Objective: To investigate the mobilization of peripheral blood mesenchymal stem cells (PBMSCs) and whether a combination of PBMSCs and modified demineralized bone matrix (DBM) promoted the repair of cartilage lesions in a pig model. Methods: Pig PBMSCs were mobilized by the combined administration of granulocyte colony-stimulating factor (G-CSF) and the CXCR4 antagonist AMD3100. Colony formation was detected by the fibroblast colony-forming unit (CFU-F) count and the percentage of the CD45–CD90+ cell population by flow cytometry. The mobilized cells were identified as MSCs by their morphological characteristics, surface markers, and differentiation potentials. The composite scaffolds carrying BMP-2 and TGF-β₃ chitosan sustained-release microspheres/DBM were prepared by emulsion cross-linking and the Urist method, and scanning electron microscopy (SEM) observation was performed. The model of pig cartilage defect was prepared, and gross observation, histological examination, immunohistochemistry, and O’Driscoll scoring were performed 4, 8, and 12 weeks postoperation. Results: After mobilization, the number of CFU-Fs in the peripheral blood in the experimental group (G-CSF + AMD3100) was significantly increased compared with the control group (p < 0.05). The proportion and total number of CD45–CD90+ cells were increased (p < 0.05). The mobilized stem cells had MSC characteristics. SEM of the new tissue-engineered cartilage showed that PBMSCs were evenly grown on the surface of the scaffold and microsphere morphology had no obvious change. Gross observation, histological examination, immunohistochemistry, and O’Driscoll score were better in the experimental group than in the other groups (p < 0.05). Conclusion: G-CSF + AMD3100 is an effective mobilization agent for PBMSCs. The new tissue-engineering cartilage constructed by two-factor sustained-release microspheres/DBM composite PBMSCs effected good repair of the cartilage defect in pigs.

Background: Multiple knee ligament injuries combined with extensor apparatus rupture are serious and complex knee injuries that are rare in clinical practice. The management is extremely challenging and controversial. The aim of this study is to describe a patient collective with multiple knee ligament injuries combined with extensor apparatus injuries in detail and to report the mid-term outcomes of a one-stage surgical treatment regarding subjective outcome scores, complications, knee instability, and ROM. Methods: Eleven of 425 patients with multiple knee ligament injuries combined with extensor apparatus injuries admitted to our hospital were reviewed from July 2008 to May 2017. All patients underwent one-stage repair and reconstruction of multiple knee ligaments and extensor apparatus. The Lysholm knee score and the International Knee Documentation Committee (IKDC) score were adopted to evaluate the surgical effect preoperatively and at a minimum of 2 years' follow-up. Clinical data, including range of motion and knee stability, were also recorded at the final follow-up. Results: Ten patients were followed up with a mean time of 40 (range, 24-60) months. At the last follow-up, 8 patients had joint flexion range of motion greater than or equal to120 degrees, 2 patients had joint flexion range of motion of 100-120 degrees, and 1 patient had active knee extension limitation of 5 degrees. Stress radiographs showed that the mean differences in posterior displacement were reduced from 10.8 ± 3.0 mm preoperatively to 2.0 ± 2.5 mm at the last follow-up. There were significant improvements in stress radiographs from pre-to postoperative states for all patients with multiple knee ligament injuries. The Lysholm score ranged from 85 to 96, with a mean of 92.1 (compared with 33 before surgery, P < 0.05). The final IKDC scores were A in 2 patients (20%), B in 7 (70%), and C in 1 (10%). Nine of the 10 patients (90%) returned to their former activity level. Conclusion: Multiple knee ligament injuries combined with extensor apparatus rupture are rare. Single-stage management of the repair and reconstruction of multiple knee ligaments and extensor apparatus with proper rehabilitation is an effective and reliable procedure to restore knee stability and function. Level of evidence: Level IV, therapeutic case series.

AbstractcircRNAs play an important role in the progression of osteoarthritis (OA). Therefore, we aimed to reveal the mechanism of action of circRNA-ZCCHC14 in OA. OA animal and cell models were constructed, and clinical samples were collected. The expression of circRNA-ZCCHC14 and miR-181a was detected by RT‒qPCR. The chondrogenic differentiation ability of peripheral blood-derived mesenchymal stem cells (PBMSCs) was detected by Alcian blue staining. The expression of chondrogenic differentiation-related proteins was detected by Western blotting. Double fluorescein experiments verified the targeting relationship of miR-181a with circRNA-ZCCHC14 and GREM1. Upregulation of circRNA-ZCCHC14 was observed in blood, in BMP-2- and TGF-β3-treated PBMSCs from OA patients and in animal models. Knockdown of circRNA-ZCCHC14 promoted the chondrogenic differentiation ability of PBMSCs. circRNA-ZCCHC14 was found to bind to miR-181a and negatively regulate miR-181a expression. Inhibition of miR-181a reversed the promoting effect of circRNA-ZCCHC14 knockdown on the chondrogenic differentiation ability of PBMSCs. GREM1 was identified as a target of miR-181a. Overexpression and knockdown of GREM1 regulated the expression of BMP2, which in turn affected the chondrogenic differentiation ability of PBMSCs, indicating that GREM1 and BMP2 have antagonistic effects and that they jointly regulate the chondrogenic differentiation of PBMSCs. circRNA-ZCCHC14 may promote the chondrogenic differentiation ability of PBMSCs by regulating miR-181a and inhibiting the expression of GREM1.