Effect of meniscus modelling assumptions in a static tibiofemoral finite element model: importance of geometry over material.

Finite element studies of the tibiofemoral joint have increased use in research, with attention often placed on the material models. Few studies assess the effect of meniscus modelling assumptions in image-based models on contact mechanics outcomes. This work aimed to assess the effect of modelling assumptions of the meniscus on knee contact mechanics and meniscus kinematics. A sensitivity analysis was performed using three specimen-specific tibiofemoral models and one generic knee model. The assumptions in representing the meniscus attachment on the tibia (shape of the roots and position of the attachment), the material properties of the meniscus, the shape of the meniscus and the alignment of the joint were evaluated, creating 40 model instances. The values of material parameters for the meniscus and the position of the root attachment had a small influence on the total contact area but not on the meniscus displacement or the force balance between condyles. Using 3D shapes to represent the roots instead of springs had a large influence in meniscus displacement but not in knee contact area. Changes in meniscus shape and in knee alignment had a significantly larger influence on all outcomes of interest, with differences two to six times larger than those due to material properties. The sensitivity study demonstrated the importance of meniscus shape and knee alignment on meniscus kinematics and knee contact mechanics, both being more important than the material properties or the position of the roots. It also showed that differences between knees were large, suggesting that clinical interpretations of modelling studies using single geometries should be avoided.

Removal of GAGs Regulates Mechanical Properties, Collagen Fiber Formation, and Alignment in Tissue Engineered Meniscus.

The complex fibrillar architecture of native meniscus is essential for proper function and difficult to recapitulate in vitro. In the native meniscus, proteoglycan content is low during the development of collagen fibers and progressively increases with aging. In vitro, fibrochondrocytes produce glycosaminoglycans (GAGs) early in culture, in contrast to native tissue, where they are deposited after collagen fibers have formed. This difference in the timing of GAG production hinders the formation of a mature fiber network in such in vitro models. In this study, we removed GAGs from collagen gel-based tissue engineered constructs using chondroitinase ABC (cABC) and evaluated the effect on the formation and alignment of collagen fibers and the subsequent effect on tensile and compressive mechanical properties. Removal of GAGs during maturation of in vitro constructs improved collagen fiber alignment in tissue engineered meniscus constructs. Additionally, removal of GAGs during maturation improved fiber alignment without compromising compressive strength, and this removal improved not only fiber alignment and formation but also tensile properties. The increased fiber organization in cABC-treated groups also appeared to influence the size, shape, and location of defects in these constructs, suggesting that treatment may prevent the propagation of large defects under loading. This data gives another method of modulating the ECM for improved collagen fiber formation and mechanical properties in tissue engineered constructs.

Mechano-bioengineering of the knee meniscus.

The meniscus is a fibrocartilaginous structure of the knee joint that serves a crucial role in joint health and biomechanics. Degeneration or removal of the meniscus is known to lead to a chronic and debilitating disease known as knee osteoarthritis, whose prevalence is expected to increase in the next few decades. Meniscus bioengineering has been developed as a potential alternative to current treatment methods, wherein meniscus-like tissues are engineered using cells, materials, and biomechanical stimuli. The application of mechanical stimulation in meniscus bioengineering has presented varied results but, for the most part, it has been shown to enhance meniscus-like tissue formation. In this review, we summarized literature over the last 10 years of various mechanical stimuli applied in bioengineering meniscus tissues. The role of individual loading types is examined, and the effects on engineered meniscus are evaluated on both molecular and tissue levels. In addition, simulated microgravity is highlighted as a new area of interest in meniscus engineering, and its potential use as a disease-driving platform is discussed. Taken together, with the increased understanding of the effects of mechanical stimulation on bioengineered meniscus tissues, the most suitable loading regime could be developed for meniscus tissue engineering and osteoarthritis modeling.

The MRI-based 3D morphologic changes of knee meniscus under knee weight-bearing and early flexion conditions.

