Advances and challenges in 3D bioprinting of bone organoids: Materials, techniques, and functionalization strategies

The use of 3D bioprinting to construct bone organoids is of great interest in the field of bone tissue engineering due to its potential to replicate complex structures for research and regenerative medicine. 3D bioprinting enables the creation of precise, three-dimensional structures by depositing bioinks layer by layer based on digital models. However, challenges remain in achieving functional bone organoids, especially in the design of bioinks, vascularization, and maintaining cell viability. To address these issues, various printing techniques have been explored, such as extrusion, inkjet, light-curing, and microfluidic printing, but further advances are needed to improve the quality and functionality of printed bone organoids. This review assesses the current state of research on the application of 3D bioprinting techniques for the construction of bone organoids, focusing on the selection of bioinks, scaffold materials, and the role of cells and growth factors. Despite the progress made, significant challenges remain in optimizing the mechanical properties of bioinks, enhancing vascularization, and mimicking the dynamic physiological environment of bone tissue. The main objective of this study is to explore the technical challenges and opportunities in the construction of functional bone organoids through 3D bioprinting, with the aim of providing insights into future directions for overcoming these obstacles and improving bone tissue regeneration applications.