Abstract
Vascularization in bone tissues is essential for the distribution of nutrients and oxygen, as well as the removal of waste products. Fabrication of tissue-engineered bone constructs with functional vascular networks has great potential for biomimicking nature bone tissue in vitro and enhancing bone regeneration in vivo. Over the past decades, many approaches have been applied to fabricate biomimetic vascularized tissue-engineered bone constructs. However, traditional tissue-engineered methods based on seeding cells into scaffolds are unable to control the spatial architecture and the encapsulated cell distribution precisely, which posed a significant challenge in constructing complex vascularized bone tissues with precise biomimetic properties. In recent years, as a pioneering technology, three-dimensional (3D) bioprinting technology has been applied to fabricate multiscale, biomimetic, multi-cellular tissues with a highly complex tissue microenvironment through layer-by-layer printing. This review discussed the application of 3D bioprinting technology in the vascularized tissue-engineered bone fabrication, where the current status and unique challenges were critically reviewed. Furthermore, the mechanisms of vascular formation, the process of 3D bioprinting, and the current development of bioink properties were also discussed.
Highlights
Treatment of large bone defects resulting from cancer, trauma, infection, congenital malformation, or surgical resection is a challenge for clinical doctors [1]
Colosi et al utilized this combined bioprinting technique to fabricate the tissue-engineered constructs with human umbilical vein endothelial cell–lined vasculature by depositing different bioinks using a blend of alginate and gelatin methacrylate (GelMA) [107]
Zhou et al utilized 3D bioprinting technology to constuct a 3D bioprinted tissue-engineered bone construct that facilitates the integration of mesenchymal stem cells (MSCs), breast cancer (BrCa) cells, and osteoblasts [186]
Summary
Treatment of large bone defects resulting from cancer, trauma, infection, congenital malformation, or surgical resection is a challenge for clinical doctors [1]. Traditional tissue-engineered methods based on seeding cells into the scaffold could not precisely control the inner structure, cell distribution, and exocellular microenvironment to meet the biomechanical functions and metabolic requirement of bone tissue [12]. Compared to conventional scaffold-based approaches, 3D bioprinting technology could precisely control complex 3D architecture, multiple compositions, and spatial distributions [13]. Both 3D printing and 3D bioprinting could utilize the layer-by-layer manner to fabricate 3D anatomically shaped constructs from a computer-aided design. 3D bioprinting technologies involve the utilization of cell-laden bioinks and other bioactive molecules to fabricate biomimetic tissue constructs during the printing process, while. The mechanisms of vascular formation, the process of 3D bioprinting, and the current development of bioink properties were discussed
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