Deep Learning Network‐Tailored Microenvironment Matching of 4D Bioprinting Bioactive Scaffolds for Bone Regeneration

Xiongjie Liang, Yuechi Zhang, Weifeng Hu, Shiyan Lv, Fan Jia, Yan Zhang, Feng Wu, Changjiang Yang, Guanqi Zhen, Jinglong Yan, Xu Cui, Wei Zhao, Guanghua Chen

ABSTRACT Pathological microenvironments linked to aging, trauma, malignancies, and metabolic disorders significantly hinder bone fractures and frequently result in fracture nonunion, posing substantial worldwide clinical difficulties. Widely prevalent therapies encounter difficulties in addressing diverse anatomical defects and variable illness conditions due to their inflexible designs and limitations in empirical optimization. Efficient strategies are critical to restore mechanics, improve pathological microenvironments, enhance neovascularization, and adapt to anatomical defects and clinical conditions. Deep learning networks (DLN) excel at analyzing extensive nonlinear relationships, enabling predictions of biomaterial‑biological interactions, hence accelerating biomaterial development. This study presents a synergistic DLN and 4D printing approach to fabricate a microenvironment‐adaptive bioactive scaffold (MABS) for enhanced osteogenesis and angiogenesis. The scaffold integrates bioactive glass and a shape‐memory PgP matrix, with a multilayer perceptron (MLP) neural network optimizing its design via nonlinear parameter‐performance analysis. In vivo investigations revealed that the DLN‐optimized scaffold enhanced shape‐morphing adaptability and promoted the formation of dense bone tissue and vascular networks. This paradigm shift—employing DLN to integrate 4D printing dynamics, degradation kinetics, and multi‐scale biological responses—transforms bone implants from static entities to dynamically adaptive systems, offering a scalable, intelligent framework for precise bone repair that rectifies the deficiencies of current strategies.