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Recent advancements in tissue engineering have demonstrated a great potential for the fabrication of three-dimensional tissue structures such as cartilage and bone. However, achieving structural integrity between different tissues and fabricating tissue interfaces are still great challenges. In this study, an in situ crosslinked hybrid, multi-material three-dimensional (3D) bioprinting approach was used for the fabrication of hydrogel structures based on an aspiration-extrusion microcapillary method. Different cell-laden hydrogels were aspirated in the same microcapillary glass and deposited in the desired geometrical and volumetric arrangement directly from a computer model. Alginate and carboxymethyl cellulose (CMC) were modified with tyramine to enhance cell bioactivity and mechanical properties of human bone marrow Mesenchymal Stem Cells (hBMSC)-laden bioinks. Hydrogels were prepared for extrusion by gelling in microcapillary glass utilizing an in situ crosslink approach with ruthenium (Ru) and sodium persulfate (SPS) photo-initiating mechanisms under visible light. The developed bioinks were then bioprinted in precise gradient composition for cartilage-bone tissue interface using microcapillary bioprinting technique. The biofabricated constructs were co-cultured in chondrogenic/osteogenic culture media for three weeks. After cell viability and morphology evaluations of the bioprinted structures, biochemical and histological analyses, and a gene expression analysis for the bioprinted structure were carried out. Analysis of cartilage and bone formation based on cell alignment and histological evaluation indicated that mechanical cues in conjunction with chemical cues successfully induced MSC differentiation into chondrogenic and osteogenic tissues with a controlled interface.

It is a large clinical challenge to repair critical-size bone defects, and vascularization in the early stage is of vital importance in bone regeneration. In recent years, 3D-printed bioceramic is a kind of common bioactive scaffold for repairing bone defects. However, conventional 3D-printed bioceramic scaffolds consist of stacked solid struts with low porosity, which limits the ability of angiogenesis and bone regeneration. The hollow tube structure can induce endothelial cells to build the vascular system. In this study, β-tricalcium phosphate (β-TCP) bioceramic scaffolds containing the hollow tube structure were prepared with digital light processing-based 3D printing strategy. The physicochemical properties and osteogenic activities of prepared scaffolds could be precisely controlled by adjusting the parameters of hollow tubes. Compared with solid bioceramic scaffolds, such scaffolds could significantly improve the proliferation and attachment activity of rabbit bone mesenchymal stem cells in vitro, and facilitate early angiogenesis and subsequent osteogenesis in vivo. Therefore, β-TCP bioceramic scaffolds with the hollow tube structure possess great potential application for the treatment of critical-size bone defects.

Elimination of residual osteosarcoma cells and repair of bone defects remain major challenges for osteosarcoma in clinic. To address this problem, it is required that multifunctional therapeutic platform possess high tumor-killing efficiency and simultaneous bone regeneration capabilities. In this work, an intelligent therapeutic platform was developed to achieve highly-efficient tumor therapy and simultaneous significantly improved bone defect repairing ability, which was realized byin situgrowing ferromagnetic Fe3S4layers with tuned microstructures on the surface of 3D-printed akermanite bioceramic scaffolds via hydrothermal method. The Fe3S4layers exploited magnetic thermal energy to enhance chemodynamic treatment, thus achieving a synergistic effect between magnetothermal and chemodynamic therapy on the elimination of residual tumor cells. Moreover, the micro-structured surface of the 3D-printed bioceramic scaffolds further enhanced the osteogenic activityin vitroand accelerated the bone regenerationin vivo. The scaffolds with multi-mode tumor-killing and bone repairing capabilities indicated that such a therapeutic platform is applicable for a stepwise treatment strategy of osteosarcoma and provides inspiration for the design of multifunctional biomaterials.

Bacterial infection poses a significant risk with the wide application of bone graft materials. Designing bone grafts with good antibacterial performance and excellent bone-forming activity is of particular significance for bone tissue engineering. In our study, a 3D printing method was used to prepare β-tricalcium phosphate (β-TCP) bioceramic scaffolds. Silver (Ag) nanoparticles were uniformly dispersed on graphene oxide (GO) to form a homogeneous nanocomposite (named Ag@GO) with different Ag-to-graphene oxide mass ratios, with this being synthesized via the liquid chemical reduction approach. Ag@GO nanocomposites were successfully modified on the β-TCP scaffolds by a simple soaking method to achieve bifunctional biomaterials with antibacterial and osteogenic activity. The prepared scaffolds possessed a connected network with triangle pore morphology and the surfaces of the β-TCP scaffolds were uniformly modified by the Ag@GO nanocomposite layers. The Ag content in the scaffolds was controlled by changing the coating times and concentration of the Ag@GO nanocomposites. The antibacterial activity of the scaffolds was assessed with Gram-negative bacteria (Escherichia coli, E. coli). The results demonstrated that the scaffolds with Ag@GO nanocomposites presented excellent antibacterial activity. In addition, the scaffolds coated with Ag@GO nanocomposites conspicuously accelerated the osteogenic differentiation of rabbit bone marrow stromal cells by improving their alkaline phosphatase activity and bone-related gene expression (osteopontin, runt-related transcription factor 2, osteocalcin and bone sialoprotein). This study demonstrates that bifunctional scaffolds with a combination of antibacterial and osteogenic activity can be achieved for the reconstruction of large-bone defects while preventing or treating infections.

Silicate bioceramics, as a new family of biomaterials, have received significant attention in their application to hard tissue regeneration. Some silicate bioceramics have shown excellent apatite mineralization in simulated body fluids and their ionic products have been shown to enhance the proliferation, osteogenic differentiation and gene expression of stem cells. In this paper, we review the advances in the research of silicate system bioceramics, including preparation methods, mechanical strength, apatite mineralization, dissolution and in vitro and in vivo biological properties. The biological properties and the corresponding mechanism have been highlighted. A look forward to the application of silicate bioceramics to bone regeneration is further suggested.