Meniscus tears have been treated using partial meniscectomy to relieve pain in patients, although this leads to the onset of early osteoarthritis (OA). Cell-based therapies can help preserve the meniscus, although the presence of inflammatory cytokines compromises clinical outcomes. Anti-inflammatory drugs (e.g. celecoxib), can help to reduce pain in patients and in vitro studies suggest a beneficial effect on cytokine inhibited matrix content. Previously, we have demonstrated that the inhibitory effects of IL-1β can be countered by culture under low oxygen tension or physioxia. The present study sought to understand whether physioxia, celecoxib or combined application can counter the inhibitory effects IL-1β inhibited meniscus cells. Human avascular and vascular meniscus cells (n =3) were isolated and expanded under 20% (hyperoxia) or 2% (physioxia) oxygen. Cells were seeded into collagen scaffolds (Geistlich, Wolhusen) and cultured for 28 days either in the presence of 0.1ng/mL IL-1β, 5µg/mL celecoxib or both under their expansion oxygen conditions. Histological (DMMB, collagen I and collagen II immunostaining), GAG content and gene expression analysis was evaluated for the scaffolds. Under hyperoxia, meniscus cells showed a significant reduction in GAG content in the presence of IL-1β (*p < 0.05). Celecoxib alone did not significantly increase GAG content in IL-1β treated cultures. In contrast, physioxic culture showed a donor dependent increase in GAG content in control, IL-1β and celecoxib treated cultures with corresponding histological staining correlating with these results. Additionally, gene expression showed an upregulation in COL1A1, COL2A1 and ACAN and a downregulation in MMP13 and ADAMTS5 under physioxia for all experimental groups. Physioxia alone had a stronger effect in countering the inhibitory effects of IL-1β treated meniscus cells than celecoxib under hyperoxia. Preconditioning meniscus cells under physioxia prior to implantation has the potential to improve clinical outcomes for cell-based therapies of the meniscus

Meniscus tears in adult patients do not heal spontaneously and represent a risk factor for OA development. PDGF is well known as an enhancer of meniscal cell biosynthetic activity and also has chemotactic activity for mesenchymal cells. PDGF incorporation into scaffolds should be efficient for recruitment of cells to initiate repair in the injured meniscus. We recently developed decellularized meniscus sheet for use in the treatment of meniscus tears. The aim of this study is to examine the potential of PDGF-coated decellularized meniscus scaffold in mediating integrative healing by endogenous cell migration. Fresh bovine meniscus was chemically decellularized. Round sheets were made from the decellularized tissue. Heparin was covalently conjugated with decellularized meniscus scaffold (DMS). PDGF-BB was immobilized by binding to the heparin-conjugated DMS. In vitro, PDGF release kinetics was analyzed by ELISA. DMS was transplanted into the injured meniscus explants and cultured for 2 and 4 weeks. The numbers of migrated cells at the border between DMS and injured explant were counted on DAPI stained sections and PDGFRb expressing cells were counted after immunohistochemical staining. The newly produced ECM and collagen fiber alignment was detected by histology on Safranin-O and picrosirius red stained sections. The explants were also tested for tensile properties. PDGF release kinetics showed sustained slow release in heparin-conjugated DMS, with 11.2% release at day- 16th compared to 26.1% release from the DMS without heparin. Insertion of the PDGF-treated DMS into the meniscus tears in bovine meniscus explants led to the migration of endogenous meniscus cells to the defect zone. The migrated cells expressed PDGFRb and produced new ECM in the defect area. Safranin-O and pircrosirius red staining showed tissue integration between DMS and injured explants. Moreover, the higher concentration of PDGF promoted cell integration into the DMS. Tensile properties of injured explants treated with PDGF coated DMS were significantly higher than in DMS without PDGF. Heparin-conjugated DMS showed strong immobilization of PDGF, which was released slowly. PDGF coated DMS promoted migration of endogenous meniscus cells to the defect area and into the scaffold. New matrix was formed that bridged the space between the native meniscus and the scaffold and this was associated with improved biomechanical properties. The PDGF coated DMS is a novel, feasible and efficient approach for the treatment of meniscus tears

