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Background: The menisci are integral to normal knee function. The purpose of this study was to measure the contact pressures transmitted to the medial tibial plateau under physiological loads as a function of the percentage of the meniscus involved by the radial tear or repair. Our hypotheses were that (1) there is a threshold size of radial tears above which contact mechanics are adversely affected, and (2) partial meniscectomy results in increased contact pressure compared with that found after meniscal repair., Methods: A knee simulator was used to apply physiological multidirectional dynamic gait loads across human cadaver knees. A sensor inserted below the medial meniscus recorded contact pressures in association with (1) an intact meniscus, (2) a radial tear involving 30% of the meniscal rim width, (3) a radial tear involving 60% of the width, (4) a radial tear involving 90% of the width, (5) an inside-out repair with horizontal mattress sutures, and (6) a partial meniscectomy. The effects of these different types of meniscal manipulation on the magnitude and location of the peak contact pressure were assessed at 14% and 45% of the gait cycle., Results: The peak tibial contact pressure in the intact knees was 6 +/- 0.5 MPa and 7.4 +/- 0.6 MPa at 14% and 45% of the gait cycle, respectively. The magnitude and location of the peak contact pressure were not affected by radial tears involving up to 60% of the meniscal rim width. Radial tears involving 90% resulted in a posterocentral shift in peak-pressure location manifested by an increase in pressure in that quadrant of 1.3 +/- 0.5 MPa at 14% of the gait cycle relative to the intact condition. Inside-out mattress suture repair of a 90% tear did not restore the location of the pressure peak to that of the intact knee. Partial meniscectomy led to a further increase in contact pressure in the posterocentral quadrant of 1.4 +/- 0.7 MPa at 14% of the gait cycle., Conclusions: Large radial tears of the medial meniscus are not functionally equivalent to meniscectomies; the residual meniscus continues to provide some load transmission and distribution functions across the joint.

The menisci of the knee play an important role in joint function and our understanding of knee mechanics and tissue interactions can be enhanced through computational models of the tibio-menisco-femoral structure. Several finite element models of the knee that include meniscus-cartilage contact exist, but these models are typically limited to simplified boundary conditions. Movement simulation and musculoskeletal modeling can predict muscle forces, but are typically performed using the multibody method with simplified representation of joint structures. This study develops a subject specific computational model of the knee with menisci that can be incorporated into neuromusculoskeletal models within a multibody framework. Meniscus geometries from a 78-year-old female right cadaver knee were divided into 61 discrete elements (29 medial and 32 lateral) that were connected through 6x6 stiffness matrices. An optimization and design of experiments approach was used to determine parameters for the 6x6 stiffness matrices such that the force-displacement relationship of the meniscus matched that of a linearly elastic transversely isotropic finite element model for the same cadaver knee. Similarly, parameters for compliant contact models of tibio-menisco-femoral articulations were derived from finite element solutions. As a final step, a multibody knee model was developed and placed within a dynamic knee simulator model and the tibio-femoral and patello-femoral kinematics compared to an identically loaded cadaver knee. RMS errors between finite element displacement and multibody displacement after parameter optimization were 0.017 mm for the lateral meniscus and 0.051 mm for the medial meniscus. RMS errors between model predicted and experimental cadaver kinematics during a walk cycle were less than 11 mm translation and less than 7 degrees orientation. A small improvement in kinematics, compared to experimental measurements, was seen when the menisci were included versus a model without the menisci. With the menisci the predicted tibio-femoral contact force was significantly reduced on the lateral side (937 N peak force versus 633 N peak force), but no significant reduction was seen on the medial side., (Copyright 2010 IPEM. Published by Elsevier Ltd. All rights reserved.)

Objective: Meniscal tears are a common knee injury and increased levels of interleukin-1 (IL-1) have been measured in injured and degenerated joints. Studies have shown that IL-1 decreases the shear strength, cell accumulation, and tissue formation in meniscal repair interfaces. While mechanical stress and IL-1 modulate meniscal biosynthesis and degradation, the effects of dynamic loading on meniscal repair are unknown. The purpose of this study was to determine the effects of mechanical compression on meniscal repair under normal and inflammatory conditions., Experimental Design: Explants were harvested from porcine medial menisci. To simulate a full-thickness defect, a central core was removed and reinserted. Explants were loaded for 4h/day at 1 Hz and 0%-26% strain for 14 days in the presence of 0 or 100 pg/mL of IL-1. Media were assessed for matrix metalloproteinase (MMP) activity, aggrecanase activity, sulfated glycosaminoglycan (S-GAG) release, and nitric oxide (NO) production. After 14 days, biomechanical testing and histological analyses were performed., Results: IL-1 increased MMP activity, S-GAG release, and NO production, while decreasing the shear strength and tissue repair in the interface. Dynamic loading antagonized IL-1-mediated inhibition of repair at all strain amplitudes. Neither IL-1 treatment nor strain altered aggrecanase activity. Additionally, strain alone did not alter meniscal healing, except at the highest strain magnitude (26%), a level that enhanced the strength of repair., Conclusions: Dynamic loading blocked the catabolic effects of IL-1 on meniscal repair, suggesting that joint loading through physical therapy may be beneficial in promoting healing of meniscal lesions under inflammatory conditions., (Copyright 2010 Osteoarthritis Research Society International. All rights reserved.)

Cartilage is a tissue with only limited reparative capacities. A small part of its volume is composed of cells, the remaining part being the hydrated extracellular matrix (ECM) with collagens and proteoglycans as its main constituents. The functioning of cartilage depends heavily on its ECM. Although it is known that the various (fibro)cartilaginous tissues (articular cartilage, annulus fibrosus, nucleus pulposus, and meniscus) differ from one each other with respect to their molecular make-up, remarkable little quantitative information is available with respect to its biochemical constituents, such as collagen content, or the various posttranslational modifications of collagen. Furthermore, we have noticed that tissue-engineering strategies to replace cartilaginous tissues pay in general little attention to the biochemical differences of the tissues or the phenotypical differences of the (fibro)chondrocytes under consideration. The goal of this paper is therefore to provide quantitative biochemical data from these tissues as a reference for further studies. We have chosen the goat as the source of these tissues, as this animal is widely accepted as an animal model in orthopaedic studies, e.g. in the field of cartilage degeneration and tissue engineering. Furthermore, we provide data on mRNA levels (from genes encoding proteins/enzymes involved in the synthesis and degradation of the ECM) from (fibro)chondrocytes that are freshly isolated from these tissues and from the same (fibro)chondrocytes that are cultured for 18 days in alginate beads. Expression levels of genes involved in the cross-linking of collagen were different between cells isolated from various cartilaginous tissues. This opens the possibility to include more markers than the commonly used chondrogenic markers type II collagen and aggrecan for cartilage tissue-engineering applications., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background: Concerning meniscal tissue regeneration, many investigators have studied the development of a tissue-engineered meniscus. However, the utility still remains unknown., Hypothesis: Implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect may significantly enhance fibrocartilage regeneration in vivo in the defect., Study Design: Controlled laboratory study., Methods: Seventy-five mature rabbits were used in this study. In each animal, an anterior one-third of the right medial meniscus was resected. Then, the animals were divided into the following 3 groups of 25 rabbits each: In group 1, no treatment was applied to the meniscal defect. In group 2, the defect was covered with a fascia sheath. In group 3, after the resected meniscus was fragmented into small pieces, the fragments were grafted into the defect. Then, the defect with the meniscal fragments was covered with a fascia sheath. In each group, 5 rabbits were used for histological evaluation at 3, 6, and 12 weeks after surgery, and 5 rabbits were used for biomechanical evaluation at 6 and 12 weeks after surgery., Results: Histologically, large round cells in group 3 were scattered in the core portion of the meniscus-shaped tissue, and the matrix around these cells was positively stained by safranin O and toluisin blue at 12 weeks. The histological score of group 3 was significantly higher than that of group 1 and group 2. Biomechanically, the maximal load and stiffness of group 3 were significantly greater than those of groups 1 and 2., Conclusion: This study clearly demonstrated that implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect significantly enhanced fibrocartilage regeneration in vivo in the defect at 12 weeks after implantation in the rabbit., Clinical Relevance: This study proposed a novel strategy to treat a large defect after a meniscectomy.

