Background: Total meniscectomy leads to knee osteoarthritis in the long term. The poly(ε-caprolactone) (PCL) scaffold is a promising material for meniscal tissue regeneration, but cell-free scaffolds result in relatively poor tissue regeneration and lead to joint degeneration. Hypothesis: A novel, 3-dimensional (3D)–printed PCL scaffold augmented with mesenchymal stem cells (MSCs) would offer benefits in meniscal regeneration and cartilage protection. Study Design: Controlled laboratory study. Methods: PCL meniscal scaffolds were 3D printed and seeded with bone marrow–derived MSCs. Seventy-two New Zealand White rabbits were included and were divided into 4 groups: cell-seeded scaffold, cell-free scaffold, sham operation, and total meniscectomy alone. The regeneration of the implanted tissue and the degeneration of articular cartilage were assessed by gross and microscopic (histological and scanning electron microscope) analysis at 12 and 24 weeks postoperatively. The mechanical properties of implants were also evaluated (tensile and compressive testing). Results: Compared with the cell-free group, the cell-seeded scaffold showed notably better gross appearance, with a shiny white color and a smooth surface. Fibrochondrocytes with extracellular collagen type I, II, and III and proteoglycans were found in both seeded and cell-free scaffold implants at 12 and 24 weeks, while the results were significantly better for the cell-seeded group at week 24. Furthermore, the cell-seeded group presented notably lower cartilage degeneration in both femur and tibia compared with the cell-free or meniscectomy group. Both the tensile and compressive properties of the implants in the cell-seeded group were significantly increased compared with those of the cell-free group. Conclusion: Seeding MSCs in the PCL scaffold increased its fibrocartilaginous tissue regeneration and mechanical strength, providing a functional replacement to protect articular cartilage from damage after total meniscectomy. Clinical Relevance: The study suggests the potential of the novel 3D PCL scaffold augmented with MSCs as an alternative meniscal substitution, although this approach requires further improvement before being used in clinical practice.

Anisotropic meniscus engineered using biomechanical, biochemical, and structural cues demonstrates long-term knee chondroprotection in rabbits.

Osteoarthritis (OA) is a progressive joint disease characterized by inflammation and cartilage destruction, and its progression is closely related to imbalances in the M1/M2 synovial macrophages. A two‐pronged strategy for the regulation of intracellular/extracellular nitric oxide (NO) and hydrogen protons for reprogramming M1/M2 synovial macrophages is proposed. The combination of carbonic anhydrase IX (CA9) siRNA and NO scavenger in “two‐in‐one” nanocarriers (NAHA‐CaP/siRNA nanoparticles) is developed for progressive OA therapy by scavenging NO and inhibiting CA9 expression in synovial macrophages. In vitro experiments demonstrate that these NPs can significantly scavenge intracellular NO similar to the levels as those in the normal group and downregulate the expression levels of CA9 mRNA (≈90%), thereby repolarizing the M1 macrophages into the M2 phenotype and increasing the expression levels of pro‐chondrogenic TGF‐β1 mRNA (≈1.3‐fold), and inhibiting chondrocyte apoptosis. Furthermore, in vivo experiments show that the NPs have great anti‐inflammation, cartilage protection and repair effects, thereby effectively alleviating OA progression in both monoiodoacetic acid‐induced early and late OA mouse models and a surgical destabilization of medial meniscus‐induced OA rat model. Therefore, the siCA9 and NO scavenger “two‐in‐one” delivery system is a potential and efficient strategy for progressive OA treatment.

The regeneration of osteochondral tissue necessitates the re-establishment of a gradient owing to the unique characteristics and healing potential of the chondral and osseous phases. As the self-healing capacity of hyaline cartilage is limited, timely mechanical support during neo-cartilage formation is crucial to achieving optimal repair efficacy. In this study, we devised a biodegradable bilayered scaffold, comprising chondroitin sulfate (CS) hydrogel to regenerate chondral tissue and a porous pure zinc (Zn) scaffold for regeneration of the underlying bone as mechanical support for the cartilage layer. The photocured CS hydrogel possessed a compressive strength of 82 kPa, while the porous pure Zn scaffold exhibited a yield strength of 11 MPa and a stiffness of 0.8 GPa. Such mechanical properties are similar to values reported for cancellous bone. In vitro biological experiments demonstrated that the bilayered scaffold displayed favorable cytocompatibility and promoted chondrogenic and osteogenic differentiation of bone marrow stem cells. Upon implantation, the scaffold facilitated the simultaneous regeneration of bone and cartilage tissue in a porcine model, resulting in (i) a smoother cartilage surface, (ii) more hyaline-like cartilage, and (iii) a superior integration into the adjacent host tissue. Our bilayered scaffold exhibits significant potential for clinical application in osteochondral regeneration.

Osteochondral lesions (OCLs) and bony impingement are common secondary lesions of chronic lateral ankle instability (CLAI), but the risk factors that predict OCLs and bony impingement are unknown. To analyze the risk factors for the development of OCLs and osteophytes in patients with CLAI. Case-control study; Level of evidence, 3. Patients diagnosed with CLAI at our institution from June 2007 to May 2018 were enrolled. The assessed potential risk factors were age, sex, postinjury duration, body mass index, injury side, and ligament injury type (isolated anterior talofibular ligament [ATFL] injury, isolated calcaneofibular ligament [CFL] injury, or concomitant ATFL and CFL injuries). Univariate and multivariate logistic regression analyses were performed to evaluate the association between these factors and the presence of OCLs and osteophytes. A total of 1169 patients with CLAI were included; 436 patients (37%) had OCLs and 334 (31%) had osteophytes. The presence of OCLs was significantly associated with the presence of osteophytes (P < .001). Male sex and older age were significantly associated with the presence of OCLs in the medial and lateral talus. A postinjury duration of 5 years or longer was significantly associated with the presence of OCLs in the medial talus (odds ratio [OR], 1.532; 95% CI, 1.023-2.293; P = .038) but not in the lateral talus. ATFL and CFL injuries were both significantly associated with the presence of lateral OCLs. Risk factors for the presence of osteophytes were male sex, older age, postinjury duration 5 years or longer, and CFL injury. Patients with concomitant ATFL and CFL injuries were significantly more likely to have osteophytes than were patients with single-ligament injuries (P = .018). Risk factors for OCLs and osteophytes were postinjury duration of 5 years or longer, older age, and male sex. ATFL injury was associated with the presence of lateral OCLs, whereas CFL injury was associated with the presence of lateral OCLs and osteophytes. Patients with these risk factors should be closely monitored and treated to reduce the incidence of ankle arthritis.