Objectives. Articular cartilage damage is a primary outcome of pre-clinical and clinical studies evaluating meniscal and cartilage repair or replacement techniques. Recent studies have quantitatively characterized India Ink stained cartilage damage through light reflectance and the application of local or global thresholds. We develop a method for the quantitative characterisation of inked cartilage damage with improved generalisation capability, and compare its performance to the threshold-based baseline approach against gold standard labels. Methods. The Trainable WEKA Segmentation (TWS) tool (Arganda-Carreras et al., 2017) available in Fiji (Rueden et al., 2017) was used to train two separate Random Forest classifiers to automatically segment cartilage damage on ink stained cadaveric ovine stifle joints. Gold standard labels were manually annotated for the training, validation and test datasets for each of the femoral and tibial classifiers. Each dataset included a sample of medial and lateral femoral condyles and tibial plateaus from various stifle joints, selected to ensure no overlap across datasets according to ovine identifier. Training was performed on the training data with the TWS tool using edge, texture and noise reduction filters selected for their suitability and performance. The two trained classifiers were then applied to the validation data to output damage probability maps, on which a threshold value was calibrated. Model predictions on the unseen test set were evaluated against the gold standard labels using the Dice Similarity Coefficient (DSC) – an overlap-based metric, and compared with results for the baseline global threshold approach applied in Fiji as shown in Figures 1 and 2. Results. Test set results for the global threshold approach against gold standard labels were 45.0% DSC for the femoral condyle and 32.0% DSC for the tibial plateau. Results for the developed TWS classifiers on the same unseen test data were 79.0% and 72.7% DSC, showing absolute gains of 34.0% and 40.7% DSC over the global threshold baseline for the femoral and tibial classifiers. The trained TWS classifiers were then applied to an external set of unlabelled images of ink stained femoral condyles and tibial plateaus. Model results on sample images shown in Figure 3 further highlight the generalisation capability of the developed models. The most prominent classification features were Hessian filters (32.9%), Entropy (19.4%), Gaussian blur (10.1%), Gabor filters (6.3%) and Sobel filters (6.0%), with all other features contributing less than 6%. Conclusions. Our findings show that the developed segmentation method more accurately quantifies cartilage damage and provides improved generalisation capability over a range of input variations such as inconsistent orientation and lighting conditions. The developed model enables the use of articular cartilage damage as a reliable and quantitative outcome measure in studies involving large datasets, with reduced requirements for complex pre-processing and specialised equipment. For any figures or tables, please contact the authors directly

Meniscal root tears can result from traumatic injury to the knee or gradual degeneration. When the root is injured, the meniscus becomes de-functioned, resulting in abnormal distribution of hoop stresses, extrusion of the meniscus, and altered knee kinematics. If left untreated, this can cause articular cartilage damage and rapid progression of osteoarthritis. Multiple repair strategies have been described; however, no best fixation practice has been established. To our knowledge, no study has compared suture button, interference screw, and HEALICOIL KNOTLESS fixation techniques for meniscal root repairs. The goal of this study is to understand the biomechanical properties of these fixation techniques and distinguish any advantages of certain techniques over others. Knowledge of fixation robustness will aid in surgical decision making, potentially reducing failure rates, and improving clinical outcomes. 19 fresh porcine tibias with intact medial menisci were randomly assigned to four groups: 1) native posterior medial meniscus root (PMMR) (n = 7), 2) suture button (n = 4), 3) interference screw (n = 4), or 4) HEALICOIL KNOTLESS (n = 4). In 12 specimens, the PMMR was severed and then refixed by the specified group technique. The remaining seven specimens were left intact. All specimens underwent cyclic loading followed by load-to-failure testing. Elongation rate; displacement after 100, 500, and 1000 cycles; stiffness; and maximum load were recorded. Repaired specimens had greater elongation rates and displacements after 100, 500, and 1000 cycles than native PMMR specimens (p 0.05). The native PMMR showed greater maximum load than all repair techniques (p 0.05). In interference screw and HEALICOIL KNOTLESS specimens, failure occurred as the suture was displaced from the fixation and tension was gradually lost. In suture button specimens, the suture was either displaced or completely separated from the button. In some cases, tear formation and partial failure also occurred at the meniscus luggage tag knot. Native PMMR specimens failed through meniscus or meniscus root tearing. All fixation techniques showed similar biomechanical properties and performed inferiorly to the native PMMR. Evidence against significant differences between fixation techniques suggests that the HEALICOIL KNOTLESS technique may present an additional option for fixation in meniscal root repairs. While preliminary in vitro evidence suggests similarities between fixation techniques, further research is required to determine if clinical outcomes differ