The susceptibility of meniscus allografts to enzymatic degradation may be reduced through tissue stabilization. We have previously reported on an epoxide-based crosslinker, triglycidyl amine (TGA), which can be used alone or with a bisphosphonate (MABP) to stabilize heterograft heart valves and reduce their pathologic calcification. Our objective was to evaluate the effects of TGA and TGA-MABP pretreatment on an orthopedic allograft involving meniscus crosslinking, degradation, calcification, and compressive properties. Ovine menisci treated with TGA or TGA-MABP for up to seven days and glutaraldehyde crosslinked controls were examined in vitro for degree of crosslinking, resistance to degradation by collagenase, and material property changes. Likewise treated menisci were implanted in rats for eight weeks and examined for calcium content and biomechanical changes. TGA treatment for three days significantly reduced collagen loss by 88% and increased thermal denaturation temperatures (Ts) above 80 degrees C versus Ts of 70 degrees C or less for non-crosslinked meniscus. In vitro, TGA and TGA-MABP significantly increased aggregate modulus by 19% and 32% compared to native controls, respectively. TGA decreased permeability by 53% while TGA-MABP increased it by 303%. In vivo, TGA significantly reduced explant calcification by 42% compared to glutaraldehyde, and including MABP reduced it by 90%. Analyses revealed that TGA and TGA-MABP stabilized menisci had significantly lower modulus and permeability values than glutaraldehyde controls by at least 28% and 86%, respectively. It is concluded that TGA crosslinking of meniscus increases resistance to both collagenase degradation and pathologic calcification, while demonstrating comparable or improved biomechanical properties versus glutaraldehyde controls.

Purpose: The purpose of this biomechanical study was to investigate the potential effect of a nonanatomic repair of the meniscal horn attachment on the resultant circumferential tension in a large animal model and to show that the circumferential tension of the meniscus affects the local stress of the cartilage., Methods: All investigations were done in the medial compartment of porcine knees. First, the anterior horn attachment of the meniscus was mechanically separated from the surrounding tibial bone and fitted with a force transducer (n = 8). The femorotibial joint was loaded in compression at different flexion angles, and the resultant tension at the horn attachment was recorded. The measurements were done with the horn attachment at its anatomic position and repeated with the horn attachment being displaced medially or laterally by 3 mm. In the second part the local deformation of the cartilage under a femorotibial compressive load was measured at different levels of meniscal hoop tension (n = 5)., Results: A nonanatomic position of the horn attachment had a significant effect on the resultant tension (P < .01). Placing the horn attachment 3 mm medially decreased the tension at the horn attachment by 49% to 73%, depending on flexion angle and femorotibial load. The opposite placement resulted in a relative increase in the tension by 28% to 68%. Lower levels of meniscal hoop tension caused increased deformation of the cartilage (P < .05), indicating increased local stress., Conclusions: A nonanatomic position of the horn attachment strongly affects conversion of femorotibial loads into circumferential tension. There is a narrow window for a functionally sufficient repair of meniscal root tears., Clinical Relevance: Although clinical inferences are limited because the specimens used were from a different species, there seems to be only a narrow window for a mechanically sufficient repair of root tears., (Copyright 2010 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Meniscectomies have been shown to lead to osteoarthritis and the success of meniscal replacements remains questionable. It has been suggested that the success of a meniscal replacement is dependent on several factors, one of which is the secure fixation and firm attachment of the replacement to the tibial plateau at the horn locations. To aid in the development of meniscal replacements, the objectives of the current study were to determine the time-dependent and failure properties of human meniscal attachments. In contrast to the time-dependent tests, during uniaxial failure testing a charge-coupled video camera was used to document the local strain and linear modulus distribution across the surface of the attachments. The lateral attachments were statistically smaller in cross-sectional area and longer than the medial attachments. The anterior attachments were statistically longer and had a smaller cross-sectional area than the posterior attachments. From the stress relaxation tests, the load and stress relaxation rates of the medial anterior attachment were statistically greater than the medial posterior attachment. There were no significant differences in the creep, structural properties or the ultimate stress between the different attachments. Ultimate strain varied between attachments, as well as along the length of the attachment. Ultimate strain in the meniscus region (10.4+/-6.9%) and mid-substance region (12.7+/-16.4%) was smaller than the bony insertion region (32.2+/-21.5%). The lateral and anterior attachments were also found to have statistically greater strain than the medial and posterior attachments, respectively. The linear modulus was statistically weaker in the bony insertion region (69.7+/-33.7MPa) compared to the meniscus region (153+/-123MPa) and mid-substance region (195+/-121MPa). Overall the anterior attachments (169+/-130MPa) were also found to be statistically stronger than the posterior attachments (90.8+/-64.9MPa). These results can be used to help design tissue-engineered replacement menisci and their insertions and show the differences in material properties between attachments, as well as within an attachment., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Purpose: Our purpose was to evaluate the effect of meniscectomy and meniscal allograft transplant on anterior cruciate ligament (ACL) and knee biomechanics., Methods: A differential variable reluctance transducer was placed in the ACL of 10 human cadaveric knees to record strain. Tibial displacement from a neutral reference was recorded relative to the position of the femur. Testing was performed at 30 degrees, 60 degrees, and 90 degrees of knee flexion. Six cycles of anterior-posterior loads were applied to the limit of 150 N. After a testing cycle, a medial meniscectomy was performed and the testing cycle was repeated. A meniscal allograft transplant was performed, and a final testing cycle was conducted. ACL strain and tibial displacement in the meniscectomy and meniscal allograft states were compared with the intact-knee state., Results: Tibial displacement after meniscectomy significantly increased at all angles. The meniscal allograft transplant restored tibial displacement to normal values at 30 degrees and 90 degrees. ACL strain increased significantly after meniscectomy at 60 degrees and 90 degrees of flexion, and meniscal allograft transplant returned the strain values to normal at 60 degrees and 90 degrees., Conclusions: In most cases medial meniscectomy produced a significant increase in tibial displacement relative to the femur, and meniscal allograft transplantation restored displacement values to normal. Meniscectomy increased ACL strain and meniscal allograft transplant restored strain values to normal in 2 of 3 tested flexion angles., Clinical Relevance: The absence of the medial meniscus exposes the ACL to increased strain, whereas meniscal allograft lowered the strain on the native ACL. This could have implications for those patients undergoing ACL reconstruction who have concomitant removal of the medial meniscus., ((c) 2010 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective: To study the stress distributions in normal and osteoarthritic knee joints using the finite element method (FEM)., Material and Method: Three normal and three varus knee joints are included in the study. Computed tomography (CT) images of the lower extremities are used to create 3D geometric models consisting of bones, articular cartilages, menisci, and knee ligaments. Each of the lower extremities includes the femur, tibia, fibula, and talus. Each 3D geometric model is adjusted to the normal standing configuration with the help of its corresponding 2D radiographic image. After that, 3D finite element (FE) models are created from the adjusted 3D geometric models. FEM is then used to obtain stress distributions on the articular cartilages. In the analysis, the displacements on the posterior calcaneal articular surface of the talus are fully fixed. A vertical concentrated force equal to the body weight is applied at the femoral head., Results: In the normal knee joints, the maximum normal stresses on the articular cartilages in the lateral compartments are always higher than those in the medial compartments. In the varus knee joints, the opposite results are observed. However, in each normal knee joint, the stress distribution on the whole articular cartilage is moderately uniform. On the contrary, in each varus knee joint, comparatively high magnitudes of the normal stress are found on a large area of the articular cartilage in the medial compartment., Conclusion: Varus knee joints have higher stresses in the medial compartments while normal knee joints have higher stresses in the lateral compartments. This pilot study shows that FE studies are comparable to cadaveric studies. FEM can be used as an alternative method for studying and examining knee joints of patients.

