enabled 4D bioprinting for craniomaxillofacial subunit repair, covering core application scenarios including bone defect regeneration, facial soft tissue and cutaneous organ reconstruction, peripheral neural regeneration, and vascularized composite tissue fabrication. We elaborate the synergistic potential of AI and 4D bioprinting in craniomaxillofacial subunit reconstruction, and dissect critical bottlenecks including inadequate material performance, low precision of shape deformation programming, and limited clinical translatability of existing AI models. This work provides valuable insights for further translational research of AI-integrated 4D bioprinting in craniomaxillofacial subunit reconstruction.