Introduction. Post-meniscectomy syndrome is broadly characterised by intractable pain following the partial or total removal of a meniscus. There is a large treatment gap between the first knee pain after meniscectomy and the eligibility for a TKA. Hence, there is a strong unmet need for a solution that will relieve this post-meniscectomy pain. Goal of this first-in-man study was to evaluate the safety and performance of an anatomically shaped artificial medial meniscus prosthesis and the accompanying surgical technique. Methods. A first-in-man, prospective, multi-centre, single arm clinical investigation was intended to be performed on 18 post-medial meniscectomy syndrome patients with limited underlying cartilage damage (Kellgren Lawrence scale 0–3) in the medial compartment and having a normal lateral compartment. Eventually 5 patients received a polycarbonate urethane mediale meniscus prosthesis (Trammpolin® medial meniscus prosthesis; ATRO Medical B.V., the Netherlands) which was clicked onto two titanium screws fixated at the native horn attachments on the tibia. PROMs were collected at baseline and at 6 weeks, 3, 6, 12 and 24 months following the intervention including X-rays at 6, 12 and 24 Months. MRI scans were repeated after 12 and 24 months. Results. The surgical technique to select the appropriately sized implant and correct positioning of the fixation screws and meniscus prosthesis onto the tibia was demonstrated feasible and reproducible. The surgeries showed that in particular the positioning of the posterior screw is crucial for correct positioning of the prosthesis. Inclusion stopped after 5 patients, who reached the 6 months evaluation. The PROMs did not improve in the first 6 months after surgery. All patients reported knee joint stiffness and slight effusion in their knee at 6 months follow-up. In case of symptomatic patients an evaluation of the device position and integrity was performed by MRI. In three patients the implants were removed because of implant failure and in one patient the implant was removed because of persistent pain and extension deficit. At present one patient has the implant still in situ. The explantations of the implants demonstrated no articular cartilage damage and the fixation screws were securely anchored. Discussion. This is the first clinical study with an artificial meniscus-like prosthesis. Except one, all implants were removed due to implant breakage or discomfort of the patient. Analysis of the torn implants showed fatigue failure resulting from the lack of loadsharing between implant and cartilage: the implant was too stiff and carried all the load in the medial compartment of the knee. Furthermore, the fixation with screws seemed too rigid which restricted the motion of the posterior horn. Based on previous in vitro and animal experiments, we expected more creep of the material and more motion on the screw fixation. Conclusion. This first-in-man clinical study demonstrates that the investigated device design is not safe and did not perform as expected. Therefore, modification of the meniscus prosthesis design and fixation technique is required to allow for more motion of the meniscus prosthesis during knee joint movement