Aims. To fully quantify the effect of posterior tibial slope (PTS) angles on joint kinematics and contact mechanics of intact and anterior cruciate ligament-deficient (ACLD) knees during the gait cycle. Methods. In this controlled laboratory study, we developed an original multiscale subject-specific finite element musculoskeletal framework model and integrated it with the tibiofemoral and patellofemoral joints with high-fidelity joint motion representations, to investigate the effects of 2.5° increases in PTS angles on joint dynamics and contact mechanics during the gait cycle. Results. The ACL tensile force in the intact knee was significantly affected with increasing PTS angle. Considerable differences were observed in kinematics and initial posterior femoral translation between the intact and ACLD joints as the PTS angles increased by more than 2.5° (beyond 11.4°). Additionally, a higher contact stress was detected in the peripheral posterior horn areas of the menisci with increasing PTS angle during the gait cycle. The maximum tensile force on the horn of the medial meniscus increased from 73.9 N to 172.4 N in the ACLD joint with increasing PTS angles. Conclusion. Knee joint instability and larger loading on the medial meniscus were found on the ACLD knee even at a 2.5° increase in PTS angle (larger than 11.4°). Our biomechanical findings support recent clinical evidence of a high risk of failure of ACL reconstruction with steeper PTS and the necessity of ACL reconstruction, which would prevent meniscus tear and thus the development or progression of osteoarthritis. Cite this article: Bone Joint Res 2022;11(10):739–750

Aims. Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect. Methods. A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus. Results. In vitro immunohistochemistry revealed that the meniscus cells migrated from the minced meniscus and proliferated in the gel. Furthermore, histological analysis suggested that the minced meniscus embedded in the atelocollagen gel produced tissue resembling the native meniscus in vivo. The minced meniscus group also had a higher Pauli’s score compared to the defect and atelocollagen groups. Conclusion. Our data show that cells in minced meniscus can proliferate, and that implantation of the minced meniscus within atelocollagen induces meniscus regeneration, thus suggesting a novel therapeutic alternative for meniscus tears. Cite this article: Bone Joint Res 2021;10(4):269–276

Discoid meniscus (DM) is a congenital variant of the knee joint that involves morphological and structural deformation, with potential meniscal instability. The prevalence of the Discoid Lateral Meniscus (DLM) is higher among the Asians than among other races, and both knees are often involved. Meniscal pathology is widely prevalent in the adult population, secondary to acute trauma and chronic degeneration. The true prevalence in children remains unknown, as pathologies such as discoid menisci often go undiagnosed, or are only found incidentally. A torn or unstable discoid meniscus can present with symptoms of knee pain, a snapping or clicking sensation and/or a decrease in functional activity, although it is not known if a specific presentation is indicative of a torn DM. While simple radiographs may provide indirect signs of DLM, magnetic resonance imaging (MRI) and arthroscopy is essential for diagnosis and treatment planning. Asymptomatic patients require close follow-up without surgical treatment, while patients with symptoms often require surgery. Partial meniscectomy is currently considered the treatment of choice for DLM. For children are more likely to achieve better results after partial meniscectomy

