Development of a novel approach for restoration of the meniscus using silk-elastin in a rabbit meniscus injury model.

BACKGROUND: Limited healing potential of the meniscus remains a burden for the successful repair of meniscus injuries in the orthopaedic fields. Silk-elastin (SE) is a novel recombinant protein with favorable properties for wound healing. This proof-of-concept study aimed to investigate the therapeutic effect of silk-elastin in a rabbit meniscal defect model. METHODS: A migration assay using rabbit meniscus and synovial cells with various concentrations of SE in a culture medium was conducted to investigate the mechanism of meniscal healing by SE. Additionally, cylindrical defects with a 1.5 mm diameter were created at the anterior horn of the medial meniscus of rabbits. The animals were divided into three groups: 1) the Blank group; defect only, 2) the Col I group; implantation of type I atelocollagen sponge, and 3) the SE group; implantation of SE (150 mg/ml) sponge. Whole medial menisci were harvested at 4, 8, 12, and 24 weeks after surgery. Histological analyses including immunohistochemical staining were performed to assess meniscal healing. RESULTS: In vitro study, Migration assay demonstrated a significantly higher number of migrated cells only in synovial cells. Especially, the SE concentration of 10 µg/mL demonstrated the highest number of migrated cells compared with other concentrations. In vivo study, the SE group exhibited significantly higher Ishida scores than other groups at all time points. Furthermore, the SE group showed higher synovial coverage scores than the Col I group at 4 and 8 weeks. Immunohistochemical staining demonstrated higher type II collagen staining in the SE group compared to other groups at 12 weeks. Implanted SE was efficiently replaced by safranin-O staining positive tissue within 8 weeks. CONCLUSIONS: SE could effectively repair a meniscal defect by inducing coverage of synovial cells. SE has the potential to be a useful material for meniscal repair.

The posterior condyle grows in the direction of the increasing posterior condylar offset and the inclination angle of the ACL changes accordingly.

PURPOSE: The purpose of this study was to reveal the changes in the shape of the posterior femoral condyle and the morphology of the ACL, both before and after epiphyseal closure. The hypothesis of this study is that the morphological change of the posterior femoral condyle and that of the ACL may be correlated to some extent. METHODS: Eighty-one patients who underwent surgery for the knee joint (meniscal repair, arthroscopic synovectomy, medial patellofemoral ligament reconstruction) between 2016 and 2021 were included in this study, 48 patients aged 13 years or under (before epiphysis closure; mean age: 10.9 (range: 7-13) and 33 patients aged over 18 years or over (after epiphysis closure; mean age: 21.7 (range: 18-30). The shape of the posterior femoral condyle was evaluated via lateral view radiographs, and the morphology of the ACL was measured via sagittal and coronal magnetic resonance imaging (MRI) images. RESULTS: The morphology of the posterior condyle in the lateral view radiograph in patients aged 13 and under was larger in the direction of the short axis of the femur compared with that in those aged 18 and over (p < 0.001). The mean value of the inclination angle of the anterior cruciate ligament (ACL) in the sagittal plane was significantly smaller in patients aged 13 and under (41.7° ± 3.7) than in those aged 18 and over (48.5° ± 4.2) (p < 0.001). The mean values of the inclination angle of the ACL in the coronal plane were significantly smaller in patients aged 13 and under (55.7° ± 6.4) than in those aged 18 and over (63.4° ± 4.4) (p < 0.001). CONCLUSION: This study evaluates and compares the shape of the posterior femoral condyle and the morphology of the ACL fiber before and after epiphyseal closure. The posterior femoral condyle grew posteriorly rather than longitudinally, and the inclination of the ACL fibers was thought to change accordingly. LEVEL OF EVIDENCE: Level Ⅲ.

Human Trials on the Prevention of Tunnel Widening by the Emdogain in Anterior Cruciate Ligament Reconstruction.