Tibiofemoral compression causes circumferential tension in the knee meniscus, which is transferred to the tibial bone at the anterior and posterior attachments. The objective of the study was to measure the resulting tensile forces at the horn attachment in a porcine model. The anterior horn attachment of the porcine medial meniscus (n = 10) was separated from the surrounding bone with a core reamer. A force transducer was installed such that tensile forces acting upon the now mobile horn attachment could be measured. The tibiofemoral joint was loaded in compression, starting at a preload of 30 N, with three 150-N increments, giving 180, 330, and 480 N load. Flexion angles of 0, 30, and 60 degrees were investigated. The average resultant tension at the horn attachment was 26.3, 40.6, and 55.4 N with full extension, 29.2, 47.8, and 62.2 N at 30 degrees flexion and 30.1, 49.6, and 68.1 N at 60 degrees flexion. The tibiofemoral compression had a significant effect on the tension (p < 0.001), whereas no influence of the flexion angle was found (p = 0.291). The study demonstrates that tibiofemoral compressive loads cause considerable tensile forces at the anterior meniscal horn attachment. The data are of interest for models of the repair or replacement of the knee menisci.

Menisci and articular cartilage are easily injured but difficult to repair. Both tissues are structures of low cellular density. The cells are highly differentiated and specialised, with a limited capacity for proliferation. The main effects of growth factors on chondrocytes are stimulation of the extracellular cartilage matrix and inhibition and activation of proteases. Growth factors with anabolic effects promoting chondrogenesis and maintenance of the phenotype of the chondrocyte could be useful in the treatment of injured cartilage or meniscus. An important aspect of treatment with growth factors is their insertion into suitable scaffolds. Ongoing research is focusing on the repair of defects in articular cartilage with hyaline tissue instead of fibrocartilage, and the repair of meniscal lesions with a stronger fibrocartilage. This article examines the latest advances made in this field of regenerative medicine., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Objective: A narrative review describing the assessment of osteoarthritis (OA) progression, and more specifically the risk factors which assist in delineating strata of individuals at greatest risk for more rapid progression., Design: A narrative review based on selected recent medical literature., Results: With little currently available in the treatment of this disease, better understanding of responsive and valid endpoints is essential to identifying potential new interventions for treatment of OA. Efforts to stratify those at greatest risk for progression can use a number of systemic or local risk factors that may assist in delineating populations at greater risk for progression., Conclusions: Current data suggests that stratification of risk is feasible to ascertain those at risk for rapid progression using a number of different metrics including knee alignment, meniscal damage, bone marrow lesions and late stage disease. Identifying persons at greatest risk for progression has important implications for clinical trial planning and can enhance study efficiency.

Objective: The magnetic resonance (MR) T2 value of the cartilage, which has been shown in the articular cartilage to correlate with collagen fiber orientation and water content, may be helpful for early detection of chondropathy. However, the measurement and significance of MR T2 value for knee meniscus have not been well established. The purpose of this study was to investigate whether the MR T2 values in the diverse zones of the posterior horn of the knee meniscus differ between sexes in a young healthy population., Method: Twenty healthy volunteers, 10 men and 10 women (aged from 22 to 32 years), were enrolled for MR imaging of the right knee menisci. The T2 values of the posterior horns of the medial and lateral knee menisci were measured for the white zone, red/white zone, and red zone on images acquired with fat-suppressed multislice turbo spin-echo sequence at 3.0 T., Results: The T2 value, with medial and lateral menisci considered together, increased significantly from the inner white zone (T2=8.02+/-0.60 ms), to the red/white zone (T2=8.78+/-0.99 ms), and to the outer red zone (T2=12.22+/-0.92 ms) of the posterior horns of the menisci (P<0.001). A generalized estimating equation method and multiple linear regression model showed that the T2 values averaged for the medial and lateral menisci together in the red and red/white zones were significantly lower in men than in women by 1.320 ms (P=0.002) and 0.865 ms (P<0.001), respectively, while the white zone showed no significant difference (P=0.694) between men (8.08+/-0.63 ms) and women (7.98+/-0.60 ms)., Conclusion: Zonal and sex differences in the MR T2 values in the posterior horns of the knee menisci exist in the young healthy population. These differences may be associated with sex differences in the occurrence of knee osteoarthritis.

The fibrocartilagenous knee menisci are situated between the femoral condyles and tibia plateau and are primarily anchored to the tibia by means of four attachments at the anterior and posterior horns. Strong fixation of meniscal attachments to the tibial plateau provide resistance to extruding forces of the meniscal body, allowing the menisci to assist in load transmission from the femur to the tibia. Clinically, tears and ruptures of the meniscal attachments and insertion to bone are rare. While it has been suggested that the success of a meniscal replacement is dependent on several factors, one of which is the secure fixation and firm attachment of the replacement to the tibial plateau, little is known about the material properties of meniscal attachments and the transition in material properties from the meniscus to subchondral bone. The objective of this study was to use nanoindentation to investigate the transition from meniscal attachment into underlying subchondral bone through uncalcified and calcified fibrocartilage. Nanoindentation tests were performed on both the anterior and posterior meniscal insertions to measure the instantaneous elastic modulus and elastic modulus at infinite time. The elastic moduli were found to increase in a bi-linear fashion from the external ligamentous attachment to the subchondral bone. The elastic moduli for the anterior attachments were consistently larger than those for the matching posterior attachments at similar indentation locations. These results show that there is a gradient of stiffness from the superficial zones of the insertion close to the ligamentous attachment into the deeper zones of the bone. This information will be useful in the continued development of successful meniscal replacements and understanding of fixation of the replacements to the tibial plateau.

