Four-Dimensional Bioprinting: Current Developments and Applications in Bone Tissue Engineering

Abstract

Four-dimensional (4D) bioprinting, in which the concept of time is integrated with three-dimensional (3D) bioprinting as the fourth dimension, is widely proposed as the next-generation of tissue engineering technology as it presents the possibility of constructing complex, functional structures. 4D bioprinting can be used to fabricate dynamic 3D patterned biological architectures that change their shapes or functions under various stimuli by employing stimuli-responsive materials or novel 3D bioprinting strategies, providing unprecedented potential for bone tissue engineering. The shape memory properties of printed structures cater to the need for personal bone defect repair and biomimetic microenvironments that promote the osteogenic differentiation of stem cells. In this review, we introduce the application of different stimuli-responsive biomaterials in tissue engineering and a series of novel 4D bioprinting strategies based on functional transformation of printed structures through the establishment of biomimetic constructs. Furthermore, we discuss the application of 4D bioprinting in bone tissue engineering, as well as future challenges and perspectives.