Background Although anterior cruciate ligament reconstruction (ACLR) is an established procedure, some problems remain, such as bone tunnel widening after ACLR. In animal studies, Emdogain (EMD) prevented tunnel widening by promoting tendon-bone healing. This study aimed to evaluate the effects of EMD on the prevention of tunnel widening after anterior cruciate ligament (ACL) injury in humans. Methods Nineteen patients who underwent ACLR were included. Seven patients in the EMD group were administered EMDs into the femoral tunnel during ACLR, while 12 patients in the control group were not administered EMDs. After surgery, at two and four weeks and three, six, and 12 months, femoral and tibial tunnel widening were evaluated on computed tomography images. Anteroposterior laxity and clinical scores such as the Lysholm score, the International Knee Documentation Committee (IKDC) subjective form, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were assessed before surgery and 12 months postoperatively. Results Tunnel widening on the femoral side was significantly smaller in the EMD group than in the control group at two weeks. However, there was no significant difference between the two groups at 12 months. There were no significant differences in anteroposterior laxity and clinical scores between the groups before and 12 months after surgery. Conclusion EMD administration into the bone tunnel did not prevent tunnel widening at 12 months after ACLR, although tunnel widening of the femoral tunnel was reduced by EMD administration in the early phase.

Changes in the Subchondral Bone Affect Pain in the Natural Course of Traumatic Articular Cartilage Defects.

OBJECTIVE: Articular cartilage defect causes joint pain and finally progresses to osteoarthritis. Although the subchondral bone condition affects clinical outcomes of cartilage defects, the natural course of changes in subchondral bone and associated pain in full-thickness cartilage defects remain unknown. Therefore, we investigated the natural course of histological changes in subchondral bone and joint pain in cartilage defects using a rat model. DESIGN: Full-thickness cartilage defects were created at the medial femoral condyle of 10-week-old male Sprague-Dawley rats. Rats were sacrificed at 3, 7, 14, 28, and 56 days postoperatively, and histological including immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining and micro-computed tomography (µCT) analyses of their knees were performed. Pain was evaluated using behavioral analysis and immunofluorescence staining of the dorsal root ganglion (DRG). RESULTS: The contour of the subchondral bone plate was maintained until day 3, but it was absorbed just under the cartilage defect from day 7 to 14. Starting on day 28, sclerotic changes surrounding the bone absorption area were detected. In the subchondral bone, the number of TRAP-positive cells peaked on day 14. Osteocalcin-positive cells were observed at 7 days, and their number gradually increased till day 56. Behavioral analysis showed that the total distance and the number of getting up by hind legs decreased on day 14. The number of calcitonin gene-related peptide-positive fibers in the DRG increased and was the highest on day 14. CONCLUSIONS: The subchondral bone condition under cartilage defects dynamically changes from bone resorption to sclerosis and is related to pain level.

Comparison of clinical outcomes between anterior cruciate ligament reconstruction with over-the-top route procedure and anatomic single-bundle reconstruction in pediatric patients.

The purpose of this study is to evaluate the clinical results of over-the-top route (OTTR) reconstruction for pediatric anterior cruciate ligament (ACL) injuries and compare them with results of anatomic single-bundle reconstruction (SBR), which used the bone tunnel technique and was performed early after epiphyseal closure (age ≤15 years). This study included pediatric patients aged 11-15 years who underwent ACL reconstruction. The mean age at surgery was 13.4 years (11-15 years), including 14 men and 29 women. Operative procedures were determined according to growth plate closure. In all cases, the tibial side was reconstructed using a bone tunnel procedure. On the femoral side, we selected the OTTR procedure (group O) with open physis. Where the physis was closed, we selected the anatomical SBR (group B). The clinical results were evaluated with manual examination, the side-to-side difference (SSD) in tibial anterior translation using the Kneelax 3, and knee function score. There were no significant differences in the Lachman and pivot-shift tests, SSD in tibial anterior translation with Kneelax 3, or knee function score between the two groups before or after the surgery. Growth disturbance was not observed on either the femoral or tibial side in group O. The OTTR method provided comparable results with the bone tunnel anatomical method in manual examination, Kneelax 3, and knee clinical function scores, suggesting that the OTTR method is very useful for pediatric ACL reconstructions. Level of evidence: III; retrospective study.

Posterior wall blowout on computed tomography after anterior cruciate ligament reconstruction.