Prospectively, we determined amount of meniscus loss and anatomic location of Collagen Meniscus Implant (CMI) placement after partial medial meniscectomy (PMM). At 1-year relook we determined total meniscus tissue present based on surface area coverage. We correlated percent of meniscus and anatomic location of the original lesion with function and activity levels 6 years after CMI placement. We hypothesized that meniscus amount and anatomic location would influence clinical function and activity levels. In a prospective randomized controlled multicenter clinical trial (Level of Evidence I), 114 chronic patients (1 to 3 prior PMM on the involved meniscus) 18 to 60 years old underwent partial medial meniscectomy, and then randomly one group received a CMI to fill the meniscus defect. There were 68 PMM only controls and 46 CMI patients. At index surgery, amount and anatomic location of meniscus removed and CMI placement were documented on a standard grid. Locations were categorized as posterior (A), middle (B), or anterior (C) third. A 1-year relook was done on CMI patients, and meniscus surface area coverage was measured. Patients were followed clinically for a minimum of two years and subjectively annually thereafter. Average follow-up was 69 months (range, 24 to 92). All patients completed validated questionnaires including Lysholm and Tegner scores to assess function and activity. For CMI patients, 29 had lesions which included posterior and middle thirds (AB), and 17 had lesions involving all three zones (ABC). Lysholm scores were significantly higher in patients with AB lesions (81) compared to ABC lesions (71), p=0.046. AB lesion patients also had significantly higher Tegner index (0.70) than ABC lesion patients (0.22), thus AB patients regained more of their lost activity, p=0.049. Comparing all patients with > 60% meniscus surface area coverage, CMI patients had significantly higher Tegner index compared to controls (0.59 vs. 0.30), p=0.036. No differences between treatment groups were seen in patients with < 60% meniscus surface area coverage. When comparing 24 month to final follow-up values, controls had no change for Lysholm (p=0.13) or Tegner (p=0.39) scores, but CMI patients improved significantly over time for both Lysholm (p=0.02) and Tegner (p=0.04) scores. Zones of meniscus involvement influenced clinical outcomes at 6 years in CMI patients. Those whose lesions extended into all three zones did worse than those with lesions in posterior and middle zones only. Patients with successful CMI procedures yielding > 60% meniscus surface area coverage were significantly better than PMM only controls for both clinical function and activity levels. Noteworthy, CMI patients continue to improve over time for clinical function and activity levels, but PMM controls do not

Aims. Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA. Methods. We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs. Results. During OA, there were 626, 97, 1,060, and 2,330 differentially expressed genes in articular cartilage, meniscus, synovium, and subchondral bone, respectively. Gene Ontology enrichment revealed that these genes were enriched in extracellular matrix and structure organization, ossification, neutrophil degranulation, and activation at different degrees. Through ligand-receptor pairing and proteome of OA synovial fluid, we predicted ligand-receptor interactions and constructed a crosstalk atlas of the whole joint. Several interactions were reproduced by transwell experiment in chondrocytes and synovial cells, including TNC-NT5E, TNC-SDC4, FN1-ITGA5, and FN1-NT5E. After lipopolysaccharide (LPS) or interleukin (IL)-1β stimulation, the ligand expression of chondrocytes and synovial cells was upregulated, and corresponding receptors of co-culture cells were also upregulated. Conclusion. Each tissue displayed a different expression pattern in transcriptome, demonstrating their specific roles in OA. We highlighted tissue molecular crosstalk through ligand-receptor pairs in OA pathophysiology, and generated a crosstalk atlas. Strategies to interfere with these candidate ligands and receptors may help to discover molecular targets for future OA therapy. Cite this article: Bone Joint Res 2022;11(12):862–872

Abstract. Aims. We studied the outcomes following arthroscopic primary repair of bucket handle meniscus tears to determine the incidence of re-tears and the functional outcomes of these patients. Methodology. Prospective cohort study. Over a 4-year period (2016 to 2020), 35 adult patients presented with a bucket handle tear of the meniscus. Arthroscopic meniscal repair was performed using either the all inside technique or a combination of all-inside and inside-out techniques. 15 patients also underwent simultaneous arthroscopic anterior cruciate ligament reconstruction. Functional knee scores were assessed using IKDC and Lysholm scores. Results. Mean patient age at surgery was 27 years (range, 17 to 53years). Medial meniscus was torn in 20 and lateral in 15 cases. Zone of tear was white on white in 19, red on white in 9 and red on red in 7 cases. Average delay from injury to surgery was 4 months. At a mean follow-up of 4.5 years, the meniscus repair failed in 3 patients (8.5 %). Outcome following re-tear was meniscus excision. Average IKDC scores in patients with intact repair were 74.04 against 56.67 in patients with a failed repair (p< 0.0001). Similarly, Lyshlom scores were 88.96 and 67.333, respectively (p<0.0001). Conclusion. The survivorship of primary repair of bucket handle meniscus tears in our series was 91.5% at medium term follow-up. Functional outcomes were significantly poor in patients with a failed repair compared to those with an intact repair

