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Cartilage tissue engineering is a promising approach for repairing articular cartilage defects and requires proper scaffolds and necessary growth factors. Herein, tanshinone IIA (TAN) delivery silk fibroin scaffolds were prepared for efficient cartilage defect repair by bioactivities of TAN. By incubating with the TAN delivery silk fibroin scaffold, the transcription of the chondrocytic activity-related genes was enhanced in chondrocytes, and it also can inhibit cell apoptosis and reduce the oxidative stress by regulating the transcription of related genes, indicating that these scaffolds may promote cartilage regeneration. TAN10 delivery silk fibroin scaffolds, in which the concentration of TAN is 10 μg/mL, significantly promotes chondrocytes to generate the cartilage-specific extracellular matrix and tissue both in vitro and in vivo, compared with silk fibroin scaffolds. By treating rabbit articular cartilage defects with TAN10 delivery silk fibroin scaffolds, cartilage defects were filled with hyaline-cartilage-like tissue that integrated with the surrounding cartilage perfectly and displayed strong mechanical properties and higher extracellular matrix content. Hence, TAN facilitates cartilage regeneration, and TAN delivery silk fibroin scaffolds can be potentially applied in the clinics treating cartilage defects in the future.

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In vitro three‐dimensional (3D) cartilage regeneration is a promising strategy for repair of cartilage defects. However, inferior mechanical strength and tissue homogeneity greatly restricted its clinical translation. Simulation of mechanical stress through a bioreactor is an important approach for improving in vitro cartilage regeneration. The current study developed a hydrostatic pressure (HP) bioreactor based on a novel pressure‐transmitting mode achieved by slight deformation of a flexible membrane in a completely sealed stainless steel device. The newly developed bioreactor efficiently avoided the potential risks of previously reported pressure‐transmitting modes and simultaneously addressed a series of important issues, such as pressure scopes, culture chamber sizes, sealability, contamination control, and CO2 balance. The whole bioreactor system realized stable long‐term (8 weeks) culture under high HP (5–10 MPa) without the problems of medium leakage and contamination. Furthermore, the results of in vitro 3D tissue culture based on a cartilage regeneration model revealed that HP provided by the newly developed bioreactor efficiently promoted in vitro 3D cartilage formation by improving its mechanical strength, thickness, and homogeneity. Detailed analysis in cell proliferation, cartilage matrix production, and cross‐linking level of collagen macromolecules, as well as density and alignment of collagen fibers, further revealed the possible mechanisms that HP regulated in vitro cartilage regeneration. The current study provided a highly efficient and stable bioreactor system for improving in vitro 3D cartilage regeneration and thus will help to accelerate its clinical translation. Stem Cells Translational Medicine 2017;6:982–991

The transplantation of tissue-engineered scaffolds with stem cells is a promising therapeutic approach for bone defect repair. To improve the therapeutic efficacy of this approach, in this study, a novel biofunctional live tissue-engineered bone-like graft was designed and constructed using a fibrin scaffold loaded with TG2 gene-modified ectomesenchymal stem cells (TG2-EMSCs) derived from nasal respiratory mucosa for bone defect repair. Autocalcification of the cell-free fibrin gel in osteogenic medium with additional alkaline phosphatase (ALP) and the osteogenic differentiation of TG2-EMSCs on the fibrin scaffold were assessed in vitro. The results indicated that the cell-free fibrin gel could autocalcify in the osteogenic medium with ALP and that the overexpression of TG2 by TG2-EMSCs could promote the osteogenic differentiation of these stem cells in the fibrin scaffold. Moreover, TG2 could enhance the deposition of extracellular matrix proteins in the fibrin scaffold, followed by calcification of the bone matrix in vitro. After transplantation into critical-sized cranial defects in rats, the functional tissue-engineered bone-like grafts improved bone regeneration. These results indicate that this tissue-engineered bone-like graft could improve the process of bone defect repair.