There are few studies investigate morphologic changes of knee meniscus in vivo mechanical loading and three-dimensions (3D) deformation and displacement of the whole meniscus between in vivo mechanical loading and unloading conditions are still unclear. To investigate the displacements and 3D morphological changes of the menisci under knee weight-bearing and early flexion conditions in healthy adults using a Magnetic Resonance Imaging (MRI)-compatible loading device (a 3.0 T MR imaging system) combined with a newly developed 3D comparison technique. Fifteen healthy volunteers were recruited in this cross-sectional observational study. Each subject underwent MRIs of their dominant right knee in eight different scanning conditions using a 3.0-T MRI scanner with a custom-made MRI-compatible loading device. The knee meniscus images were 3D reconstructed, and dimensional comparisons were made for each meniscal model with baseline (0°-unloaded model). The morphologic changes of the meniscal-anterior horn (AH), body (BD), and posterior horn (PH) regions were expressed as mean positive and negative deviations. The displacements were further investigated, and the meniscal extrusions of different subregions were measured. The morphologic changing patterns of human meniscus under loading and flexions were presented using 3D chromatic maps. The bilateral menisci were generally shifting laterally and posteriorly in most flexion angles and were changing medially and anteriorly under fully extended knee loading conditions. The mean deviations were more significant with loading at 0° of knee flexion, while the PH region in the lateral side changed further posteriorly with loading in 30° flexion. Most of the differences were not significant in other flexion angles between loading conditions. The extrusion of meniscus's medial body was greater in full extension compared to any other flexing angles. Mechanical loading can significantly deform the menisci in knee extension; however, this effect is limited during knee flexion. Current study can be used as a reference for the evaluations of the integrity in meniscal functions.

Quantifying the differential functional behavior between the medial and lateral meniscus after posterior meniscus root tears.

Meniscus tears of the knee are among the most common orthopedic knee injury. Specifically, tears of the posterior root can result in abnormal meniscal extrusion leading to decreased function and progressive osteoarthritis. Despite contemporary surgical treatments of posterior meniscus root tears, there is a low rate of healing and an incidence of residual meniscus extrusion approaching 30%, illustrating an inability to recapitulate native meniscus function. Here, we characterized the differential functional behavior of the medial and lateral meniscus during axial compression load and dynamic knee motion using a cadaveric model. We hypothesized essential differences in extrusion between the medial and lateral meniscus in response to axial compression and knee range of motion. We found no differences in the amount of meniscus extrusion between the medial and lateral meniscus with a competent posterior root (0.338mm vs. 0.235mm; p-value = 0.181). However, posterior root detachment resulted in a consistently increased meniscus extrusion for the medial meniscus compared to the lateral meniscus (2.233mm vs. 0.4705mm; p-value < 0.0001). Moreover, detachment of the posterior root of the medial meniscus resulted in an increase in extrusion at all angles of knee flexion and was most pronounced (4.00mm ± 1.26mm) at 30-degrees of knee flexion. In contrast, the maximum mean extrusion of the lateral meniscus was 1.65mm ± 0.97mm, occurring in full extension. Furthermore, only the medial meniscus extruded during dynamic knee flexion after posterior root detachment. Given the differential functional behaviors between the medial and lateral meniscus, these findings suggest that posterior root repair requires reducing overall meniscus extrusion and recapitulating the native functional responses specific to each meniscus.

The regenerative effect of different growth factors and platelet lysate on meniscus cells and mesenchymal stromal cells and proof of concept with a functionalized meniscus implant.

Meniscus regeneration could be enhanced by targeting meniscus cells and mesenchymal stromal cells (MSCs) with the right growth factors. Combining these growth factors with the Collagen Meniscus Implant (CMI®) could accelerate cell ingrowth and tissue formation in the implant and thereby improve clinical outcomes. Using a transwell migration assay and a micro-wound assay, the effect of insulin-like growth factor-1, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF-ß1), fibroblast growth factor, and platelet lysate (PL) on migration and proliferation of meniscus cells and MSCs was assessed. The formation of extracellular matrix under influence of the above-mentioned growth factors was assessed after 28 days of culture of both MSCs and meniscus cells. As a proof of concept, the CMI® was functionalized with a VEGF binding peptide and coated with platelet-rich plasma (PRP) for clinical application. Our results demonstrate that PDGF, TGF-ß1, and PL stimulate migration, proliferation, and/or extracellular matrix production of meniscus cells and MSCs. Additionally, the CMI® was successfully functionalized with a VEGF binding peptide and PRP which increased migration of meniscus cell and MSC into the implant. This study demonstrates proof of concept of functionalizing the CMI® with growth factor binding peptides. A CMI® functionalized with the right growth factors holds great potential for meniscus replacement after partial meniscectomy.

