Organoids, self-organized structures derived from stem cells cultured in a specific three-dimensional (3D) in vitro microenvironment, have emerged as innovative platforms that closely mimic in vivo cellular behavior, tissue architecture, and organ function. Bone organoids, a frontier in organoid research, can replicate the complex structures and functional characteristics of bone tissue. Recent advancements have led to the successful development of bone organoids, including models of callus, woven bone, cartilage, trabecular bone, and bone marrow. These organoids are widely utilized in establishing bone-related disease models, bone injury repair, and drug screening. However, significant discrepancies remain between current bone organoids and human skeletal tissues in terms of morphology and functionality, limiting their ability to accurately model human bone physiology and pathology. To address these challenges and promote standardization in the construction, evaluation, and application of bone organoids, we have convened experts and research teams with substantial expertise in the field. By integrating existing research findings, this consortium aims to establish a consensus to guide future research and application of bone organoids.

The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton’s jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-β/Smad2/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50 µg/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-β, and Smad2/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery. Graphical abstract

Alcohol-induced osteonecrosis of the femoral head (ONFH) is a disabling disease with a high incidence and elusive pathogenesis. Here, we used single-cell RNA sequencing to explore the transcriptomic landscape of mid- and advanced-stage alcohol-induced ONFH. Cells derived from age-matched hip osteoarthritis and femoral neck fracture samples were used as control. Our bioinformatics analysis revealed the disorder of osteogenic-adipogenic differentiation of stromal cells in ONFH and altered regulons such as MEF2C and JUND. In addition, we reported that one of the endothelial cell clusters withACKR1expression exhibited strong chemotaxis and a weak angiogenic ability and expanded with disease progression. Furthermore, ligand-receptor-based cell-cell interaction analysis indicated that ACKR1+ endothelial cells might specifically communicate with stromal cells through the VISFATIN and SELE pathways, thus influencing stromal cell differentiation in ONFH. Overall, our data revealed single cell transcriptome characteristics in alcohol-induced ONFH, which may contribute to the further investigation of ONFH pathogenesis.

Achieving self‐healing for osteochondral defects caused by trauma, aging, or disease remains a significant challenge in clinical practice. It is an effective therapeutic strategy to construct gradient‐biomimetic biomaterials that replicate the hierarchical structure and complex microenvironment of osteochondral tissues for dual‐lineage regeneration of both cartilage and subchondral bone. Herein, ROS‐activated nanohydrogels composite bilayer scaffolds with multi‐factors controlled release are rationally designed using the combination of 3D printing and gelatin placeholder methods. The resulting nanohydrogel scaffolds exhibit micro‐nano interconnected porous bilayer structure and soft‐hard complex mechanical strength for facilitating 3D culture of BMSCs in vitro. More importantly, multi‐stage continuous responses of anti‐inflammation, chondrogenesis and osteogenesis, are effectively induced via the sequential release of multi‐factors, including diclofenac sodium (DS), kartogenin (KGN) and bone morphogenetic protein 2 (BMP‐2), from ROS‐activated nanohydrogel scaffolds, thereby improved dual‐lineage regeneration of cartilage and subchondral bone tissue in the osteochondral defect model of SD rats. These findings suggest that ROS‐activated nanohydrogel scaffolds with such specific soft‐hard bilayer structure and sequential delivery of functional factors, provides a promising strategy in dual‐lineage regeneration of osteochondral defects.

Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of articular cartilage and secondary osteogenesis. Cell-based agents, such as mesenchymal stem cells, have turned into the most extensively explored new therapeutic agents for OA. However, evidence-based research is still lacking. We searched public databases up to February 2020 and only included randomized controlled trials. The outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Knee Injury and Osteoarthritis Outcome Score (KOOS), the visual analogue scale (VAS) score, and serious adverse events (SAEs). A network meta-analysis was also performed in this work. We included 13 studies in the meta-analysis. The effect size showed that cell-based therapy did not significantly reduce the WOMAC score at the 6-month follow-up (standard mean difference [SMD] −3.6; 95% confidence interval [CI] −0.90 to 0.18; P = 0.1928). However, cell-based therapy significantly improved the KOOS at the 12-month follow-up (SMD 0.68; 95% CI 0.07-1.30; P = 0.0288) and relieved pain (SMD −1.05; 95% CI −1.46 to −0.64; P < 0.0001). The findings also indicated that high-dosage adipose-derived mesenchymal stem cells (ADMSCs) may be more advantageous in terms of long-term effects. Cell-based therapy had a better effect on KOOS improvement and pain relief without safety concerns. However, cell-based therapy did not show a benefit in terms of the WOMAC. Allogeneic cells might have advantages compared to controls in the WOMAC and KOOS scores. The long-term effect of high-dose ADMSC treatment for OA is worthy of further study.

Background: Avulsion fracture of the tibial intercondylar eminence is a rare injury, which mainly occurs in adolescents aged 8–14 years and in those with immature bones. The current commonly used surgery may result in severe surgical trauma, affecting knee joint function and accompanied by serious complications. In this study, we described an all-inside and all-epiphyseal arthroscopic suture fixation technique for a patient to treat tibial intercondylar eminence fracture. Methods: ETHIBOND EXCEL-coated braided polyester sutures were used for fixation. Three ETHIBOND sutures were passed through the ACL at 2, 6 and 10 o’clock of the footprint of the ACL and made a cinch-knot loop separately. Under the guidance of ACL tibial locator, three corresponding tibial tunnels were drilled with K-wires at 2, 6 and 10 o’clock of the fracture bed, and the two ends of the suture were pulled out through the tunnel with double-folded steel wire heads. After reduction of the tibial eminence, three sutures were tightened and tied to the medial aspect of the tibial tubercle. Results: After all the surgical treatments surgically performed by this method and following a standard postoperative protocol, our patient's ROM, stability, and functional structural scores all improved significantly. Conclusion: This three-point suture technique provides a suitable reduction and stable fixation and is suitable for patients with all types of avulsion fractures of the tibial intercondylar eminence.