Introduction: The ultimate goal after meniscus damage is the preservation of the original meniscal tissue, which is often impossible due to the limited healing capacity of meniscal lesions, especially in the avascular zone. Factors produced by endothelial cells of meniscal vessels may contribute to better wound healing in vascularized zones. We therefore investigated the expression of different angiogenic factors, growth hormones and cytokines in human fibrochondrocytes and in fibrochondrocytes upon co-culture with endothelial cells, to examine mechanisms of repair of meniscal injury in more detail and to investigate the potential use of endothelial cells in co-cultures for autologous meniscal repair utilizing tissue engineering technology., Materials and Methods: Gene expression of SMAD-4, iNOS, IL-1beta, VEGF, MMP-1, MMP-3, MMP-13, aggrecan, biglycan, vimentin, collagen-I, -II, -III, -IV, -VI, -X, -XVIII, angiopoietin-1, angiopoietin-2, and thrombostatin-1 were investigated in fibrochondrocytes in comparison to cells in co-culture with human umbilical vein endothelial cells (HUVEC). The expression of endostatin was enumerated in cell supernatants. A proliferation assay was used to investigate the mitotic activity of the cells., Results: In presence of HUVEC, meniscal fibrochondrocytes expressed SMAD-4, iNOS, IL-1beta, VEGF, MMP-1, MMP-3, MMP-13, aggrecan, biglycan, vimentin, collagen-I, -II, -III, -VI, and -XVIII at rates comparable to cells without HUVECs. Note that the expression of endostatin was significantly higher in the co-culture when compared to the separate fibrochondrocyte cultures and the proliferation rate of endothelial cells was significantly decreased in co-culture., Conclusion: We conclude that the expression of the anti-angiogenic factor endostatin increased in the fibrochondrocytes. This may limit the regeneration capacities of meniscal injury in vivo.

Meniscus transplantation is indicated for persistent pain in a meniscectomized knee. Currently, grafts are prepared aseptically, which provides limited protection against donor-derived infection. The performance of a novel, sterilized meniscus was compared with an aseptically prepared one in an experimental model. Twenty-two sheep were divided into three groups: aseptic meniscal allograft, sterile meniscal allograft, and medial meniscectomy. Animals were euthanized 2 and 4 months after surgery. Meniscal assessments included cell viability, histology, and biomechanical testing. Articular cartilage was evaluated through histology and Outerbridge scoring. Aseptic and sterile allografts had cell viabilities of 59.7% and 58.7%, respectively, at 4 months, which was less than native controls. Grafts had decreased compressive strength at 4 months compared with their preimplantation moduli and were weaker than native menisci. In operated knees, the tibial plateau had more severe degenerative changes, although Outerbridge scores were similar between operated groups. Overall, the allografts were similar in their cellularity and biomechanical properties but were inferior to the native tissue at these end points. The severity of chondral damage in the allograft knees could not be distinguished from meniscectomized joints. The sterilization process does not appear to compromise tissue integrity and provides additional allograft safety.

Background: Although the use of meniscal allografts to replace severely damaged or absent menisci is commonplace, little is known about the effects of donor age on the biochemical and biomechanical properties of human menisci., Hypothesis: The mechanical and biochemical properties of human medial and lateral menisci from donors less than 45 years of age do not vary with donor age., Study Design: Controlled laboratory study., Methods: Thirty-three lateral and 25 medial menisci from 34 donors (26 male and 8 female) ranging from 15 to 44 years of age were harvested and immediately stored at -80 degrees C. The outer third of each meniscus was subjected to static and dynamic tensile analysis. In addition, the biochemical composition (collagen, proteoglycan, and water content) of these samples was analyzed., Results: There was no correlation between donor age and static tensile stiffness for either the lateral (R(2) = .003) or medial (R(2) = .002) meniscus. Likewise, there was no correlation between donor age and dynamic tensile modulus for either the lateral or medial meniscus. Although there was a weak, positive correlation between water content and age in both lateral (R(2) = .22) and medial (R(2) = .25) menisci, there was no effect of age on collagen or proteoglycan content. There were no differences (P > .05) between female and male menisci in any of the measured biomechanical or biochemical parameters tested., Conclusion: The tensile properties, as well as the collagen and proteoglycan content, of menisci from donors less than 45 years of age were not age dependent., Clinical Relevance: The age of the donor does not appear to affect the initial tensile properties of menisci from donors less than 45 years of age.

Osteoarthritis in the knees, which can be caused by meniscal defect, constitutes an increasingly common medical problem. Repair for massive meniscal defect remains a challenge owing to a lack of cell kinetics for the menisci precursors in knee joint. The synovium plays pivotal roles during the natural course of meniscal healing and contains mesenchymal stem cells (MSCs) with high chondrogenic potential. Here, we investigated whether intra-articular injected synovium-MSCs enhanced meniscal regeneration in rat massive meniscal defect. To track the injected cells, we developed transgenic rats expressing dual luciferase (Luc) and LacZ. The cells derived from synovium of the rats demonstrated colony-forming ability and multipotentiality, both characteristics of MSCs. Hierarchical clustering analysis revealed that gene expression of meniscal cells was closer to that of synovium-MSCs than to that of bone marrow-MSCs. Two to 8 weeks after five million Luc/LacZ+ synovium-MSCs were injected into massive meniscectomized knee of wild-type rat, macroscopically, the menisci regenerated much better than it did in the control group. After 12 weeks, the regenerated menisci were LacZ positive, produced type 2 collagen, and showed meniscal features by transmission electron microscopy. In in-vivo luminescence analysis, photons increased in the meniscus-resected knee over a 3-day period, then decreased without detection in all other organs. LacZ gene derived from MSCs could not be detected in other organs except in synovium by real-time PCR. Synovium-MSCs injected into the massive meniscectomized knee adhered to the lesion, differentiated into meniscal cells directly, and promoted meniscal regeneration without mobilization to distant organs.

The tibiofemoral articulating interfaces of six high flexion knee designs were examined using a standard testing protocol developed by Harris et al. [J Biomech 32:951-958 (1999)] to investigate the polyethylene insert contact areas and pressures. A load of 3600 N was applied for 10 s at 0, 30, 60, 90, 110, 135 and 155 degrees of flexion. Contact areas and pressures at the femoral-polyethylene insert interface were measured with a I-scan 4000 system. Up to 110 degrees of flexion, the VANGUARD RP HI-FLEX showed the highest contact area and lowest pressure. At the deep flexion angles, contact area decreased and contact pressure increased significantly in all knees. The NexGen series showed a constant contact area throughout the various flexion angles. In general, all high flexion knees could result in almost point contact in an extremely high range of motion.

Purpose: The aims of this study were to determine: (1) the kinematic effect of subtotal medial meniscectomy on the anterior cruciate ligament (ACL)-deficient knee and (2) the effect of ACL reconstruction on kinematics of the knee with combined ACL deficiency and subtotal medial meniscectomy under anterior tibial and simulated quadriceps loads., Methods: Eight human cadaveric knees were sequentially tested using a robotic testing system under 4 conditions: intact, ACL deficiency, ACL deficiency with subtotal medial meniscectomy, and single-bundle ACL reconstruction using a bone-patellar tendon-bone graft. Knee kinematics were measured at 0 degrees, 15 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion under an anterior tibial load of 130 N and a quadriceps muscle load of 400 N., Results: Subtotal medial meniscectomy in the ACL-deficient knee significantly increased anterior and lateral tibial translations under the anterior tibial and quadriceps loads (P < .05). These kinematic changes were larger at high flexion (>or=60 degrees) than at low flexion angles. ACL reconstruction in knees with ACL deficiency and subtotal medial meniscectomy significantly reduced the increased anterior tibial translation, but could not restore anterior translation to the intact level with differences ranging from 2.6 mm at 0 degrees to 5.5 mm at 30 degrees of flexion. ACL reconstruction did not significantly affect the medial-lateral translation and internal-external tibial rotation in the presence of subtotal meniscectomy., Conclusions: Subtotal medial meniscectomy in knees with ACL deficiency altered knee kinematics, especially at high flexion angles. ACL reconstruction significantly reduced the increased tibial translation in knees with combined ACL deficiency and subtotal medial meniscectomy, but could not restore the knee kinematics to the intact knee level., Clinical Relevance: This study suggests that meniscus is an important secondary stabilizer against anterior and lateral tibial translations and should be preserved in the setting of ACL reconstruction for restoration of optimal knee kinematics and function.