Measuring the Internal Stress in Ovine Meniscus During Simulated In Vivo Gait Kinematics: A Novel Method Using Fibre Optic Technology.

Changes in stress transferred across articular joints have been described as a substantial factor in the initiation and progression of joint disease such as post-traumatic osteoarthritis and have thus been of interest to biomechanical researchers. However, to date, stress magnitudes within the menisci have not been successfully measured. In this study, a novel method for measuring stress within the menisci is presented. Small Fibre Bragg Grating (FBG) sensors were inserted inside menisci and used to measure mechanical stress during replicated gait cycles. In-vitro stress measurements within the menisci were preformed for healthy gait and gait following surgical damage to the joints. Together with our capability to reproduce in vivo motions accurately, the improvements in fibre optic technology have allowed for the first direct measurement of mechanical stress in menisci.

Characterization of regional meniscal cell and chondrocyte phenotypes and chondrogenic differentiation with histological analysis in osteoarthritic donor-matched tissues.

Meniscus degeneration is closely related to the progression of knee osteoarthritis (OA). However, there is currently a lack of quantitative and objective metrics to assess OA meniscal cell phenotypes. In this study we investigated the phenotypic markers and chondrogenic potency of avascular and vascular meniscal cells and chondrocytes from medial OA knee joints (n = 10). Flow cytometry results showed that a significantly greater percentage of meniscal cells were positive for CD49b, CD49c and CD166 compared to donor-matched chondrocytes after 14 days in monolayer culture. The integrins, CD49b and CD29, were expressed at a significantly higher level on avascular meniscal cells derived from tissues with a more degenerated inner border than non-degenerate menisci, suggesting that the integrin family may play an important role in meniscus OA pathology. Collagen fibres arranged in a "tree-like" formation within the meniscus appeared to have less blood vessels associated with them in the vascular region of the most degenerate menisci, which may indicate that such structures are involved in the pathological process. We have demonstrated that meniscal cells derived from the lateral meniscus in medial OA patients have chondrogenic capacity in vitro and hence could represent a potential cell source to consider for meniscus tissue engineering.

Proteoglycans exert a significant effect on human meniscal stiffness through ionic effects.

BACKGROUND: Proteoglycans contribute to mechanical stiffness in articular cartilage, aiding load transmission. The magnitude of the ionic contribution of proteoglycans to the stiffness of human meniscal tissue has not been established. METHODS: Thirty-six discs of human meniscal tissue were placed within a custom confined compression chamber and bathed in three solutions of increasing ionic concentration. Following a 0.3 N preload, at equilibrium, a 10% ramp compressive strain was followed by a 7200 s hold phase. A nonlinear poroviscoelastic model with strain dependent permeability was fitted to resultant stress relaxation curves. All samples were assayed for proteoglycan content. Model parameters were analysed using multivariate analysis of variance whilst proteoglycan content was compared using a univariate analysis of variance model. FINDINGS: A significant difference (p < .05) was observed in the value of the Young's modulus (E) between samples tested in deionised water compared to those tested in solutions of high ionic concentration. No differences were observed in the zero-strain permeability or the exponential strain dependent stiffening coefficient. Proteoglycan content was not found to differ with solution; but was found to be significantly increased in the middle meniscal region of both menisci. INTERPRETATION: Proteoglycans make a significant ionic contribution to mechanical stiffness of the meniscus, increasing it by 58% in the physiological condition. It is therefore critical that meniscal regeneration strategies attempt to recreate the function of proteoglycans to ensure normal meniscal function.

EMG-Assisted Muscle Force Driven Finite Element Model of the Knee Joint with Fibril-Reinforced Poroelastic Cartilages and Menisci.