Aims. We studied the outcomes following arthroscopic primary repair of bucket handle meniscus tears to determine the incidence of re-tears and the functional outcomes of these patients. Methodology. Prospective cohort study. Over a 4-year period (2016 to 2020), 35 adult patients presented with a bucket handle tear of the meniscus. Arthroscopic meniscal repair was performed using either the all inside technique or a combination of all-inside and inside-out techniques. 15 patients also underwent simultaneous arthroscopic anterior cruciate ligament reconstruction. Functional knee scores were assessed using IKDC and Lysholm scores. Results. Mean patient age at surgery was 27 years (range, 17 to 53years). Medial meniscus was torn in 20 and lateral in 15 cases. Zone of tear was white on white in 19, red on white in 9 and red on red in 7 cases. Average delay from injury to surgery was 4 months. At a mean follow-up of 4.5 years, the meniscus repair failed in 3 patients (8.5 %). Outcome following re-tear was meniscus excision. Average IKDC scores in patients with intact repair were 74.04 against 56.67 in patients with a failed repair (p< 0.0001). Similarly, Lyshlom scores were 88.96 and 67.333, respectively (p<0.0001). Conclusion. The survivorship of primary repair of bucket handle meniscus tears in our series was 91.5% at medium term follow-up. Functional outcomes were significantly poor in patients with a failed repair compared to those with an intact repair

Aims. Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease. Methods. A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed. Results. A total of 161 studies were included, which covered capsule, ligaments, meniscus, skeletal muscle, synovium, and tendon in both humans and animals, and fat pad and intervertebral disc in humans only. These studies covered a wide variety of ECM features, including individual ECM components (i.e. collagens, proteoglycans, and glycoproteins), ECM architecture (i.e. collagen fibre organization and diameter), and viscoelastic properties (i.e. elastic and compressive modulus). Some ECM changes, notably calcification and the loss of collagen fibre organization, have been extensively studied across osteoarthritic tissues. However, most ECM features were only studied by one or a few papers in each tissue. When comparisons were possible, the results from animal experiments largely concurred with those from human studies, although some findings were contradictory. Conclusion. Changes in ECM composition and architecture occur throughout non-cartilage soft tissues in the osteoarthritic joint, but most of these remain poorly defined due to the low number of studies and lack of healthy comparator groups. Cite this article: Bone Joint Res 2024;13(12):703–715

Aims. Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA. Methods. First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers. Results. C1 subtype is mainly concentrated in the development of skeletal muscle organs, C2 lies in metabolic process and immune response, and C3 in pyroptosis and cell death process. Therefore, we divided OA into three subtypes: bone remodelling subtype (C1), immune metabolism subtype (C2), and cartilage degradation subtype (C3). The number of macrophage M0 and activated mast cells of C2 subtype was significantly higher than those of the other two subtypes. COL2A1 has significant differences in different subtypes. The expression of COL2A1 is related to age, and trafficking protein particle complex subunit 2 is related to the sex of OA patients. Conclusion. This study linked different tissues with gene expression profiles, revealing different molecular subtypes of patients with knee OA. The relationship between clinical characteristics and OA-related genes was also studied, which provides a new concept for the diagnosis and treatment of OA. Cite this article: Bone Joint Res 2023;12(12):702–711

Objectives. Meniscal injuries are often associated with an active lifestyle. The damage of meniscal tissue puts young patients at higher risk of undergoing meniscal surgery and, therefore, at higher risk of osteoarthritis. In this study, we undertook proof-of-concept research to develop a cellularized human meniscus by using 3D bioprinting technology. Methods. A 3D model of bioengineered medial meniscus tissue was created, based on MRI scans of a human volunteer. The Digital Imaging and Communications in Medicine (DICOM) data from these MRI scans were processed using dedicated software, in order to obtain an STL model of the structure. The chosen 3D Discovery printing tool was a microvalve-based inkjet printhead. Primary mesenchymal stem cells (MSCs) were isolated from bone marrow and embedded in a collagen-based bio-ink before printing. LIVE/DEAD assay was performed on realized cell-laden constructs carrying MSCs in order to evaluate cell distribution and viability. Results. This study involved the realization of a human cell-laden collagen meniscus using 3D bioprinting. The meniscus prototype showed the biological potential of this technology to provide an anatomically shaped, patient-specific construct with viable cells on a biocompatible material. Conclusion. This paper reports the preliminary findings of the production of a custom-made, cell-laden, collagen-based human meniscus. The prototype described could act as the starting point for future developments of this collagen-based, tissue-engineered structure, which could aid the optimization of implants designed to replace damaged menisci. Cite this article: G. Filardo, M. Petretta, C. Cavallo, L. Roseti, S. Durante, U. Albisinni, B. Grigolo. Patient-specific meniscus prototype based on 3D bioprinting of human cell-laden scaffold. Bone Joint Res 2019;8:101–106. DOI: 10.1302/2046-3758.82.BJR-2018-0134.R1