BACKGROUND: During anterior cruciate ligament (ACL) reconstruction, even when a posterior wall of the femoral bone tunnel is identified, computed tomography (CT) occasionally demonstrates a breach of the posterior femoral cortex of the femoral bone tunnel, i.e., posterior wall blowout, after ACL reconstruction (posterior wall blowout-like phenomenon). This study aimed to investigate the influence of the posterior wall blowout-like phenomenon on clinical outcomes after ACL reconstruction using hamstring tendon. METHODS: A total of 105 patients who underwent CT examination two weeks after ACL reconstruction were enrolled. A cortical suspension device was used for femoral side fixation in all cases. Posterior wall was identified in all cases during the surgery. The side-to-side difference in anterior knee laxity, pivot shift test, Lysholm knee score, the International Knee Documentation Committee (IKDC) subjective form, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were evaluated one year after the surgery. A second CT examination was performed 6-12 months after the surgery, if a posterior wall blowout-like phenomenon was identified in the first CT examination. RESULTS: Two weeks after the surgery, 16 of the 105 patients showed a posterior wall blowout-like phenomenon. Twelve of the 16 cases demonstrated a regenerated posterior femoral cortex of the femoral bone tunnel on their second CT images. There were no significant differences between the posterior wall blowout-like phenomenon group and the normal posterior wall group in terms of a side-to-side difference in anterior knee laxity (0.4 ± 1.5 mm and 0.1 ± 1.6 mm, respectively), pivot shift test, Lysholm knee score, IKDC score, and KOOS at one year after surgery. The length and diameter of the femoral bone tunnel were not significantly different between the two groups. CONCLUSIONS: Posterior wall blowout-like phenomenon after ACL reconstruction using a cortical suspension device did not negatively influence clinical outcomes. LEVEL OF EVIDENCE: III - retrospective comparative clinical study.

Equivalent outcomes of ACL revision with over-the-top single and double-bundle reconstruction using hamstring tendon compared to anatomical single and double-bundle reconstruction.

PURPOSE: In revision anterior cruciate ligament reconstruction (ACLR), our procedure of choice is the over-the-top route (OTTR) for cases where it is difficult to use a primary bone tunnel or to create a new bone tunnel due to the enlargement or malposition of the bone tunnel. Depending on the condition of the primary bone tunnel, we choose single (bone tunnel or OTTR) or double (bone tunnel or anteromedial (AM) bundle: OTTR /posterolateral (PL) bundle: bone tunnel) for femoral fixation. This study showed the results of single and double OTTR revision ACLR using the hamstring tendon. METHODS: Seventy-eight patients, who underwent revision ACLR using the hamstring tendon and who could be followed up for more than 2 year, were included in this study. The methods of revision ACLR were single in 54 cases (bone tunnel: 24 cases; OTTR method: 30 cases) and double in 24 cases (bone tunnel: 16 cases; OTTR for AM bundle and bone tunnel for PL bundle: eight cases). The cause of re-injury, the meniscus and cartilage injury, the reconstruction method, and the Lysholm score, Lachman test, Pivot-shift test, and the side-to-side difference in the tibial anterior translation were evaluated before and after surgery. RESULTS: There was no statistically significant difference in the Lyshom score, Lachman / Pivotshift test and side-to-side difference anterior translation of the tibia between the four groups. CONCLUSIONS: The clinical results of single and double OTTR revision ACLR are equivalent to those of anatomic single and double bone tunnel procedures.

The therapeutic capacity of bone marrow MSC-derived extracellular vesicles in Achilles tendon healing is passage-dependent and indicated by specific glycans.

The therapeutic potential of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) for various diseases and tissue repair is attracting attention. Here, EVs from conditioned medium of human bone marrow MSCs at passage 5 (P5) and passage 12 (P12) were analysed using mouse Achilles tendon rupture model and lectin microarray. P5 MSC-EVs accelerated Achilles tendon healing compared with P12 MSC-EVs. Fucose-specific lectin TJA-II was indicated as a glycan marker for therapeutic MSC-EVs. The present study demonstrated that early passaged MSC-EVs promote Achilles tendon healing compared with senescent MSC-EVs. Glycans on MSC-EVs might provide useful tools to establish a quality control and isolation system for therapeutic MSC-EVs in regenerative medicine.