Abnormal mechanical loading is essential in the onset and progression of knee osteoarthritis. Combined musculoskeletal (MS) and finite element (FE) modeling is a typical method to estimate load distribution and tissue responses in the knee joint. However, earlier combined models mostly utilize static-optimization based MS models and muscle force driven FE models typically use elastic materials for soft tissues or analyze specific time points of gait. Therefore, here we develop an electromyography-assisted muscle force driven FE model with fibril-reinforced poro(visco)elastic cartilages and menisci to analyze knee joint loading during the stance phase of gait. Moreover, since ligament pre-strains are one of the important uncertainties in joint modeling, we conducted a sensitivity analysis on the pre-strains of anterior and posterior cruciate ligaments (ACL and PCL) as well as medial and lateral collateral ligaments (MCL and LCL). The model produced kinematics and kinetics consistent with previous experimental data. Joint contact forces and contact areas were highly sensitive to ACL and PCL pre-strains, while those changed less cartilage stresses, fibril strains, and fluid pressures. The presented workflow could be used in a wide range of applications related to the aetiology of cartilage degeneration, optimization of rehabilitation exercises, and simulation of knee surgeries.

Meniscus Matrix Remodeling in Response to Compressive Forces in Dogs.

Joint motion and postnatal stress of weight bearing are the principal factors that determine the phenotypical and architectural changes that characterize the maturation process of the meniscus. In this study, the effect of compressive forces on the meniscus will be evaluated in a litter of 12 Dobermann Pinschers, of approximately 2 months of age, euthanized as affected by the quadriceps contracture muscle syndrome of a single limb focusing on extracellular matrix remodeling and cell-extracellular matrix interaction (i.e., meniscal cells maturation, collagen fibers typology and arrangement). The affected limbs were considered as models of continuous compression while the physiologic loaded limbs were considered as controls. The results of this study suggest that a compressive continuous force, applied to the native meniscal cells, triggers an early maturation of the cellular phenotype, at the expense of the proper organization of collagen fibers. Nevertheless, an application of a compressive force could be useful in the engineering process of meniscal tissue in order to induce a faster achievement of the mature cellular phenotype and, consequently, the earlier production of the fundamental extracellular matrix (ECM), in order to improve cellular viability and adhesion of the cells within a hypothetical synthetic scaffold.

Bioactive proteins delivery through core-shell nanofibers for meniscal tissue regeneration.

Mimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can help engineer tissue with the potential to grow, mature, and regenerate after in vivo implantation. We electrospun nanofibers encapsulating platelet-derived growth factor (PDGF-BB), which is a potent mitogen and chemoattractant in a core of serum albumin contained within a shell of polylactic acid. We controlled the local PDGF-BB release by adding water-soluble polyethylene glycol to the polylactic acid shell to serve as a porogen. The novel core-shell nanofibers generated 3D scaffolds with an interconnected macroporous structure, with appropriate mechanical properties and with high cell compatibility. Incorporating PDGF-BB increased cell viability, proliferation, and infiltration, and upregulated key genes involved in meniscal extracellular matrix synthesis in human meniscal and synovial cells. Our results support proof of concept that these core-shell nanofibers can create a cell-favorable nanoenvironment and can serve as a system for sustained release of bioactive factors.

A multi-purpose force-controlled loading device for cartilage and meniscus functionality assessment using advanced MRI techniques.

Response to loading of soft tissues as assessed by advanced magnetic resonance imaging (MRI) techniques is a promising approach to evaluate tissue functionality beyond (statically obtained) structural and compositional features. As cartilage and meniscus pathologies are closely intertwined in osteoarthritis (OA) and beyond, both tissues should ideally be studied to elucidate further the underlying mechanisms involved in load transmission and its failure leading to OA. Hence, we devised, constructed and validated a dedicated MRI-compatible pneumatic force-controlled loading device to study cartilage and meniscus functionality in a standardized and reproducible manner and in reference to alternative tissue evaluation methods. Mechanical reference measurements using digital force sensors confirmed the reproducible application of forces in the range of 0-76N. To demonstrate the device's utility in a basic research context, MRI measurements of human articular cartilage (obtained from the lateral femoral condyle, n = 5) and meniscus (obtained from lateral meniscus body, n = 5) were performed in the unloaded (δ0) and loaded configurations (δ1: [cartilage] 0.75 bar corresponding to 15.1 N, [meniscus] 2 bar corresponding to 37.1 N; δ2: [cartilage] 1.5 bar corresponding to 28.6 N, [meniscus] 4 bar corresponding to 69.1 N). Cartilage samples were directly indented, while meniscus samples were subject to torque-induced compression using a dedicated lever compression device. Morphological MR Imaging using Proton Density-weighted sequences and quantitative MR Imaging using T2 and T1ρ mapping were performed serially and at high resolution. For reference, samples underwent subsequent biomechanical and histological reference evaluation. In conclusion, the force-controlled loading device has been validated for the non-invasive response-to-loading assessment of human cartilage and meniscus samples by advanced MRI techniques. Hereby, both tissues may be functionally evaluated in combination, beyond mere static analysis and in reference to histological and biomechanical measures.