Purpose: The collagen meniscus implant (CMI, Sulzer) is a meniscal substitute with a collagen matrix serving as a tutor for autologous regeneration of meniscal tissue. The goal is to prevent mid-term degradation after meniscectomy. The CMI is inserted arthroscopically. The purpose of this multicentric European study was to verify the safety, technical feasibility, and short-term clinical efficacy of the CMI in a population of patients undergoing medial meniscectomy. The long-term results should be obtained within a delay of five years at least. Material and results: The series included patients with medial meniscus lesions alone, with or without lesions of the anterior cruciate ligament (present in 44% of the patients and repaired at the same time). Patient consent was obtained in all cases (in France in accordance with the Huriet law). Patients with lesions of the lateral ligament, associated trade IV cartilage lesions, or lesions of the posterior cruciate ligament were excluded. The study included 98 patients, mean age 33 years. Four patients were excluded from the analysis due to complications. Currently, 66 patients are available for evaluation one year after insertion of the CMI. Subjective outcome, the Lysholm score, and x-ray and MRI findings were recorded. Evaluation up to five years follow-up is scheduled. Results: Complications: There were four early complications: infectious arthritis (n=1), puriform arthritis without germ (n=2), implant rupture (n=1). There were no implant-related postop complications. Clinical results: At one year follow-up, the Lysholm score was 97. Pain was mild (1 on the visual analogue scale) and was only observed in one out of six patients: 87% of the patients had a normal or nearly normal knee. Radiological results: There were no radiological signs of early degeneration. It was difficult to interpret the MRI results which visualised a structure with an intermediary signal in the form of a meniscal triangle. MRI did on show any sign of deleterious effect on the neighbouring cartilage. Discussion: This technique for replacing the meniscus is an alternative to allogenic grafting. These preliminary results must of course be interpreted with caution. They show that arthroscoic implantation of the CMI is feasible but difficult. There was no evidence of an immunological reaction. Complications were related to the operative difficulty. Clinical results were satisfactory at one year, particularly in terms of pain. On the other hand, the biomechanical value of the implant cannot be assessed until longer follow-up data becomes available. Conclusion: In light of the operative difficulty, the long postoperative recovery due to the rehabilitation protocol, the CMI should be used for symptomatic knees after meniscectomy, particularly in case of anterior laxity

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

Aims. This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA). Methods. Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model. Results. We discovered for the first time that MCL was substantially enriched in the synovial fluid of OA patients and promoted the release of inflammatory cytokines from FLSs through MCL phagocytosis. Through LC‒MS, ANT3 was identified and determined to be significantly upregulated in MCL and OA-FLSs, corresponding to impaired mitochondrial function and cell viability in OA-FLSs. Mitochondrial homeostasis was restored by ANT3 suppression, thereby alleviating synovial inflammation. Furthermore, elevated ANT3 levels inhibited ERK phosphorylation. Specifically, silencing ANT3 prevented inhibition of ERK phosphorylation and significantly reduced the elevation of reactive oxygen species (ROS) and JC1 membrane potential in MCL-induced synovial inflammation. Conclusion. This study revealed the important roles of MCL and ANT3 in FLS mitochondria. Silencing ANT3 rescued ERK phosphorylation, thereby restoring mitochondrial homeostasis in FLSs and alleviating synovitis and OA development, offering a potential target for treating synovitis and preventing early-stage OA. Cite this article: Bone Joint Res 2023;12(4):274–284