The menisci of the knee play a significant role in the complex biomechanics of the joint and are critically important in maintaining articular cartilage health. While a general form-function relationship has been identified for the structural orientation of the extra-cellular matrix of the meniscus, the role of individual biochemical components has yet to be fully explored. To determine if correlations exist between the dynamic and static compressive modulus of human menisci and their major extra-cellular matrix constituents (collagen, glycosoaminoglycan and water content), 12 lateral and 11 medial menisci from 13 adult donors were examined. The results showed that in dynamic compression at high loading frequencies (0.1-1 Hz) the menisci behave as a rubber-like elastic material while at lower frequencies (0.01-0.03 Hz) significant viscous dissipation occurs. While regional variations in compressive moduli and extra-cellular matrix composition were observed, the magnitude of both dynamic and static compressive moduli were found to be insensitive to collagen content (p>0.4). However, this magnitude was found to significantly increase with increasing glycosaminoglycan content (p<0.001) and significantly decrease with increasing water content (p<0.001). The results of this study identify significant relationships between the viscoelastic behavior of the meniscus and its extra-cellular matrix composition.

Meniscal healing especially in the inner avascular region has always been a major challenge. In this study we investigated the potential for platelet derived growth factor-AB (PDGF-AB) to promote meniscal tissue regeneration in the inner (avascular), middle, and outer (vascular) zones of the meniscus. Various concentrations of PDGF-AB were tested on sheep meniscal cell cultures. We used the radioactive thymidine uptake assay to assess cell proliferation, and the radioactive sulphur and proline uptake assays and Blyscan assay to assess matrix formation. In general, PDGF-AB stimulated both cell proliferation and matrix formation by cells from all meniscal zones. PDGF-AB at a concentration of 100 ng/ml increased cell proliferation and matrix formation by eight and four fold respectively, by fibrochondrocytes cultured from all meniscal zones (p<0.001). These results indicate that fibrochondrocytes present within the avascular region of the meniscus have the ability to proliferate and form new matrix when exposed to anabolic cytokines such as PDGF-AB.

The meniscus is a fibrocartilaginous tissue uniquely adapted to enable load transmission in the knee. Although the meniscus was once considered a useless remnant of joint formation, removal of all or part of the meniscus initiates osteoarthritis. Surgical repair methods focus on fragment stabilization or biologic enhancement of healing. An alternative approach based on tissue-engineering principles involves the development of new materials for implantation. Our meniscus tissue-engineering efforts aim to recapitulate the architectural features and mechanical anisotropies essential to native tissue function. We use a novel scaffold production technology called electrospinning, in which organized three-dimensional arrays of ultrafine biodegradable fibers are generated. Using these scaffolds as micropatterns for directed growth, we have generated constructs with mechanical properties and architectural features comparable to native meniscus. This review details our progress and outlines the remaining hurdles that must be addressed to translate this work into clinical implementation.

Collagen fibrils networks in knee cartilage and menisci change in content and structure from a region to another. While resisting tension, they influence global joint response as well as local strains particularly at short-term periods. To investigate the role of fibrils networks in knee joint mechanics and in particular cartilage response, a novel model of the knee joint is developed that incorporates the cartilage and meniscus fibrils networks as well as depth-dependent properties in cartilage. The joint response under up to 2000N compression is investigated for conditions simulating the absence in cartilage of deep fibrils normal to subchondral bone or superficial fibrils parallel to surface as well as localized split of cartilage at subchondral junction or localized damage to superficial fibrils at loaded areas. Deep vertical fibrils network in cartilage play a crucial role in stiffening (by 10%) global response and protecting cartilage by reducing large strains (from maximum of 102% to 38%), in particular at subchondral junction. Superficial horizontal fibrils protect the tissue mainly from excessive strains at superficial layers (from 27% to 8%). Local cartilage split at base disrupts the normal function of vertical fibrils at the affected areas resulting in higher strains. Deep fibrils, and to a lesser extent superficial fibrils, play dominant mechanical roles in cartilage response under transient compression. Any treatment modality attempting to repair or regenerate cartilage defects involving partial or full thickness osteochondral grafts should account for the crucial role of collagen fibrils networks and the demanding mechanical environment of the tissue.

The menisci of the knee act primarily to redistribute contact force across the tibio-femoral articulation. This meniscal function is achieved through a combination of the material, geometry and attachments of the menisci. The main ligaments that attach the menisci to the tibia (insertional ligaments, deep medial collateral ligament), the femur (meniscofemoral ligaments, deep medial collateral ligament) and each other (the anterior intermeniscal ligament) are the means by which the contact force between tibia and femur is distributed into hoop stresses in the menisci to reduce contact pressure at the joint. This means that the functional biomechanics of the menisci cannot be considered in isolation and should be considered as the functional biomechanics of the meniscus-meniscal ligament construct. This article presents the current knowledge on the anatomy and functional biomechanics of the meniscus and its associated ligaments. Much is known about the function of the meniscus-meniscal ligament construct; however, there still remain significant gaps in the literature in terms of the properties of the anterior intermeniscal ligament and its function, the properties of the insertional ligaments, and the most appropriate ways to reconstruct meniscal function surgically.

Meniscus is a well innervated tissue with four types of receptors. These receptors are mainly concentrated at the anterior and posterior horns. Although they are intended to be a part in reflex arc, this function has not been thoroughly evaluated. We hypothesized that electrical stimulation of the normal meniscus would elicit electromyographic activity of the hamstring muscle via the reflex arc. Five adult domestic male rabbits were used in this study. Under general anesthesia, knee arthrotomy and thigh dissection were done to expose medial meniscus and semimembranosus muscle. Menisci were stimulated by Teflon-coated bipolar needle electrodes. Needles were placed in the posterior horn of the medial menisci. Two Teflon-coated monopolar needle electrodes were placed in semimembranosus muscle. A four-channel electromyograph was used for recording. Two different potentials were recorded from the target muscle. The first response had a very short distal latency and its amplitude was changing in accordance with the strength of the stimulus, suggesting that this response was being elicited by direct muscle stimulation. The second delayed response with less amplitude also appeared in some traces. The latency and the amplitude of this second response were fairly stable stating that this delayed response was being generated by a reflex pathway and seen in all subjects.

Little is known about in vivo menisci loads and displacements in the knee during strenuous activities. A new method that combines high-speed kinematics measured with biplane dynamic Roentgen stereogrammetric analysis (DRSA) and a subject-specific finite element (FE) model for studying in vivo meniscal behavior is presented here. Further model calibration in a very controlled uniaxial low and high-rate compression loading condition is presented by comparing the model behavior against the measured high-accuracy menisci DRSA kinematics and direct tibio-femoral pressure measurement from a K-scan sensor. It is apparent that certain model aspects such as removing of the pressure sensor from the model can result in relatively large errors (14%) in contact parameters that are not reflected in the change of the measured meniscal kinematics. Changing mesh size to 1mm by 1mm elements increased the magnitude of all but one of the contact variables by up to 45%. This local validation using accurate localized patient-specific geometry and meniscal kinematics was needed to enhance model fidelity at the level of contact between menisci and cartilage.