Evaluation of the flexion gap with a distal femoral trial component in posterior-stabilized total knee arthroplasty.

PURPOSE: A distal femoral trial component was manufactured, and flexion gap size and inclination were evaluated with or without the distal femoral trial component in total knee arthroplasty (TKA). This study aimed to evaluate the effect of the distal femoral trial component on flexion gap size and joint inclination in posterior-stabilized (PS)-TKA. MATERIALS AND METHODS: A total of 84 patients with medial osteoarthritis who underwent mobile-bearing PS-TKA using modified gap techniques were included in this retrospective study. The flexion gap size and inclination before and after setting the distal femoral trial component were evaluated and compared with the final gap size and inclination. RESULTS: The joint gap size and inclination were significantly lower in those with than in those without the distal femoral trial component (P = 0.005, P < 0.001). The final gap size and inclination were similar to the gap size and inclination with the distal trial component (P = 0.468, P = 0.158). CONCLUSIONS: The joint gap size and medial tension in PS-TKA were significantly reduced after setting the distal femoral trial component. The flexion gap measured using the distal femoral trial component was similar to that when the final trial component was set. To more accurately perform the gap technique TKA, the flexion gap should be measured using the distal femoral trial component.

PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes.

PD-1 blockade exerts clinical efficacy against various types of cancer by reinvigorating T cells that directly attack tumor cells (tumor-specific T cells) in the tumor microenvironment (TME), and tumor-infiltrating lymphocytes (TILs) also comprise nonspecific bystander T cells. Here, using single-cell sequencing, we show that TILs include skewed T cell clonotypes, which are characterized by exhaustion (Tex) or nonexhaustion signatures (Tnon-ex). Among skewed clonotypes, those in the Tex, but not those in the Tnon-ex, cluster respond to autologous tumor cell lines. After PD-1 blockade, non-preexisting tumor-specific clonotypes in the Tex cluster appear in the TME. Tumor-draining lymph nodes (TDLNs) without metastasis harbor a considerable number of such clonotypes, whereas these clonotypes are rarely detected in peripheral blood. We propose that tumor-infiltrating skewed T cell clonotypes with an exhausted phenotype directly attack tumor cells and that PD-1 blockade can promote infiltration of such Tex clonotypes, mainly from TDLNs.

A Comparison of Central Anatomic Single-Bundle Reconstruction and Anatomic Double-Bundle Reconstruction in Anteroposterior and Rotational Knee Stability: Intraoperative Biomechanical Evaluation.

Postoperative anterior and rotational stability are still controversial when compared with single-bundle (SB) and double-bundle (DB) anterior cruciate ligament (ACL) reconstruction. This study aimed to compare the central anatomical SB and anatomical DB ACL reconstruction in intraoperative knee kinematics during continuous knee flexion-extension. A total of 34 patients who underwent ACL reconstruction using the hamstring tendon were evaluated intraoperatively before and immediately after ACL reconstruction using OrthoPilot ACL Navigation System Version 3.0. The patients were prospectively randomized into the central anatomical SB (17 knees) and the anatomical DB reconstruction (17 knees) groups. The tibial translation and rotation were continuously measured during knee flexion-extension under conventional knee motion, anterior tibial load (100N), and internal-external torque (3 N·m). The anterior tibial translation and total range of tibial rotation were calculated from the measurement values from 20 to 50 degrees at each 5-degree point. The anterior tibial translation (p = 0.59; two-factor repeated measures analysis of variance; η 2G = 0.0077) and total range of tibial rotation (p = 0.95; η 2G = 0.0001) at each knee flexion angle showed no significant difference between the central anatomical SB and anatomical DB reconstruction groups. It is suggested that the central anatomical SB reconstruction is comparable with the anatomical DB reconstruction in biomechanical anteroposterior and rotational knee stability at time 0.

An older age, a longer duration between injury and surgery, and positive pivot shift test results increase the prevalence of articular cartilage injury during ACL reconstruction in all three compartments of the knee in patients with ACL injuries.