Aims. To evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope. Methods. Based on sample size calculation, 70 male C57BL/6 mice were randomly assigned to three surgery groups: DMM aided by a stereomicroscope; DMM by naked eye; or sham surgery. The group information was blinded to researchers. Mice underwent static weightbearing, von Frey test, and gait analysis at two-week intervals from eight to 16 weeks after surgery. Histological grade of OA was determined with the Osteoarthritis Research Society International (OARSI) scoring system. Results. Surgical DMM with or without stereomicroscope led to decrease in the mean of weightbearing percentages (-20.64% vs -21.44%, p = 0.792) and paw withdrawal response thresholds (-21.35% vs -24.65%, p = 0.327) of the hind limbs. However, the coefficient of variation (CV) of weight-bearing percentages and paw withdrawal response thresholds in naked-eye group were significantly greater than that in the microscope group (19.82% vs 6.94%, p < 0.001; 21.85% vs 9.86%, p < 0.001). The gait analysis showed a similar pattern. Cartilage degeneration was observed in both DMM-surgery groups, evidenced by increased OARSI scores (summed score: 11.23 vs 11.43, p = 0.842), but the microscope group showed less variation in OARSI score than the naked-eye group (CV: 21.03% vs 32.44%; p = 0.032). Conclusion. Although surgical DMM aided by stereomicroscope is technically difficult, it produces a relatively more homogeneous OA model in terms of the discrete degree of pain behaviours and histopathological grading when compared with surgical DMM without stereomicroscope. Cite this article: Bone Joint Res 2022;11(8):518–527

Abstract. Objectives. Meniscus allograft and synthetic meniscus scaffold (Actifit. ®. ) transplantation have shown promising outcomes for symptoms relief in patients with meniscus deficient knees. Untreated chondral defects can place excessive load onto meniscus transplants and cause early graft failure. We hypothesised that combined ACI and allograft or synthetic meniscus replacement might provide a solution for meniscus deficient individuals with co-existing lesions in cartilage and meniscus. Methods. We retrospectively collected data from 17 patients (16M, 1F, aged 40±9.26) who had ACI and meniscus allograft transplant (MAT), 8 patients (7M, 1F, aged 42±11) who underwent ACI and Actifit. ®. meniscus scaffold replacement. Other baseline data included BMI, pre-operative procedures and cellular transplant data. Patients were assessed by pre-operative, one-year and last follow-up Lysholm score, one-year repair site biopsy, MRI evaluations. Results. In the MAT group, the final post-operative evaluation was 7±4.5 years. The mean pre-operative Lysholm score was 49±17, rose to 66.6±16.4 1 year post-op and dropped to 58±26 at final evaluation. Four of the 17 patients had total knee replacements (TKRs) at average 6.4 years after treatment. In the Actifit. ®. group, the final post-operative assessment was 5.6±2.7years. The pre-operative Lysholm score was 53.7±21.3, increasing to 72.8±15.2 at 1 year and 70.4±27.6 at final clinical follow-up. None of the patients in the Actifit® group had received TKRs. Conclusions. Both MAT and Actifit. ®. groups were effective in improving patients symptoms and knee function according to one-year post-operative assessments. However, the knee function of patients in MAT group dropped at final follow-up, whereas the Actifit® group maintained their knee function. These preliminary findings warrant further investigations, to include more patients and alongside comparisons to ACI alone and allograft/Actifit. ®. alone as comparator groups before accurate conclusions may be drawn on the comparative efficacy of each technique. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