Type III collagen is a key regulator of the collagen fibrillar structure and biomechanics of articular cartilage and meniscus.

Despite the fact that type III collagen is the second most abundant collagen type in the body, its contribution to the physiologic maintenance and repair of skeletal tissues remains poorly understood. This study queried the role of type III collagen in the structure and biomechanical functions of two structurally distinctive tissues in the knee joint, type II collagen-rich articular cartilage and type I collagen-dominated meniscus. Integrating outcomes from atomic force microscopy-based nanomechanical tests, collagen fibril nanostructural analysis, collagen cross-link analysis and histology, we elucidated the impact of type III collagen haplodeficiency on the morphology, nanostructure and biomechanical properties of articular cartilage and meniscus in Col3a1+/- mice. Reduction of type III collagen leads to increased heterogeneity and mean thickness of collagen fibril diameter, as well as reduced modulus in both tissues, and these effects became more pronounced with skeletal maturation. These data suggest a crucial role of type III collagen in mediating fibril assembly and biomechanical functions of both articular cartilage and meniscus during post-natal growth. In articular cartilage, type III collagen has a marked contribution to the micromechanics of the pericellular matrix, indicating a potential role in mediating the early stage of type II collagen fibrillogenesis and chondrocyte mechanotransduction. In both tissues, reduction of type III collagen leads to decrease in tissue modulus despite the increase in collagen cross-linking. This suggests that the disruption of matrix structure due to type III collagen deficiency outweighs the stiffening of collagen fibrils by increased cross-linking, leading to a net negative impact on tissue modulus. Collectively, this study is the first to highlight the crucial structural role of type III collagen in both articular cartilage and meniscus extracellular matrices. We expect these results to expand our understanding of type III collagen across various tissue types, and to uncover critical molecular components of the microniche for regenerative strategies targeting articular cartilage and meniscus repair.

PCL-MECM-Based Hydrogel Hybrid Scaffolds and Meniscal Fibrochondrocytes Promote Whole Meniscus Regeneration in a Rabbit Meniscectomy Model.

Regeneration of an injured meniscus continues to be a scientific challenge due to its poor self-healing potential. Tissue engineering provides an avenue for regenerating a severely damaged meniscus. In this study, we first investigated the superiority of five concentrations (0%, 0.5%, 1%, 2%, and 4%) of meniscus extracellular matrix (MECM)-based hydrogel in promoting cell proliferation and the matrix-forming phenotype of meniscal fibrochondrocytes (MFCs). We found that the 2% group strongly enhanced chondrogenic marker mRNA expression and cell proliferation compared to the other groups. Moreover, the 2% group showed the highest glycosaminoglycan (GAG) and collagen production by day 14. We then constructed a hybrid scaffold by 3D printing a wedge-shaped poly(ε-caprolactone) (PCL) scaffold as a backbone, followed by injection with the optimized MECM-based hydrogel (2%), which served as a cell delivery system. The hybrid scaffold (PCL-hydrogel) clearly yielded favorable biomechanical properties close to those of the native meniscus. Finally, PCL scaffold, PCL-hydrogel, and MFCs-loaded hybrid scaffold (PCL-hydrogel-MFCs) were implanted into the knee joints of New Zealand rabbits that underwent total medial meniscectomy. Six months postimplantation we found that the PCL-hydrogel-MFCs group exhibited markedly better gross appearance and cartilage protection than the PCL scaffold and PCL-hydrogel groups. Moreover, the regenerated menisci in the PCL-hydrogel-MFCs group had similar histological structures, biochemical contents, and biomechanical properties as the native menisci in the sham operation group. In conclusion, PCL-MECM-based hydrogel hybrid scaffold seeded with MFCs can successfully promote whole meniscus regeneration, and cell-loaded PCL-MECM-based hydrogel hybrid scaffold may be a promising strategy for meniscus regeneration in the future.

