Acute injury of the articular cartilage can lead to chronic disabling conditions, because of its limited self-repair capability. Implantation of stem cells with chondrogenic differentiation potential at the injury sites...

With the development of regenerative medicine, tissue repair at the molecular, cellular, tissue, and organ level has seen continuous improvements over traditional techniques. As the core of tissue repair, seed...

Either osteoarthritis or sports-related injuries can lead to cartilage defects, whereas both chondrocyte self-renewal and conventional treatments face limitations. In cartilage regenerative medicine, growth factors are commonly used to induce chondrogenic differentiation of stem cells. However, application of growth factors is confined by some drawbacks. Emerging small molecules are regarded as an alternative for cartilage regeneration. A recently discovered small-molecule compound, kartogenin (KGN), has been proven to be a chondrogenic and chondroprotective agent and is more effective in inducing cartilage regeneration when compared with growth factors. KGN has been processed and applied in many forms, such as in intra-articular injection, in collaboration with growth factors, in incorporation in drug delivery systems, and in combination with scaffolds. Fortunately, progress has been achieved in KGN applications. The current review discusses the recent advances in KGN for cartilage regeneration and thus presents new concepts in cartilage repair in clinical settings.

A body of evidence has indicated that microRNAs (miRNAs) may have significant roles in cancer. Aberrant expression of miRNAs has frequently been observed in various human malignancies, including osteosarcoma (OS). However, the roles of miRNAs in OS remain poorly understood. In the present study, high-throughput deep sequencing was performed to screen for deregulated miRNAs in OS. Screening identified 310 miRNAs which were significantly overexpressed and 41 miRNAs which were significantly downregulated (>2-fold) in OS samples, compared with adjacent non-tumor bone tissues. Among these miRNAs, miR-33a-5p was notably downregulated. TaqMan reverse transcription-polymerase chain reaction analysis further verified that miR-33a-5p expression was significantly reduced in a large cohort of human OS samples. Enhancing miR-33a-5p expression via transfection with miR-33a-5p precursor significantly inhibited OS cell growth, suggesting potential antitumor properties of miR-33a-5p. The results of the present study provide novel insights into the miRNAs involved in OS, and suggest that miR-33a-5p may function as a tumor suppressor in OS. Therefore, miR-33a-5p may be able to serve as a diagnostic and therapeutic target for OS treatment.

Three-dimensional (3D) bioprinting is an emerging technology based on 3D digital imaging technology and multi-level continuous printing. The precise positioning of biological materials, seed cells, and biological factors, known as “additive biomanufacturing”, can provide personalized therapy strategies in regenerative medicine. Over the last two decades, 3D bioprinting hydrogels have significantly advanced the field of cartilage and bone tissue engineering. This article reviews the development of 3D bioprinting and its application in cartilage tissue engineering, followed by a discussion of the current challenges and prospects for 3D bioprinting. This review presents foundational information on the future optimization of the design and manufacturing process of 3D additive biomanufacturing.

Scaffolds play an important role in tissue engineering and their structure and biocompatibility have great influence on cell behaviors. In this study, poly(l-lactide-co-ε-caprolactone) (PLCL) scaffolds were printed by a 3D printing technology, low-temperature deposition manufacturing (LDM), and then PLCL scaffolds were treated by alkali and coated with collagen type I (COLI). The scaffolds were characterized by scanning electron microscopy (SEM), porosity test, mechanical test, and infrared spectroscopy. The prepared PLCL and PLCL-COLI scaffolds had three-dimensional (3D) porous structure and they not only have macropores but also have micropores in the deposited lines. Although the mechanical property of PLCL-COLI was slightly lower than that of PLCL scaffold, the hydrophilicity of PLCL-COLI was significantly enhanced. Rabbit articular chondrocytes were extracted and were identified as chondrocytes by toluidine blue staining. To study the biocompatibility, the chondrocytes were seeded on scaffolds for 1, 3, 5, 7, and 10 days. MTT assay showed that the proliferation of chondrocytes on PLCL-COLI scaffold was better than that on PLCL scaffold. And the morphology of cells on PLCL-COLI after 1-day culture was much better than that on PLCL. This 3D-printed PLCL scaffold coated with COLI shows a great potential application in tissue engineering.

This study was conducted to investigate the effect of magnetic nanoparticle composite scaffold under a pulsed electromagnetic field on bone marrow mesenchymal stem cells (BMSCs), which was achieved by examining the biological behaviors of cell adhesion, proliferation and differentiation on the surface of the scaffolds. This may provide some experimental evidence for the use of magnetic nanoparticles in medical application. The magnetic nanoparticle composite scaffolds were evaluated and characterized by the following indexes: the cell proliferation was detected by the CCK-8 method, the alkaline phosphatase (ALP) activity was examined by a detection kit, and the expression of type I collagen and osteocalcin gene were evaluated by RT-PCR. The CCK-8 test showed that there was no significant difference in Group A (BMSCs-seeded magnetic scaffolds under the electromagnetic field), B (BMSCs-seeded magnetic scaffolds) and C (BMSCs cultured alone) (P > 0.05). The value for the ALP activity in Group A was higher than the other two groups. In addition, the RT-PCR results showed that the expression of type I collagen gene in Group A was enhanced (P < 0.05), suggesting that the magnetic nanoparticles combined with the pulsed electromagnetic field had a positive effect on the osteogenic differentiation of BMSCs. However, the expression of osteocalcin was not significantly different in three groups (P > 0.05). To conclude, magnetic nanoparticles may induce the osteogenic differentiation with the action of the pulsed electromagnetic field.

Pulsed electromagnetic field therapy, or pulsed signal therapy, has shown efficacy in treating many illnesses, including knee osteoarthritis. Although the mechanism is not fully understood, magnetic therapy is broadly welcomed because of its safe and noninvasive nature. At the cellular and molecular level, remote control of the cell fate by the magnetic field also has profound applications in both basic science and translational research. Here we demonstrate the use of pulsed electromagnetic field, one of the most benign and noninvasive extracellular cues, as a novel method to control specific chondrogenic differentiation of mesenchymal stem cells (MSCs). Chondrogenesis of transplanted MSCs inside the joint is considered one of the future therapies to rebuild the damaged cartilage. Here we show that pulsed electromagnetic field promotes chondrogenic differentiation of MSCs, and such a promoting effect can be drastically enhanced by the combined use of a magnetic hydrogel as the cell growth matrix. The magnetic hydrogel, synthesized by chemical cross-linking of gelatin and β-cyclodextrin and by embedding Fe3O4 magnetic nanoparticles in the hydrogel network, supports adhesion, growth, and proliferation of MSCs. Pulsed electromagnetic field boosts chondrogenesis of MSCs grown on the magnetic hydrogel, manifested by enhanced toluidine blue staining; higher expression of collagen II protein; and upregulation of collagen II, aggrecan, and SOX9 genes. Therefore, our work presents a robust method for chondrogenesis of MSCs using magnetic field as the external cue.