Cells within fibrocartilaginous tissues, including chondrocytes and fibroblasts of the meniscus, ligament, and tendon, regulate cell biosynthesis in response to local mechanical stimuli. The processes by which an applied mechanical load is transferred through the extracellular matrix to the environment of a cell are not fully understood. To better understand the role of mechanics in controlling cell phenotype and biosynthetic activity, this study was conducted to measure strain at different length scales in tissue of the fibrocartilaginous meniscus of the knee joint, and to define a quantitative parameter that describes the strain transferred from the far-field tissue to a microenvironment surrounding a cell. Experiments were performed to apply a controlled uniaxial tensile deformation to explants of porcine meniscus containing live cells. Using texture correlation analyses of confocal microscopy images, two-dimensional Lagrangian and principal strains were measured at length scales representative of the tissue (macroscale) and microenvironment in the region of a cell (microscale) to yield a strain transfer ratio as a measure of median microscale to macroscale strain. The data demonstrate that principal strains at the microscale are coupled to and amplified from macroscale principal strains for a majority of cell microenvironments located across diverse microstructural regions, with average strain transfer ratios of 1.6 and 2.9 for the maximum and minimum principal strains, respectively. Lagrangian strain components calculated along the experimental axes of applied deformations exhibited considerable spatial heterogeneity and intersample variability, and suggest the existence of both strain amplification and attenuation. This feature is consistent with an in-plane rotation of the principal strain axes relative to the experimental axes at the microscale that may result from fiber sliding, fiber twisting, and fiber-matrix interactions that are believed to be important for regulating deformation in other fibrocartilaginous tissues. The findings for consistent amplification of macroscale to microscale principal strains suggest a coordinated pattern of strain transfer from applied deformation to the microscale environment of a cell that is largely independent of these microstructural features in the fibrocartilaginous meniscus.

Studying the mechanics of the knee joint has direct implications in understanding the state of human health and disease and can aid in treatment of injuries. In this work, we developed an axisymmetric model of the human knee joint using finite element method, which consisted of separate parts representing tibia, meniscus and femoral, and tibial articular cartilages. The articular cartilages were modeled as three separate layers with different material characteristics: top superficial layer, middle layer, and calcified layer. The biphasic characteristic of both meniscus and cartilage layers were included in the computational model. The developed model was employed to investigate several aspects of mechanical response of the knee joint under external loading associated with the standing posture. Specifically, we studied the role of the material characteristic of the articular cartilage and meniscus on the distribution of the shear stresses in the healthy knee joint and the knee joint after meniscectomy. We further employed the proposed computational model to study the mechanics of the knee joint with an artificial meniscus. Our calculations suggested an optimal elastic modulus of about 110 MPa for the artificial meniscus which was modeled as a linear isotropic material. The suggested optimum stiffness of the artificial meniscus corresponds to the stiffness of the physiological meniscus in the circumferential direction.

Studies of the load transfer role of the meniscus have been limited to static experimental and analytical approaches. The objective of this study was to develop an experimental technique to allow the contact pressures on the tibial plateau of cadaveric knees to be measured under dynamic physiological loads. Accordingly, we adapted a load-controlled knee joint simulator to accept a cadaveric sheep knee, programmed the simulator with sheep gait kinematics data, and utilized a pressure sensor array to measure the contact pressure distribution on the lateral tibial plateau during gait. The technique was applied to six sheep knees that were tested intact and after meniscectomy. Meniscectomy resulted in a 267% increase in average contact pressure, a 117% increase in peak contact pressure, and an 80% decrease in contact area, all measured at the point of maximum peak contact stress in the gait cycle. It is envisaged that the experimental model herein developed will allow for the screening of candidate materials prior to more expensive and time-consuming animal models.

The purpose of this study was to assess transplantation of regenerated menisci using scaffolds from normal allogeneic menisci and bone-marrow-derived mesenchymal stromal cells (BM-MSCs) of rats. We reported that scaffolds derived from normal menisci seeded with BM-MSCs in vitro could form meniscal tissues within 4 weeks. Then, we hypothesized that our tissues could be more beneficial than allogeneic menisci regarding early maturation and chondroprotective effect. Bone marrow was aspirated from enhanced green fluorescent protein transgenic rats. BM-MSCs were isolated and seeded onto scaffolds which were prepared from Sprague-Dawley rat menisci. After 4 weeks in coculture, the tissues were transplanted to the defect of menisci. Repopulation of BM-MSCs and expression of extracellular matrices were observed in the transplanted tissues at 4 weeks after surgery. At 8 weeks, articular cartilage in the cell-free group was more damaged compared to that in the cell-seeded group or the meniscectomy group.

The axial and radial compressive moduli of the human meniscus are important material properties in tibiofemoral joint models, but they have not been determined previously for fresh-frozen tissue. Our goals were to measure the moduli at equilibrium and at a physiological strain rate, to determine whether the axial and radial compressive moduli are equal for each type of loading, and to determine whether they depend on the region (i.e., anterior, middle, posterior) of the meniscus. Samples from each region from 10 fresh-frozen human medial menisci were tested in unconfined compression at four strain levels (3%, 6%, 9%, and 12%) at 32%/s, a strain rate determined to be physiologically relevant to walking, and then allowed to reach equilibrium in stress relaxation. At equilibrium, the axial and radial compressive moduli at 12% strain were 83.4 kPa and 76.1 kPa, respectively (p = 0.58), whereas at the physiological strain rate, the axial and radial compressive moduli at 12% strain were 718 kPa and 605 kPa, respectively (p = 0.61). At the physiological strain rate, the modulus increased with increasing strain (79.2 kPa at 3% strain vs. 662 kPa at 12% strain) and the modulus in the anterior region (1,048 kPa at 12% strain) was significantly greater than that in the posterior region (329 kPa at 12% strain) (p = 0.04). Our study supports a plane of isotropy for the material properties of meniscal tissue. However, the material behavior is strongly nonlinear because the compressive modulus is several orders of magnitude smaller than previously reported values for tensile modulus. Further, the compressive modulus depends on the activity of interest (i.e., static such as standing or dynamic such as walking) due to viscoelastic effects, the strain level, and the region of the tissue.

Objective: The aim of the study was to investigate the use of a novel hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Two different surgical implantation techniques in a sheep model were evaluated., Methods: Twenty-four skeletally mature sheep were treated with total medial meniscus replacements, while two meniscectomies served as empty controls. The animals were divided into two groups: cell-free scaffold and scaffold seeded with autologous chondrocytes. Two different surgical techniques were compared: in 12 animals, the implant was sutured to the capsule and to the meniscal ligament; in the other 12 animals, also a transtibial fixation of the horns was used. The animals were euthanized after 4 months. The specimens were assessed by gross inspection and histology., Results: All implants showed excellent capsular ingrowth at the periphery. Macroscopically, no difference was observed between cell-seeded and cell-free groups. Better implant appearance and integrity was observed in the group without transosseous horns fixation. Using the latter implantation technique, lower joint degeneration was observed in the cell-seeded group with respect to cell-free implants. The histological analysis indicated cellular infiltration and vascularization throughout the implanted constructs. Cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs., Conclusion: The current study supports the potential of a novel HYAFF/polycaprolactone scaffold for total meniscal substitution. Seeding of the scaffolds with autologous chondrocytes provides some benefit in the extent of fibrocartilaginous tissue repair.