PURPOSE: To investigate factors that influence the prevalence of articular cartilage injury in patients with anterior cruciate ligament (ACL) injury. METHODS: This multicentre study included patients with ACL injury. Logistic regression analysis was conducted to identify factors that influence the prevalence of cartilage injury during ACL reconstruction. RESULTS: A total of 811 patients were enrolled. The factors that significantly influenced the prevalence of cartilage injury were age (odds ratio [OR], 1.04; P = 0.000), a positive pivot shift test result (OR, 1.43; P = 0.021), medial meniscal injury (OR, 2.55; P = 0.000), and delayed surgery (≥ 12 months) (OR, 2.52; P = 0.028) in the medial compartment of the knee; age (OR, 1.05; P = 0.000), subjective grades of apprehension during the pivot shift test (OR, 1.46; P = 0.010), lateral meniscal injury (OR, 1.98; P = 0.003), femoro-tibial angle (FTA) (OR, 0.92; P = 0.006), and delayed surgery (≥ 12 months) (OR, 2.63; P = 0.001) in the lateral compartment; and age (OR, 1.06; P = 0.000), body mass index (OR, 1.07; P = 0.028), a positive pivot shift test result (OR, 1.60; P = 0.018), FTA (OR, 0.90; P = 0.006), and delayed surgery (≥ 12 months) (OR, 3.17; P = 0.008) in the patellofemoral compartment. CONCLUSION: An older age, a longer duration between injury and surgery, and a positive pivot shift test result were positively associated with the prevalence of cartilage injury in three compartments in patients with ACL injuries. Early ACL reconstruction is recommended to prevent cartilage injury. LEVEL OF EVIDENCE: Level III.

A larger side-to-side difference in anterior knee laxity increases the prevalence of medial and lateral meniscal injuries in patients with ACL injuries.

PURPOSE: The objective of this study was to investigate factors that influence the prevalence of medial and lateral meniscal injuries at the time of anterior cruciate ligament (ACL) reconstruction in patients with ACL injuries. METHODS: Patients with ACL injuries at 9 institutions were enrolled in this multicentre study. Age, sex, duration between injury and surgery, pivot shift test grade, anterior knee laxity determined using the Kneelax 3 arthrometer, and other variables were assessed by logistic regression analysis. Meniscal conditions were evaluated via arthroscopy. RESULTS: In all, 830 patients were enrolled. The prevalence of medial and lateral meniscal tears was 32.0% (266 knees) and 26.5% (220 knees), respectively. Significant factors that influenced the prevalence of medial meniscal injuries were age [odds ratio (OR) 1.03; P = 0.000], side-to-side differences in instrumented anterior knee laxity before surgery (OR 1.12; P = 0.002), duration between injury and surgery (≥ 12 months) (OR 1.86; P = 0.023), and pivot shift test grade (OR 1.36; P = 0.014). Significant factors of lateral meniscal injury were side-to-side differences in anterior knee laxity before surgery (OR 1.12; P = 0.003) and the male sex (OR 1.50; P = 0.027). CONCLUSION: Greater anterior knee laxity, age, a longer duration between injury and surgery, and a higher pivot shift test grade predicted medial meniscal injury. Greater anterior knee laxity and the male sex predicted lateral meniscal injury. In patients with ACL injuries, the importance of side-to-side differences in anterior knee laxity should be rediscovered from the viewpoint of meniscal conditions. LEVEL OF EVIDENCE: Level III.

Clinical outcomes of knee joint distraction combined with marrow stimulation procedures for patients with advanced knee osteoarthritis.

BACKGROUND: Knee joint distraction (KJD) has received much attention as a joint preserving surgery, especially in young patients with advanced knee osteoarthritis (OA). METHODS: This study included 16 patients with advanced knee OA who underwent KJD combined with marrow stimulating techniques and were followed up for more than 2 years. The patients' clinical scores, including the Japanese Orthopaedic Association (JOA) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, ROM, joint space width, and semiquantitative MRI were evaluated. The factors affecting clinical outcomes were analyzed. RESULTS: Postoperatively, the JOA score and the individual scores of the KOOS subscales improved significantly (JOA score: P = 0.0028, KOOS-symptoms: P = 0.0016, -pain: P = 0.0011, -ADL: P = 0.0009, -sports/recreation: P = 0.0144, and -QOL: P = 0.0034). Although the extension of the knee joint did not change throughout the follow-up period, flexion of the joint deteriorated at the time of device removal but recovered to the preoperative level at the final follow-up. Preoperative joint space width was 2.4 ± 2.0 mm and at the final follow-up, it increased to 3.3 ± 1.5 mm, showing statistically significant improvement (P = 0.034). The postoperative semiquantitative MRI score also improved significantly (from 6.0 ± 3.0 to 42.1 ± 28.7, P = 0.0001). A high BMI was associated with a poor clinical outcome. CONCLUSION: Although the effect of marrow stimulating techniques for cartilage repair was not well clarified and the complication rate was high, the clinical and radiographic outcomes showed significant improvement after KJD combined with marrow stimulating techniques in patients with advanced knee OA. However, we should be careful about suggesting this procedure in obese patients.

