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Connective Tissue Research 2017Meniscus injury and treatment occurred with the majority of anterior cruciate ligament reconstructions (ACLR) in the multicenter orthopedic outcomes (MOON) cohort. We... (Review)
Review
Meniscus injury and treatment occurred with the majority of anterior cruciate ligament reconstructions (ACLR) in the multicenter orthopedic outcomes (MOON) cohort. We describe the patient-reported outcomes, radiographic outcomes, and predictors of pain from meniscus injuries and treatment in the setting of ACLR. Patient-reported outcomes improve significantly following meniscus repair with ACLR, but differences exist based on the meniscus injury laterally (medial or lateral). Patients undergoing medial meniscus repair have worse patient-reported outcomes and more pain compared to those with uninjured menisci. However, lateral meniscal tears can be repaired with similar outcomes as uninjured menisci. Medial meniscal treatment (meniscectomy or repair) results in a significant loss of joint space at 2 years compared to uninjured menisci. Menisci treated with excision had a greater degree of joint space loss compared to those treated with repair. Clinically significant knee pain is more common following injuries to the medial meniscus and increased in patients who undergo early re-operation after initial ACLR. Future research efforts aimed at improving outcomes after combined ACLR and meniscus treatment should focus on optimizing biologic and mechanical environments that promote healing of medial meniscal tears sustained during ACL injury.
Topics: Adolescent; Anterior Cruciate Ligament Reconstruction; Female; Follow-Up Studies; Humans; Male; Meniscus; Pain, Postoperative; Treatment Outcome
PubMed: 28282214
DOI: 10.1080/03008207.2017.1297808 -
Cell and Tissue Research Oct 2017The increasing rate of injuries to the meniscus indicates the urgent need to develop effective repair strategies. Irreparably damaged menisci can be replaced and... (Review)
Review
The increasing rate of injuries to the meniscus indicates the urgent need to develop effective repair strategies. Irreparably damaged menisci can be replaced and meniscus allografts represent the treatment of choice; however, they have several limitations, including availability and compatibility. Another approach is the use of artificial implants but their chondroprotective activities are still not proved clinically. In this situation, tissue engineering offers alternative natural decellularized extracellular matrix (ECM) scaffolds, which have shown biomechanical properties comparable to those of native menisci and are characterized by low immunogenicity and promising regenerative potential. In this article, we present an overview of meniscus decellularization methods and discuss their relative merits. In addition, we comparatively evaluate cell types used to repopulate decellularized scaffolds and analyze the biocompatibility of the existing experimental models. At present, acellular ECM hydrogels, as well as slices and powders, have been explored, which seems to be promising for partial meniscus regeneration. However, their inferior biomechanical properties (compressive and tensile stiffness) compared to natural menisci should be improved. Although an optimal decellularized meniscus scaffold still needs to be developed and thoroughly validated for its regenerative potential in vivo, we believe that decellularized ECM scaffolds are the future biomaterials for successful structural and functional replacement of menisci.
Topics: Animals; Biocompatible Materials; Extracellular Matrix; Humans; Hydrogels; Meniscus; Regeneration; Tissue Engineering; Tissue Scaffolds
PubMed: 28364144
DOI: 10.1007/s00441-017-2605-0 -
Journal of Biomechanics May 2021The meniscus is crucial in maintaining the knee function and protecting the joint from secondary pathologies, including osteoarthritis. Although most of the mechanical...
The meniscus is crucial in maintaining the knee function and protecting the joint from secondary pathologies, including osteoarthritis. Although most of the mechanical properties of human menisci have been characterized, to our knowledge, its dynamic shear properties have never been reported. Moreover, little is known about meniscal shear properties in relation to tissue structure and composition. This is crucial to understand mechanisms of meniscal injury, as well as, in regenerative medicine, for the design and development of tissue engineered scaffolds mimicking the native tissue. Hence, the objective of this study was to characterize the dynamic and equilibrium shear properties of human meniscus in relation to its anisotropy and composition. Specimens were prepared from the axial and the circumferential anatomical planes of medial and lateral menisci. Frequency sweeps and stress relaxation tests yielded storage (G') and loss moduli (G″), and equilibrium shear modulus (G). Correlations of moduli with water, glycosaminoglycans (GAGs), and collagen content were investigated. The meniscus exhibited viscoelastic behavior. Dynamic shear properties were related to tissue composition: negative correlations were found between G', G″ and G, and meniscal water content; positive correlations were found for G' and G″ with GAG and collagen (only in circumferential samples). Circumferential samples, with collagen fibers orthogonal to the shear plane, exhibited superior dynamic mechanical properties, with G' ~70 kPa and G″ ~10 kPa, compared to those of the axial plane ~15 kPa and ~1 kPa, respectively. Fiber orientation did not affect the values of G, which ranged from ~50 to ~100 kPa.