The purpose of this study was to clarify meniscal displacement and cartilage-meniscus contact behavior in a full extension position and a deep knee flexion position. We also studied whether the meniscal translation pattern correlated with the tibiofemoral cartilage contact kinematics. Magnetic resonance (MR) images were acquired at both positions for 10 subjects using a conventional MR scanner. Subjects achieved a flexion angle averaging 139 degrees +/- 3 degrees. Both medial and lateral menisci translated posteriorly on the tibial plateau during deep knee flexion. The posterior translation of the lateral meniscus (8.2 +/- 3.2 mm) was greater than the medial (3.3 +/- 1.5 mm). This difference was correlated with the difference in tibiofemoral contact kinematics between medial and lateral compartments. Contact areas in deep flexion were approximately 75% those at full extension. In addition, the percentage of area in contact with menisci increased significantly due to deep flexion. Our results related to meniscal translation and tibio-menisco-femoral contact in deep knee flexion, in combination with information about force and pressure in the knee, may lead to a better understanding of the mechanism of meniscal degeneration and osteoarthritis associated with prolonged kneeling and squatting., ((c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Introduction: Cyclic testing may provide a more valid depiction of how arthroscopic meniscal repairs will withstand the forces of activities of daily living (ADLs) and therapeutic exercises early post-surgery than single cycle load to failure testing. This study compared the meniscal fixation provided by vertically or horizontally placed FasT-Fix devices to horizontally placed RapidLoc devices under submaximal cyclic test conditions., Materials and Methods: Eighteen human cadaveric menisci were divided into three groups of six specimens. A scalpel was used to create a 2 cm lesion at 3 mm from the outer edge of the posterior third of each specimen. Merselene tape loops were placed around each side of the lesion and the tears were repaired using two vertical FasT-Fix, two horizontal FasT-Fix, or two RapidLoc devices. Cyclic testing (5-50 N at 1 Hz for 500 cycles) was performed on a servo hydraulic device. One-way ANOVA and Scheffe post-hoc tests were used to evaluate group differences (P < 0.05)., Results: The vertical FasT-Fix group had less displacement over the initial ten loading cycles compared to the RapidLoc group (P = 0.004), but did not differ from the horizontal FasT-Fix group (P = 0.07). At 50, 100, 200, 300, 400, and 500 cycles, the vertical FasT-Fix group had less displacement than the horizontal FasT-Fix or RapidLoc groups (P < or = 0.004). At each interval the vertical FasT-Fix group had greater relative stiffness than the other groups (P < or = 0.009)., Conclusions: The vertical FasT-Fix group had comparatively less displacement (primarily repair site gapping) and greater relative stiffness.

Damage or loss of the meniscus is associated with progressive osteoarthritic degeneration of the knee joint. Injured and degenerative joints are characterized by elevated levels of the pro-inflammatory cytokine interleukin-1 (IL-1), which with prolonged exposure can induce catabolic and anti-anabolic activities that inhibit tissue repair. We used an in vitro model system to examine the hypotheses that acute exposure to IL-1 inhibits meniscal repair, and that an IL-1-mediated increase in matrix metalloproteinase (MMP) activity is associated with the inhibition of repair. Integrative tissue repair was studied between concentric explants of porcine medial menisci that were treated with IL-1alpha acutely (100 pg/mL for 1 or 3 days) or chronically (100 pg/mL for entire culture duration). After 14 and 28 days in culture, biomechanical testing, cell viability, and histology were performed to assess meniscal repair. Total specific MMP activity in the culture media was measured using a quenched fluorescent substrate. As little as 1 day of IL-1 exposure significantly reduced shear strength, cell accumulation, and tissue repair compared to controls. IL-1 exposure for 1 or 3 days significantly increased MMP activity that subsided by day 9. With chronic IL-1 exposure, MMP activity remained elevated for the duration of culture and was negatively correlated with repair strength. Our study shows that short-term exposure to physiologically relevant concentrations of IL-1 significantly reduces meniscal repair in vitro, and thus may potentially inhibit the intrinsic repair response in vivo. The suppression of IL-1 or MMP expression and/or activity warrant investigation as potential strategies for promoting meniscal repair.

This in vivo magnetic resonance imaging study evaluated the deformation of the meniscal posterior horn during loading. Images of the medial and lateral meniscus were obtained in 20 normal knees in 0 degrees and 30 degrees of flexion, and the height of the posterior horn of both menisci was measured. Mean height of the posterior horn of the medial meniscus under no load and load equal to 50% and 100% body weight was 6.8, 6.3, and 6 mm, respectively (P<.05). Mean height of the posterior horn of the lateral meniscus under no load and load equal to 50% and 100% body weight was 7.6, 7.2, and 6.9 mm, respectively (P<.05). Knee position (0 degree versus 30 degrees of flexion) at a constant load resulted in no significant change in height. These results show height of the posterior horn of the medial and lateral meniscus decrease with increasing loading and angle of knee flexion.

Use of computational models with kinematic boundary conditions to study the knee joint contact behavior for normal and pathologic knee joints depends on an understanding of the impacts of kinematic uncertainty. We studied the sensitivities of tibio-menisco-femoral joint contact behavior to variations in knee kinematics using a finite element model (FEM) with geometry and kinematic boundary conditions derived from sequences of magnetic resonance (MR) images. The MR images were taken before and after axial compression was applied to the knee joint of a healthy subject. A design of experiments approach was used to study the impact of the variation in knee kinematics on the contact outputs. We also explored the feasibility of using supplementary hip images to improve the accuracy of knee kinematics. Variations in knee kinematics (0.25mm in medial-lateral, 0.1mm in anterior-posterior and superior-inferior translations, and 0.1 degrees in flexion-extension and varus-valgus, 0.25 degrees in external-internal rotations) caused large variations in joint contact behavior. When kinematic boundary conditions resulted in close approximations of the model-predicted joint contact force to the applied force, variations in predictions of contact parameters were also reduced. The combination of inferior-superior and medial-lateral translations accounted for over 70% of variations for all the contact parameters examined. The inclusion of hip images in kinematic calculations improved knee kinematics by matching the femoral head position. Our findings demonstrate the importance of improving the accuracy and precision of knee kinematic measurements, especially when utilized as an input for finite element models.

Little quantitative data is available on the structure of meniscal attachments. Therefore, as an aid to designing meniscal replacements as well as a possible explanation for mechanical behavior, this study was designed to further the knowledge of the microstructure and biochemistry of native meniscal attachments. Bovine medial meniscal attachments (the external ligamentous portion as well as the transition zones at the bony insertion) were removed and prepared for microstructural evaluation. After embedding in paraffin, the samples were sliced on a microtome and stained for quantitative analysis. The anterior and posterior insertion sites are known to contain three zones: subchondral bone, calcified fibrocartilage, and uncalcified fibrocartilage. Additionally, others have shown that the anterior insertion site contains a ligamentous zone. The insertion zones were further divided into proximal, middle, and distal zones. The posterior attachment's insertion site had a significantly greater thickness of interdigitations, subchondral bone, uncalcified fibrocartilage, and calcified fibrocartilage zone thickness compared to the anterior attachment insertion. The anterior attachment's insertion had the greatest GAG fraction in each zone when compared to the posterior attachment's insertion. GAG fraction decreased from the meniscus to the subchondral bone. Both GAG fraction and normalized thickness varied within a given zone, decreasing from the distal to proximal regions in both the anterior and posterior attachments' insertion zones. Crimp frequency of the collagen fibrils in the external ligamentous portion of the tissue was homogeneous along the length. The findings from this study agree with previously published material property data on the medial meniscal attachments, and could be used in the future to design methods of attachment for tissue engineered replacement menisci.