Carbon-nanotube yarns induce axonal regeneration in peripheral nerve defect.

Carbon nanotubes (CNTs) are cylindrical nanostructures and have unique properties, including flexibility, electrical conductivity, and biocompatibility. We focused on CNTs fabricated with the carbon nanotube yarns (cYarn) as a possible substrate promoting peripheral nerve regeneration with these properties. We bridged a 15 mm rat sciatic nerve defect with five different densities of cYarn. Eight weeks after the surgery, the regenerated axons crossing the CNTs, electromyographical findings, and muscle weight ratio of the lower leg showed recovery of the nerve function by interfacing with cYarn. Furthermore, the sciatic nerve functional index (SFI) at 16 weeks showed improvement in gait function. A 2% CNT density tended to be the most effective for nerve regeneration as measured by both histological axonal regeneration and motor function. We confirmed that CNT yarn promotes peripheral nerve regeneration by using it as a scaffold for repairing nerve defects. Our results support the future clinical application of CNTs for bridging nerve defects as an off-the-shelf material.

Application of a true lateral virtual radiograph from 3D-CT to identify the femoral reference point of the medial patellofemoral ligament.

PURPOSE: The purpose of this study is two-fold: (1) to describe the femoral reference point of the medial patellofemoral ligament (MPFL) on a virtual true lateral radiograph reconstructed from a three-dimensional computed tomography (3D-CT) image and (2) to compare this point with that of patients without patellofemoral instability and with Schöttle's point. METHODS: A total of 26 consecutive patients (29 affected knees) with recurrent patellar dislocation (RPD), who underwent MPFL reconstruction were included in this study (4 males; 22 females; mean age, 24.0 years old). Using a true lateral 3DCT image, the MPFL femoral insertion was identified and marked with a 2-mm circle, and this image was reconstructed as a virtual true lateral radiograph. Following Schöttle's method, the point of intersection was described by their anterior-posterior and proximal-distal positions. As a control population, 29 age- and gender-matched patients with anterior cruciate ligament (ACL) injuries were also analysed. RESULTS: The points in RPD patients were located significantly posterior (-2.5 ± 2.3 mm, p < 0.01) to the line representing an extension of the posterior cortex of the femur and distal (- 6.9 ± 2.4 mm, p < 0.01) to the posterior origin of the medial femoral condyle compared with those in the control population. The mean reference point of RPD patients was located in a 3.8-mm posterior and 4.4-mm distal position compared with Schöttle's point. CONCLUSIONS: An anatomical and radiographic femoral reference point of the MPFL on a true lateral virtual radiograph was described with our method. In patients with RPD, this reference point was identified to be more posterior and distal to Schöttle's point. More anatomical and individualized MPFL reconstruction will be secured using our method. LEVEL OF EVIDENCE: Level IV.

New standardization method of tibial tubercle-posterior cruciate ligament distance according to patient size in patients with patellofemoral instability.

