Integrating Additive and Traditional Manufacturing for Multiscale Bone Tissue Engineering Scaffolds.

Abstract

Additive manufacturing (AM) has emerged as a cutting-edge technology for fabricating biomimetic scaffolds with controllable architectures and compositional diversity, showing great promise in the fields of bone tissue engineering (BTE) and regenerative medicine. However, due to limitations in printing resolution and single-process capabilities, AM alone struggles to replicate the complex multiscale hierarchical structures inherent in native bone. Traditional fabrication techniques provide valuable complementary strategies to address these limitations. This review systematically summarizes recent advances in the construction of heterogeneous scaffolds from a multiscale design perspective, encompassing macro-, meso-, and microscale approaches. Emphasis is placed on the integration of major AM techniques-such as extrusion-based and light-based printing-with conventional methods including freeze-drying, gas foaming, and electrospinning. Particular attention is given to emerging in situ fabrication strategies, such as in situ foaming and mineralization, which enable spatially resolved and functionally graded architectures. Furthermore, this review explores pathways for constructing multiscale-integrated scaffolds and examines the current challenges and opportunities in clinical translation. Collectively, this work provides a comprehensive framework to guide the development of next-generation bone tissue scaffolds with enhanced biological performance and translational potential.