Topics: Anisotropy; Collagen; Glycosaminoglycans; Humans; Menisci, Tibial; Meniscus
PubMed: 33730559
DOI: 10.1016/j.jbiomech.2021.110343 -
Scientific Reports Feb 2020Meniscus pathology may promote early osteoarthritis. This study assessed human meniscus functionality (i.e. its response to loading) ex vivo based on quantitative T1,... (Observational Study)
Observational Study
Meniscus pathology may promote early osteoarthritis. This study assessed human meniscus functionality (i.e. its response to loading) ex vivo based on quantitative T1, T1ρ, and T2 mapping as a function of histological degeneration and loading. Forty-five meniscus samples of variable degeneration were harvested from the lateral meniscus body region of 45 patients during total knee arthroplasties. Samples underwent serial mapping on a 3.0-T MRI scanner (Achieva, Philips) using a force-controlled and torque-inducing compressive loading device. Samples were measured at three loading positions, i.e. unloaded, loaded to 2 bar (compression force 37 N) and 4 bar (69 N). Histology (Pauli classification) and biomechanics (Elastic Modulus) served as references. Based on histology, samples were trichotomized as grossly intact (n = 14), mildly degenerative (n = 16), and moderate-to-severely degenerative (n = 15) and analyzed using appropriate parametric and non-parametric tests. For T1, we found loading-induced decreases in all samples, irrespective of degeneration. For T1ρ, zonal increases in intact (apex) and decreases in degenerative samples (base) were found, while for T2, changes were ambiguous. In conclusion, force-controlled loading and serial MR imaging reveal response-to-loading patterns in meniscus. Zonal T1ρ response-to-loading patterns are most promising in differentiating degeneration, while T1 and T2 aren't clearly related to degeneration.and may provide an imaging-based indication of functional tissue properties.
Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Knee; Compressive Strength; Female; Humans; Magnetic Resonance Imaging; Male; Meniscus; Middle Aged; Osteoarthritis
PubMed: 32051526
DOI: 10.1038/s41598-020-59573-4 -
Acta Biomaterialia May 2017To understand how the complex biomechanical functions of the meniscus are endowed by the nanostructure of its extracellular matrix (ECM), we studied the anisotropy and...
UNLABELLED
To understand how the complex biomechanical functions of the meniscus are endowed by the nanostructure of its extracellular matrix (ECM), we studied the anisotropy and heterogeneity in the micromechanical properties of the meniscus ECM. We used atomic force microscopy (AFM) to quantify the time-dependent mechanical properties of juvenile bovine meniscus at deformation length scales corresponding to the diameters of collagen fibrils. At this scale, anisotropy in the elastic modulus of the circumferential fibers, the major ECM structural unit, can be attributed to differences in fibril deformation modes: uncrimping when normal to the fiber axis, and laterally constrained compression when parallel to the fiber axis. Heterogeneity among different structural units is mainly associated with their variations in microscale fiber orientation, while heterogeneity across anatomical zones is due to alterations in collagen fibril diameter and alignment at the nanoscale. Unlike the elastic modulus, the time-dependent properties are more homogeneous and isotropic throughout the ECM. These results enable a detailed understanding of the meniscus structure-mechanics at the nanoscale, and can serve as a benchmark for understanding meniscus biomechanical functions, documenting disease progression and designing tissue repair strategies.
STATEMENT OF SIGNIFICANCE
Meniscal damage is a common cause of joint injury, which can lead to the development of post-traumatic osteoarthritis among young adults. Restoration of meniscus function requires repairing its highly heterogeneous and complex extracellular matrix. Employing AFM, this study quantifies the anisotropic and heterogeneous features of the meniscus ECM structure and mechanics. The micromechanical properties are interpreted within the context of the collagen fibril nanostructure and its variation with tissue anatomical locations. These results provide a fundamental structure-mechanics knowledge benchmark, against which, repair and regeneration strategies can be developed and evaluated with respect to the specialized structural and functional complexity of the native tissue.
Topics: Animals; Anisotropy; Cattle; Extracellular Matrix; Meniscus; Microscopy, Atomic Force
PubMed: 28242455
DOI: 10.1016/j.actbio.2017.02.043 -
International Journal of Molecular... Jul 2021The distribution of differential extracellular matrix (ECM) in the lateral and medial menisci can contribute to knee instability, and changes in the meniscus tissue can...