The meniscus is comprised largely of type I collagen, as well as fibrochondrocytes and proteoglycans. In articular cartilage and intervertebral disc, proteoglycans make a significant contribution to mechanical stiffness of the tissue via negatively charged moieties which generate Donnan osmotic pressures. To date, such a role for proteoglycans in meniscal tissue has not been established. This study aimed to investigate whether meniscal proteoglycans contribute to mechanical stiffness of the tissue via electrostatic effects. Following local University Ethics Committee approval, discs of meniscal tissue two millimetres thick and of five millimetres diameter were obtained from 12 paired fresh frozen human menisci, from donors < 6 5 years of age, with no history of osteoarthritis or meniscal injury. Samples were taken from anterior, middle and posterior meniscal regions. Each disc was placed within a custom confined compression chamber, permeable at the top and bottom only and then bathed in one of three solutions − 0.14M PBS (mimics cellular environment), deionised water (negates effect of mobile ions) or 3M PBS (negates all ionic effects). The apparatus was mounted within a Bose Electroforce 3100 materials testing machine and a 0.3N preload was applied. The sample was allowed to reach equilibrium, before being subjected to a 10% ramp compressive strain followed by a 7200 second hold phase. Equal numbers of samples from each meniscus and meniscal region were tested in each solution. Resultant stress relaxation curves were fitted to a nonlinear poroviscoelastic model with strain dependent permeability using FEBio finite element modelling software. Goodness of fit (R2) was assessed using a coefficient of determination. All samples were assayed for proteoglycan content. Comparison of resultant mechanical parameters was undertaken using multivariate ANOVA with Bonferroni adjustment for multiple comparisons. 36 samples were tested. A significant difference (p < 0 .05) was observed in the value of the Young's modulus (E) between samples tested in deionised water compared to 0.14M/3M PBS, with the meniscus found to be stiffest in deionised water (E = 1.15 MPa) and least stiff in 3M PBS (E = 0.43 MPa), with the value of E in 0.14M PBS falling in between (0.68 MPa). No differences were observed in the zero strain permeability or the exponential strain dependent/stiffening coefficients. The viscoelastic coefficient and relaxation time values were not found to improve model fit and were thus held at zero. The mean R2 value was 0.78, indicating a good fit and did not differ significantly between solutions. Proteoglycan content was not found to differ with solution, but was found to be significantly increased in the middle region of both menisci. Proteoglycans make a significant electrostatic contribution to mechanical stiffness of the meniscus, increasing it by 58% in the physiological condition, and are hence integral to its function. It is important to include the influence of ionic effects when modelling meniscus, particularly where fluid flow or localised strain is modelled. From a clinical perspective, it is critical that meniscal regeneration strategies such as scaffolds or allografts attempt to preserve, or compensate for, the function of proteoglycans to ensure normal meniscal function

Recent findings have identified the importance of previously undiagnosed or neglected meniscus lesions in association with anterior cruciate ligament (ACL) injuries (e.g. medial meniscus ramp lesions and posterior root tears of the lateral meniscus). There is increasing biomechanical evidence that they bear the potential to alter both anteroposterior and rotational laxity patterns in ACL injured knees. Few data exist with respect to the presence of these specific tear entities in large series of ACL injured patients. The purpose of the study was to analyze the meniscus tear pattern in a series of ACL injured knees with a special focus on ramp lesions of the medial meniscus and posterior root lesions of the lateral meniscus. The hypothesis was that a significant number of ACL injured patients would display these types of lesions. Data from 358 patients undergoing an ACL reconstruction (227 males /131 females, age: 28±10) were extracted from a center-based registry. The type of ACL tear (partial versus complete) as well as the presence of associated meniscus lesions were documented. Meniscus lesions were classified into the following categories: medial ramp lesions, lateral root lesions, medial ramp and lateral root lesion, other medial meniscus injuries, other lateral meniscus injuries, other bimeniscal injuries. Chi-square tests were used to determine whether the percentage of meniscal lesions differed between types of ACL tear, gender and age (below 21, 21–35, above 35). Significance was set at p < 0.05. Isolated ACL tears were present in 107 (30%) of the operated knees (31 partial; 327 complete). Complete ACL lesions were more likely to present an associated meniscus injury (321 out of 327, 71%) than partial tears (13 out of 31, 42%). The incidence of meniscus injuries which are associated with ACL tears is very high (70%). Previously undiagnosed or neglected meniscus injuries like medial ramp or lateral root tears could be identified in 35% of patients. As such, the hypothesis was confirmed that an important amount of ACL injured knees display this specific intraarticular soft tissue damage. A systematic evaluation of these lesions under arthroscopy should thus be performed and specific repair needs to be evaluated