Aberrant infrapatellar fat metabolism is a notable feature provoking inflammation and fibrosis in the progression of osteoarthritis (OA). Irisin, a secretory subunit of fibronectin type III domain containing 5 (FNDC5) regulate adipose morphogenesis, energy expenditure, skeletal muscle, and bone metabolism. This study aims to characterize the biological roles of Irisin signaling in an infrapatellar fat formation and OA development. Injured articular specimens were harvested from 19 patients with end-stage knee OA and 11 patients with the femoral neck fracture. Knee joints in mice that overexpressed Irisin were subjected to intra-articular injection of collagenase to provoke OA. Expressions of Irisin, adipokines, and MMPs probed with RT-quantitative PCR. Infrapatellar adiposity, articular cartilage damage, and synovial integrity verified with histomorphometry and immunohistochemistry. Infrapatellar adipose and synovial tissues instead of articular cartilage exhibited Irisin immunostaining. Human OA specimens showed 40% decline in Irisin expression than the non-OA group. In vitro, the gain of Irisin function enabled synovial fibroblasts but not chondrocytes to display minor responses to the IL-1β provocation of MMP3 and MMP9 expression. Of note, Irisin signaling reduced adipogenic gene expression and adipocyte formation of mesenchymal progenitor cells. In collagenase-mediated OA knee pathogenesis, forced FNDC5 expression in articular compromised the collagenase-induced infrapatellar adipose hypertrophy, synovial hypercellularity, and membrane hyperplasia. These adipose-regulatory actions warded off the affected knees from cartilage destruction and gait aberrance. Likewise, intra-articular injection of Irisin recombinant protein mitigated the development of infrapatellar adiposity and synovitis slowing down the progression of cartilage erosion and walking profile irregularity. Affected joints and adipocytes responded to the Irisin recombinant protein treatment by reducing the expressions of cartilage-deleterious adipokines IL-6, leptin, and adiponectin through regulating PPAR&gamma, function. Irisin dysfunction is relevant to the existence of end-stage knee OA. Irisin signaling protects from excessive adipogenesis of mesenchymal precursor cells and diminished inflammation and cartilage catabolism actions aggravated by adipocytes and synovial cells. This study sheds emerging new light on the Irisin signaling stabilization of infrapatellar adipose homeostasis and the perspective of the therapeutic potential of Irisin recombinant protein for deescalating knee OA development

The zonal organization of articular cartilage is crucial in providing the tissue with mechanical properties to withstand compression and shearing force. Current treatments available for articular cartilage injury are not able to restore the hierarchically organized architecture of the tissue. Implantation of zonal chondrocyte as a multilayer tissue construct could overcome the limitation of current treatments. However, it is impeded by the lack of efficient zonal chondrocyte isolation protocol and dedifferentiation of chondrocytes during expansion on tissue culture plate (TCP). This study aims to develop a protocol to produce an adequate number of high-quality zonal chondrocytes for clinical application via size-based zonal chondrocyte separation using inertial spiral microchannel device and expansion under dynamic microcarrier culture. Full thickness (FT) chondrocytes isolated from porcine femoral condyle cartilage were subjected to two serial of size-based sorting into three subpopulations of different cell sizes, namely small (S1), medium (S2), and large (S3) chondrocytes. Zonal phenotype of the three subpopulations was characterised. To verify the benefit of stratified zonal chondrocyte implantation in the articular cartilage regeneration, a bilayer hydrogel construct composed of S1 chondrocytes overlaying a mixture of S2 and S3 (S2S3) chondrocytes was delivered to the rat osteochondral defect model. For chondrocyte expansion, two dynamic microcarrier cultures, sort-before-expansion and sort-after-expansion, which involved expansion after or before zonal cells sorting, were studied to identify the best sort-expansion strategy. Size-sorted zonal chondrocytes showed zone-specific characteristics in qRT-PCR with a high level of PRG4 expression in S1 and high level of aggrecan, Type II and IX collagen expression in S2 and S3. Cartilage reformation capability of sorted zonal chondrocytes in three-dimensional fibrin hydrogel showed a similar trend in qRT-PCR, histology, extracellular matrix protein quantification and mechanical compression test, indicating the zonal characteristics of S1, S2 and S3 as superficial (SZ), middle (MZ) and deep (DZ) zone chondrocytes, respectively. Implantation of bilayered zonal chondrocytes resulted in better cartilage tissue regeneration in a rat osteochondral defect model than FT control group, with predominantly Type II hyaline cartilage tissue and significantly lower Type I collagen. Dynamic microcarrier expansion of sorted zonal chondrocytes was able to retain the zonal cell size difference that correlate to zonal phenotype, while maintaining the rounded chondrocyte morphology and F-actin distribution similar to that in mature articular cartilage. With the better retention of zonal cell size and zonal phenotype relation on microcarrier, zonal cells separation was achievable in the sort-after-expansion strategy with cells expanded on microcarrier, in comparison to cells expanded on TCP. Inertial spiral microchannel device provides a label-free and high throughput method to separate zonal chondrocytes based on cell size. Stratified implantation of zonal chondrocytes has the potential to improve articular cartilage regeneration. Dynamic microcarrier culture allows for size-based zonal chondrocyte separation to be performed on expanded chondrocytes, thus overcoming the challenge of limited tissue availability from the patients. Our novel zonal chondrocyte isolation and expansion protocol provide a translatable strategy for stratified zonal chondrocyte implantation that could improve articular cartilage regeneration of critical size defects