The distribution of differential extracellular matrix (ECM) in the lateral and medial menisci can contribute to knee instability, and changes in the meniscus tissue can lead to joint disease. Thus, deep proteomic identification of the lateral and medial meniscus cartilage is expected to provide important information for treatment and diagnosis of various knee joint diseases. We investigated the proteomic profiles of 12 lateral/medial meniscus pairs obtained from excess tissue of osteoarthritis patients who underwent knee arthroscopy surgery using mass spectrometry-based techniques and measured 75 ECM protein levels in the lesions using a multiple reaction monitoring (MRM) assay we developed. A total of 906 meniscus proteins with a 1% false discovery rate (FDR) was identified through a tandem mass tag (TMT) analysis showing that the lateral and medial menisci had similar protein expression profiles. A total of 131 ECM-related proteins was included in meniscus tissues such as collagen, fibronectin, and laminin. Our data showed that 14 ECM protein levels were differentially expressed in lateral and medial lesions ( < 0.05). We present the proteomic characterization of meniscal tissue with mass spectrometry-based comparative proteomic analysis and developed an MRM-based assay of ECM proteins correlated with tissue regeneration. The mass spectrometry dataset has been deposited to the MassIVE repository with the dataset identifier MSV000087753.
Topics: Aged; Aged, 80 and over; Extracellular Matrix Proteins; Female; Humans; Male; Meniscus; Osteoarthritis; Proteome
PubMed: 34360947
DOI: 10.3390/ijms22158181 -
Osteoarthritis and Cartilage Apr 2022The human meniscus is essential in maintaining proper knee joint function. The meniscus absorbs shock, distributes loads, and stabilizes the knee joint to prevent the...
OBJECTIVE
The human meniscus is essential in maintaining proper knee joint function. The meniscus absorbs shock, distributes loads, and stabilizes the knee joint to prevent the onset of osteoarthritis. The extent of its shock-absorbing role can be estimated by measuring the energy dissipated by the meniscus during cyclic mechanical loading.
METHODS
Samples were prepared from the central and horn regions of medial and lateral human menisci from 8 donors (both knees for total of 16 samples). Cyclic compression tests at several compression strains and frequencies yielded the energy dissipated per tissue volume. A GEE regression model was used to investigate the effects of compression, meniscal side and region, and water content on energy dissipation in order to account for repeated measures within samples.
RESULTS
Energy dissipation by the meniscus increased with compressive strain from ∼0.1 kJ/m (at 10% strain) to ∼10 kJ/m (at 20% strain) and decreased with loading frequency. Samples from the anterior region provided the largest energy dissipation when compared to central and posterior samples (P < 0.05). Water content for the 16 meniscal tissues was 77.9 (C.I. 72.0-83.8%) of the total tissue mass. A negative correlation was found between energy dissipation and water content (P < 0.05).
CONCLUSION
The extent of energy dissipated by the meniscus is inversely related to loading frequency and meniscal water content.
Topics: Humans; Knee; Knee Joint; Menisci, Tibial; Meniscus; Water
PubMed: 35032627
DOI: 10.1016/j.joca.2022.01.001 -
Chinese Journal of Traumatology =... Jan 2022To retrospectively analyze the clinical outcomes of meniscus repair with simultaneous anterior cruciate ligament (ACL) reconstruction and explore the causes of failure...
PURPOSE
To retrospectively analyze the clinical outcomes of meniscus repair with simultaneous anterior cruciate ligament (ACL) reconstruction and explore the causes of failure of meniscus repair.
METHODS
From May 2013 to July 2018, the clinical data of 165 patients who were treated with meniscus surgery and simultaneous ACL reconstruction, including 69 cases of meniscus repair (repair group) and 96 cases of partial meniscectomy (partial meniscectomy group) were retrospectively analyzed. The exclusion criteria were as follows: (1) ACL rupture associated with fracture, collateral ligament injury, or complex ligament injury; (2) a history of knee surgery; or (3) a significant degree of osteoarthritis. The 69 patients in the repair group were divided into the non-failure group (62 cases) and the failure group (7 cases) depending on the repair effect. Postoperative outcomes of the repair group and the partial meniscectomy group were compared. General conditions and postoperative outcomes of the failure group and the non-failure group were compared. During the median follow-up period of 28 months (range, 4 - 65 months) after the second arthroscopy, postoperative outcomes of seven patients in the failure group were summarized. SPSS 25.0 statistical software was used for statistical analysis. A p value less than 0.05 was considered statistically significant.