Regulation of proteoglycan production by varying glucose concentrations controls fiber formation in tissue engineered menisci.

Fibrillar collagens are highly prevalent in the extracellular matrix of all connective tissues and therefore commonly used as a biomaterial in tissue engineering applications. In the native environment, collagen fibers are arranged in a complex hierarchical structure that is often difficult to recreate in a tissue engineered construct. Small leucine rich proteoglycans as well as hyaluronan binding proteoglycans, aggrecan and versican, have been implicated in regulating fiber formation. In this study, we modified proteoglycan production in vitro by altering culture medium glucose concentrations (4500, 1000, 500, 250, and 125 mg/L), and evaluated its effect on the formation of collagen fibers inside tissue engineered meniscal constructs. Reduction of extracellular glucose resulted in a dose dependent decrease in total sulfated glycosaminoglycan (GAG) production, but minimal decreases of decorin and biglycan. However, fibromodulin doubled in production between 125 and 4500 mg/L glucose concentration. A peak in fiber formation was observed at 500 mg/L glucose concentration and corresponded with reductions in total GAG production. Fiber formation reduction at 125 and 250 mg/L glucose concentrations are likely due to changes in metabolic activity associated with a limited supply of glucose. These results point to proteoglycan production as a means to manipulate fiber architecture in tissue engineered constructs. STATEMENT OF SIGNIFICANCE: Fibrillar collagens are highly prevalent in the extracellular matrix of all connective tissues; however achieving appropriate assembly and organization of collagen fibers in engineered connective tissues is a persistent challenge. Proteoglycans have been implicated in regulating collagen fiber organization both in vivo and in vitro, however little is known about methods to control proteoglycan production and the subsequent fiber organization in tissue engineered menisci. Here, we show that media glucose content can be optimized to control proteoglycan production and collagen fiber assembly, with optimal collagen fiber assembly occurring at sub-physiologic levels of glucose.

Platelet-rich gel-incorporated silk scaffold promotes meniscus regeneration in a rabbit total meniscectomy model.

Aim: To investigate whether platelet-rich gel (PRG) incorporation could promote meniscal regeneration of the silk scaffold. Materials & methods: A PRG-incorporated silk sponge was fabricated for reconstruction of the meniscus in a rabbit meniscectomy model. Subsequently, characterization of the scaffold, as well as the in vitro cytocompatibility and in vivo function was evaluated. Results: Our results showed that the PRG-incorporated silk scaffold provided a sustained release of TGF-ß1 over 1 week. The PRG enhanced the cytocompatibility in vitro and cell infiltration in vivo of the silk sponge. Meanwhile, the implantation of the composite in situ ameliorated the cartilage degeneration in knee at 3 months. Conclusion: These findings indicated that PRG-incorporated silk scaffold could promote functional regeneration of the meniscus and effectively prevented subsequent osteoarthritis after meniscectomy.

Meniscus regeneration combining meniscus and mesenchymal stromal cells in a degradable meniscus implant: an in vitro study.