Background. Cam-type femoro-acetabular impingement (FAI) is increasingly recognised as a cause of mechanical hip symptoms in young adults. It is likely that it is a cause of early hip degeneration. Ganz et al have developed a therapeutic procedure involving trochanteric flip osteotomy and dislocation of the hip, and have reported good results. We have developed an arthroscopic osteochondroplasty to reshape the proximal femur and relieve impingement. Methods. Fifty patients who presented with mechanical hip symptoms and had demonstrable cam-type FAI on radially-reconstructed MR arthrography, were treated by arthroscopic osteochondroplasty. Ten patients had a post-operative CT; from these images flexion and internal rotation range was tested in a virtual reality (VR) model to determine adequacy of resection. All patients were followed up for a minimum of one year, and post-operative Non-Arthritic Hip Scores (NAHS, maximum possible score 100) compared with pre-operative NAHS. Results. Mean operating time was 110 minutes. 31 patients were discharged on the day of surgery, the remainder on the following day. There were no complications. All patients were asked to be partially weight-bearing with crutches for four weeks but most returned to work within two weeks. The VR models showed satisfactory resection, although there was clear evidence of improved precision with practice. Symptoms improved in all but two patients, with mean NAHS improving from 54 pre-operatively to 87 at one year. The two patients who did not improve, were both found to have unexpectedly extensive acetabular articular cartilage damage. Conclusion. Arthroscopic femoral reshaping to relieve FAI is feasible, safe and reliable. However it is technically difficult and time-consuming. The results are comparable to open dislocation and debridement, but the arthroscopic procedure avoids the prolonged disability and the complications associated with trochanteric flip osteotomy

Chondral damage within the knee commonly occurs during sport following direct trauma or following degeneration through overuse. Radio frequency energy chondroplasty (RFC) can be used as an alternative to mechanical chondroplasty in the arthroscopic treatment of chondral lesions. Current literature supports the theoretical advantage of RFC and purports to in vitro improvements in cartilage structure and function following RFC. We conducted a retrospective study of patients undergoing RFC for isolated chondral lesions in the knee and assessed the short term clinical benefits. Retrospective analysis was completed of operative notes and arthroscopic images of all patients who underwent arthroscopic chondroplasty at the royal Devon and Exeter Hospital between January 2009 and June 2012. Inclusion criteria included 1 to 2 defined chondral lesions, less than 2cm2, of Outerbridge grade II-IV, treated via arthroscopic RFC. Exclusion criteria included diffuse articular cartilage damage, additional pathologies affecting the knee or subsequent further injuries or invasive procedures to the knee. Data was collected via a subjective and objective questionnaire assessing patient outcome. 35 patients met the inclusion criteria, 32 were successfully followed up. Male: female ratio was 16:16, with a mean age of 39.5 (range 19–60). 84% (n=27) of patients experienced a significant reduction in pain (mean reduction of 51%, p < 0.001) lasting until the time of study (median of 21 months, range 9 to 31 months). There was no correlation between change in symptoms and site and grade of chondral lesion. Pre-operative instability symptoms did not significantly improve following RFC. Satisfaction with treatment was in direct correlation with pain relief achieved. Our study appears to support current literature by suggesting short term improvements to pain following the use of RFC on chondral lesions. Greater population size and longer follow-up are required to provide more significant conclusions

Hyaline articular cartilage has been known to be a troublesome tissue to repair once damaged. Since the introduction of autologous chondrocyte implantation (ACI) in 1994, a renewed interest in the field of cartilage repair with new repair techniques and the hope for products that are regenerative have blossomed. This article reviews the basic science structure and function of articular cartilage, and techniques that are presently available to effect repair and their expected outcomes.