RESULTS
Seven patients in the failure group who underwent the second arthroscopy were followed up for (30 ± 17.4) months and their postoperative outcomes were summarized. Compared with the partial meniscectomy group, the International Knee Documentation Committee scores of patients in the repair group improved significantly (p = 0.031). Compared with the non-failure group, more patients in the failure group were younger than 24 years (p = 0.030). The median follow-up period was 39.5 months. All patients recovered well after subsequent partial meniscectomy and relieved clinical symptoms. Visual analog scale scores decreased significantly (p = 0.026), and the International Knee Documentation Committee and Lysholm scores improved significantly (p = 0.046 for both).
CONCLUSION
The failure rate of meniscus repair in this study was 10.1% (7/69), all of which were medial meniscus tears. However, the surgical outcomes of ACL reconstruction were not affected, and there might be a role for graft protection. Therefore, meniscus retears can be successful treated by performing subsequent partial meniscectomy in patients with repair failure.
Topics: Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Humans; Menisci, Tibial; Meniscus; Retrospective Studies
PubMed: 34654594
DOI: 10.1016/j.cjtee.2021.09.005 -
Acta Biomaterialia Jul 2021The meniscus plays a critical role in knee mechanical function but is commonly injured given its central load bearing role. In the adult, meniscus repair is limited,...
The meniscus plays a critical role in knee mechanical function but is commonly injured given its central load bearing role. In the adult, meniscus repair is limited, given the low number of endogenous cells, the density of the matrix, and the limited vascularity. Menisci are fibrocartilaginous tissues composed of a micro-/nano- fibrous extracellular matrix (ECM) and a mixture of chondrocyte-like and fibroblast-like cells. Here, we developed a fibrous scaffold system that consists of bioactive components (decellularized meniscus ECM (dME) within a poly(e-caprolactone) material) fashioned into a biomimetic morphology (via electrospinning) to support and enhance meniscus cell function and matrix production. This work supports that the incorporation of dME into synthetic nanofibers increased hydrophilicity of the scaffold, leading to enhanced meniscus cell spreading, proliferation, and fibrochondrogenic gene expression. This work identifies a new biomimetic scaffold for therapeutic strategies to substitute or replace injured meniscus tissue. STATEMENT OF SIGNIFICANCE: In this study, we show that a scaffold electrospun from a combination of synthetic materials and bovine decellularized meniscus ECM provides appropriate signals and a suitable template for meniscus fibrochondrocyte spreading, proliferation, and secretion of collagen and proteoglycans. Material characterization and in vitro cell studies support that this new bioactive material is susceptible to enzymatic digestion and supports meniscus-like tissue formation.
Topics: Animals; Cattle; Extracellular Matrix; Meniscus; Nanofibers; Tissue Engineering; Tissue Scaffolds
PubMed: 33823327
DOI: 10.1016/j.actbio.2021.03.074 -
Proceedings of the National Academy of... Feb 2020The objective of this study was to examine FoxO expression and FoxO function in meniscus. In menisci from human knee joints with osteoarthritis (OA), FoxO1 and 3...
The objective of this study was to examine FoxO expression and FoxO function in meniscus. In menisci from human knee joints with osteoarthritis (OA), FoxO1 and 3 expression were significantly reduced compared with normal menisci from young and old normal donors. The expression of FoxO1 and 3 was also significantly reduced in mouse menisci during aging and OA induced by surgical meniscus destabilization or mechanical overuse. Deletion of FoxO1 and combined FoxO1, 3, and 4 deletions induced abnormal postnatal meniscus development in mice and these mutant mice spontaneously displayed meniscus pathology at 6 mo. Mice with Col2Cre-mediated deletion of FoxO3 or FoxO4 had normal meniscus development but had more severe aging-related damage. In mature AcanCreERT2 mice, the deletion of FoxO1, 3, and 4 aggravated meniscus lesions in all experimental OA models. FoxO deletion suppressed autophagy and antioxidant defense genes and altered several meniscus-specific genes. Expression of these genes was modulated by adenoviral FoxO1 in cultured human meniscus cells. These results suggest that FoxO1 plays a key role in meniscus development and maturation, and both FoxO1 and 3 support homeostasis and protect against meniscus damage in response to mechanical overuse and during aging and OA.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Disease Models, Animal; Female; Forkhead Box Protein O1; Forkhead Box Protein O3; Humans; Knee Joint; Male; Meniscus; Mice; Mice, Knockout; Middle Aged; Osteoarthritis; Young Adult
PubMed: 31980519
DOI: 10.1073/pnas.1918673117