BACKGROUND: Large differences in tibial tubercle-posterior cruciate ligament (TT-PCL) distance were described in several reports between countries, suggesting that abnormal TT-PCL distance is variable due to individual patient size. This study aimed to clarify the relationship between TT-PCL distance and patient size, and to determine a method for describing individualized TT lateralization. METHODS: We analyzed 41 patients with recurrent patellar dislocation (RPD) and 41 age-matched patients without patellar instability who underwent primary anterior cruciate ligament reconstruction (control). TT-PCL distance and tibia width (TW) were measured based on preoperative T2-weighted magnetic resonance imaging. Then, TT-PCL distance was standardized based on TW (TT-PCL ratio), and TT-PCL distance and ratio were compared between groups. Correlations were investigated among TT-PCL distance, TT-PCL ratio and each measurement (patient height, weight, TW). RESULTS: Strong positive correlations were observed between TW and patient height, and weak or moderate positive correlations were found between TT-PCL distance and each parameter. The mean TT-PCL distance was 21.2 and 20.6 mm (P = .39), while the mean TT-PCL ratio was 31.6% and 29.0% (P = .0093) in the RPD and control groups, respectively. The TT-PCL ratio was <34% in 39 of 41 knees (95.1%) in the control group. No correlation was indicated between the TT-PCL ratio and patient size. CONCLUSIONS: Our findings demonstrate that the TT-PCL ratio is not affected by patient size, although the TT-PCL distance is associated with knee size and patient height. The TT-PCL ratio could be an important index for identifying patients for whom distal realignment surgery should be considered.

Role of vasoactive intestinal peptide in the progression of osteoarthritis through bone sclerosis and angiogenesis in subchondral bone.

OBJECTIVE: Osteoarthritis (OA) is a progressive joint disorder, with abnormal remodeling of subchondral bone linked to the disruption of cartilage metabolism. Nerves also play an important role in bone remodeling in OA progression, and vasoactive intestinal peptide (VIP), one of the neuropeptides, plays an important role in bone metabolism. The aim of this study was to analyze the expression pattern of VIP in subchondral bone, and its potential as a therapeutic target for OA progression. DESIGN: The pattern of VIP expression in the human tibia was histologically evaluated. The effect of VIP on angiogenesis was investigated using human umbilical vein endothelial cells (HUVECs). Knee OA was induced by the resection of the medial meniscotibial ligament in C57BL/6 mice. A VIP receptor antagonist was intraperitoneally administered postoperatively, and therapeutic effects were analyzed at 4 and 8 weeks. RESULTS: VIP expression in the subchondral bone increased as OA progressed in human tibia. VIP was also expressed in the vascular channels into the cartilage layer. The total length and branch points were significantly increased, due to the VIP receptor agonist in HUVECs. In OA mice, the VIP receptor antagonist could prevent cartilage degeneration and subchondral bone sclerosis. The Osteoarthritis Research Society International score in the VIP receptor antagonist group was significantly lower than in the control group. CONCLUSION: VIP is involved in the progression of OA through its effect on subchondral bone sclerosis and angiogenesis. Inhibition of VIP signaling has the potential to be a therapeutic target to prevent OA progression.

Transplantation of autologous bone marrow-derived mesenchymal stem cells under arthroscopic surgery with microfracture versus microfracture alone for articular cartilage lesions in the knee: A multicenter prospective randomized control clinical trial.

INTRODUCTION: To investigate the efficacy of the transplantation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) under arthroscopy with microfracture (MFX) compared with microfracture alone. METHODS: Eleven patients with a symptomatic articular cartilage defect of the knee were included in the study. They were randomized to receive BMSCs with MFX (cell-T group, n=7) or MFX alone (control group, n=4). Clinical results were evaluated using International Knee Documentation committee (IKDC) knee evaluation questionnaires and the Knee Injury and Osteoarthritis Outcome Score (KOOS) before and 48 weeks after surgery. Quantitative and qualitative assessments of repair tissue were carried out at 48 weeks by T2 mapping of magnetic resonance images (MRIs) and the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system with follow-up MRI. RESULTS: No significant differences between preoperative and postoperative IKDC and KOOS were observed in the cell-T or control group. However, forty-eight weeks after surgery, the cell-T group showed a trend for a greater KOOS QOL score compared with the control group (79.4 vs. 39.1, respectively; P=0.07). The T2 value did not differ significantly between the two groups, but the mean MOCART score was significantly higher in the cell-T group than in the control group (P=0.02). CONCLUSIONS: Compared with MFX alone, BMSC transplantation with MFX resulted in better postoperative healing of the cartilage and subchondral bone as determined by the MOCART score. Clinically, BMSC transplantation with MFX gave a higher KOOS QOL score after 48 weeks.