Meniscus regeneration is an unmet clinical need as damage to the meniscus is common and causes early osteoarthritis. The aim of the present study was to investigate the feasibility of a one-stage cell-based treatment for meniscus regeneration by augmenting a resorbable collagen-based implant with a combination of recycled meniscus cells and mesenchymal stromal cells (MSCs). Cell communication and fate of the different cell types over time in co-culture were evaluated by connexin 43 staining for gap junctions and polymerase chain reaction (PCR) to discriminate between meniscus cells and MSCs, based on a Y-chromosome gene. To define optimal ratios, human meniscus cells and bone-marrow-derived MSCs were cultured in different ratios in cell pellets and type I collagen hydrogels. In addition, cells were seeded on the implant in fibrin glue by static seeding or injection. Cellular communication by gap junctions was shown in co-culture and a decrease in the amount of MSCs over time was demonstrated by PCR. 20 : 80 and 10 : 90 ratios showed significantly highest glycosaminoglycan and collagen content in collagen hydrogels. The same statistical trend was found in pellet cultures. Significantly more cells were present in the injected implant and cell distribution was more homogenous as compared to the statically seeded implant. The study demonstrated the feasibility of a new one-stage cell-based procedure for meniscus regeneration, using 20 % meniscus cells and 80 % MSCs seeded statically on the implant. In addition, the stimulatory effect of MSCs towards meniscus cells was demonstrated by communication through gap junctions.

Anterior and Rotational Knee Laxity Does Not Affect Patient-Reported Knee Function 2 Years After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: While a primary goal of anterior cruciate ligament (ACL) reconstruction is to reduce pathologically increased anterior and rotational knee laxity, the relationship between knee laxity after ACL reconstruction and patient-reported knee function remains unclear. HYPOTHESIS: There would be no significant correlation between the degree of residual anterior and rotational knee laxity and patient-reported outcomes (PROs) 2 years after primary ACL reconstruction. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: From a prospective multicenter nested cohort of patients, 433 patients younger than 36 years of age injured in sports with no history of concomitant ligament surgery, revision ACL surgery, or surgery of the contralateral knee were identified and evaluated at a minimum 2 years after primary ACL reconstruction. Each patient underwent Lachman and pivot-shift evaluation as well as a KT-1000 arthrometer assessment along with Knee injury and Osteoarthritis Outcome Score and subjective International Knee Documentation Committee (IKDC) scores. A proportional odds logistic regression model was used to predict each 2-year PRO score, controlling for preoperative score, age, sex, body mass index, smoking, Marx activity score, education, subsequent surgery, meniscal and cartilage status, graft type, and range of motion asymmetry. Measures of knee laxity were independently added to each model to determine correlation with PROs. RESULTS: Side-to-side manual Lachman differences were IKDC A in 246 (57%) patients, IKDC B in 183 (42%) patients, and IKDC C in 4 (<1%) patients. Pivot-shift was classified as IKDC A in 209 (48%) patients, IKDC B in 183 (42%) patients, and IKDC C in 11 (2.5%) patients. The mean side-to-side KT-1000 difference was 2.0 ± 2.6 mm. No significant correlations were noted between pivot-shift or anterior tibial translation as assessed by Lachman or KT-1000 and any PRO. All predicted differences in PROs based on IKDC A versus B pivot-shift and anterior tibial translation were less than 4 points. CONCLUSION: Neither the presence of IKDC A versus B pivot-shift nor increased anterior tibial translation of up to 6 mm is associated with clinically relevant decreases in PROs 2 years after ACL reconstruction.

Understanding the Stiff-to-Compliant Transition of the Meniscal Attachments by Spatial Correlation of Composition, Structure, and Mechanics.

Recently, the scientific community has shown considerable interest in engineering tissues with organized compositional and structural gradients to mimic hard-to-soft tissue interfaces. This effort is hindered by an incomplete understanding of the construction of native tissue interfaces. In this work, we combined Raman microscopy and confocal elastography to map compositional, structural, and mechanical features across the stiff-to-compliant interface of the attachments of the meniscus in the knee. This study provides new insight into the methods by which biology mediates multiple orders of magnitude changes in stiffness over tens of microns. We identified how the nano- to mesoscale architecture mediates complex microscale transitional regions across the interface: two regions defined by chemical composition, five distinguished by structural features, and three mechanically distinct regions. We identified three major components that lead to a robust interface between a soft tissue and bone: mobile collagen fiber units, a continuous interfacial region, and a local stiffness gradient. This tissue architecture allows for large displacements of collagen fibers in the attachments, enabling meniscal movement without localizing strains to the soft tissue-to-bone interface. The interplay of these regions reveals a method relying on hierarchical structuring across multiple length scales to minimize stress concentrators between highly dissimilar materials. These insights inspire new design strategies for synthetic soft tissue-to-bone attachments and biomimetic material interfaces.