Recent Advances in 3D Printing of Smart Scaffolds for Bone Tissue Engineering and Regeneration

The repair and functional reconstruction of bone defects resulting from severe trauma, surgical resection, degenerative disease, and congenital malformation pose significant clinical challenges. Bone tissue engineering (BTE) holds immense potential in treating these severe bone defects, without incurring prevalent complications associated with conventional autologous or allogeneic bone grafts. 3D printing technology enables control over architectural structures at multiple length scales and has been extensively employed to process biomimetic scaffolds for BTE. In contrast to inert and functional bone grafts, next-generation smart scaffolds possess a remarkable ability to mimic the dynamic nature of native extracellular matrix (ECM), thereby facilitating bone repair and regeneration. Additionally, they can generate tailored and controllable therapeutic effects, such as antibacterial or antitumor properties, in response to exogenous and/or endogenous stimuli. This review provides a comprehensive assessment of the progress of 3D-printed smart scaffolds for BTE applications. It begins with an introduction to bone physiology, followed by an overview of 3D printing technologies utilized for smart scaffolds. Notable advances in various stimuli-responsive strategies, therapeutic efficacy, and applications of 3D-printed smart scaffolds are discussed. Finally, the review highlights the existing challenges in the development and clinical implementation of smart scaffolds, as well as emerging technologies in this field.