The objective of this study was to determine tibiofemoral cartilage thickness distribution, and to investigate the relationship between cartilage geometry and anthropometric variables. In this study, 20 magnetic resonance examinations of the knee from normal individuals were reconstructed to provide three-dimensional models of the knee joint, including bony and cartilage surfaces. Three regions were defined on the articular surface, and the cartilage thickness distribution along each of these was determined. Statistically significant differences between femoral and tibial regions were examined using the paired Student t test in Microsoft Excel. Correlations were investigated using the correlation tool in Microsoft Excel. The average tibial cartilage thickness was found to be 2.76 mm and the average femoral cartilage thickness was 2.75 mm. Significant correlations exist between the tibia cartilage thickness and body height (R = 0.60; P < 0.05) and weight (R = 0.64; P < 0.05). Significant correlations exist between the femoral cartilage volume and the body height (R = 0.736; P < 0.01) and weight (R = 0.855; P < 0.01). It is suggested that the distribution and correlations of cartilage distribution indicate adaptation in response to mechanical loading. Information regarding cartilage thickness and volume distribution as found in this study may be useful in diagnosing and monitoring cartilage loss in patients with degenerative joint disease.

Introduction: Meniscal injury is a risk factor for the development and progression of knee osteoarthritis, yet little is known about risk factors for meniscal pathology. Joint loading mediated via gait parameters may be associated with meniscal tears, and determining whether such an association exists was the aim of this study., Methods: Three-dimensional Vicon gait analyses were performed on the dominant knee of 20 non-osteoarthritic women, and the peak external knee adduction moment during early and late stance was determined. The degree of foot rotation was also examined when the knee adductor moment peaked during early and late stance. Magnetic resonance imaging was used to determine the presence and severity of meniscal lesions in the dominant knee., Results: The presence (P = 0.04) and severity (P = 0.01) of medial meniscal tears were positively associated with the peak external knee adduction moment during early stance while a trend for late stance was observed (P = 0.07). They were also associated with increasing degrees of internal foot rotation during late stance, independent of the magnitude of the peak external knee adduction moment occurring at that time (P = 0.03). During level walking among healthy women, the presence and severity of medial meniscal tears were positively associated with the peak external knee adduction moment. Moreover, the magnitude of internal foot rotation was associated with the presence and severity of medial meniscal lesions, independent of the peak knee adductor moment during late stance., Conclusion: These data may suggest that gait parameters may be associated with meniscal damage, although longitudinal studies will be required to clarify whether gait abnormalities predate meniscal lesions, or vice versa, and therefore whether modification of gait patterns may be helpful.

Meniscus allografting has provided relief of meniscal injuries that were previously thought irreparable. However, meniscus allograft tissue remains limited and a significant problem. To improve allograft tissue yield, decrease processing costs, and increase graft availability, this study investigated the biomechanical changes of meniscal allograft tissue frozen and thawed multiple times. Specifically, our study compared the intrinsic compressive resistances of meniscus undergoing four Freeze-Thaw cycles versus tissue undergoing a single Freeze-Thaw cycle. Seven menisci that were originally procured and processed for allografting were donated for the study. Each meniscus was segmented and samples independently underwent novel constant slow-rate compression testing, and histological and biochemical evaluation. The menisci that underwent a single Freeze-Thaw cycle demonstrated a significantly higher Young's Modulus (14 megapascals) as compared to menisci undergoing multiple Freeze-Thaw cycles (10 megapascals, p = 0.03). These results were maintained when medial and lateral menisci were compared independently. Histological and biochemical analyses supported, but did not provide an explanation for the change in intrinsic compressive resistance. From these results, transplantation of meniscal allograft tissue frozen and thawed four times may be compromised in its ability to resist compression; and thus may undermine its role in replacing native meniscal tissue., ((c) 2007 Orthopaedic Research Society.)

Scaffolds play a key role in the field of tissue engineering. Particularly for meniscus replacement, optimal scaffold properties are critical. The aim of our study was to develop a novel scaffold for replacement of meniscal tissue by means of tissue engineering. Emphasis was put on biomechanical properties comparable to native meniscus, nonimmunogenecity, and the possibility of seeding cells into and cultivating them within the scaffold (nontoxicity). For this purpose, native ovine menisci were treated in vitro in a self-developed enzymatic process. Complete cell removal was achieved and shown both histologically and electron microscopically (n = 15). Immunohistochemical reaction (MHC 1/MHC 2) was positive for native ovine meniscus and negative for the scaffold. Compared to native meniscus (25.8 N/mm) stiffness of the scaffold was significantly increased (30.2 N/mm, p < 0.05, n = 10). We determined the compression (%) of the native meniscus and the scaffold under a load of 7 N. The compression was 23% for native meniscus and 29% for the scaffold (p < 0.05, n = 10). Residual force of the scaffold was significantly lower (5.2 N vs. 4.9 N, p < 0.05, n = 10). Autologous fibrochondrocytes were needle injected and successfully cultivated within the scaffolds over a period of 4 weeks (n = 10). To our knowledge, this study is the first to remove cells and immunogenetic proteins (MHC 1/MHC 2) completely out of native meniscus and preserve important biomechanical properties. Also, injected cells could be successfully cultivated within the scaffold. Further in vitro and in vivo animal studies are necessary to establish optimal cell sources, sterilization, and seeding techniques. Cell differentiation, matrix production, in vivo remodeling of the construct, and possible immunological reactions after implantation are subject of further studies., (Copyright 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The medial and lateral menisci play important roles in knee biomechanics, kinematics, and stability. Unfortunately, these structures are prone to damage and, because of a tenuous blood supply, have great difficulty healing. Many interventions have been proposed for treatment of damaged meniscal tissue, but most surgical options are fraught with difficulties, from continued osteoarthritic degeneration to potential for disease transmission. The field of tissue engineering has made wide inroads into constructing meniscal tissue. Investigations involving collagenous tissue, meniscal fibrochondrocytes, chondrocytes, synthetic scaffolds, and gene therapy have all been reported in the literature. Despite these advances, however, more work needs to be done, including incorporating concepts and applications from other engineering disciplines, to potentiate the possibility of a tissue-engineered meniscus that approximates native tissue. In particular, the histologic, morphologic, and biomechanical properties of tissue-engineered meniscal constructs must be better understood to facilitate this goal.

The theoretical framework developed in a companion paper (Part I) is used to derive estimates of mechanical response of two meniscal cartilage specimens. The previously developed framework consisted of a constitutive model capable of incorporating confocal image-derived tissue microstructural data. In the present paper (Part II) fibre and matrix constitutive parameters are first estimated from mechanical testing of a batch of specimens similar to, but independent from those under consideration. Image analysis techniques which allow estimation of tissue microstructural parameters form confocal images are presented. The constitutive model and image-derived structural parameters are then used to predict the reaction force history of the two meniscal specimens subjected to partially confined compression. The predictions are made on the basis of the specimens' individual structural condition as assessed by confocal microscopy and involve no tuning of material parameters. Although the model does not reproduce all features of the experimental curves, as an unfitted estimate of mechanical response the prediction is quite accurate. In light of the obtained results it is judged that more general non-invasive estimation of tissue mechanical properties is possible using the developed framework.

Objective: To examine the hypotheses that increasing concentrations of interleukin-1 (IL-1) or tumor necrosis factor alpha (TNFalpha) inhibit the integrative repair of the knee meniscus in an in vitro model system, and that inhibitors of these cytokines will enhance repair., Methods: Explants (8 mm in diameter) were harvested from porcine medial menisci. To simulate a full-thickness defect, a 4-mm-diameter core was removed and reinserted. Explants were cultured for 14, 28, or 42 days in the presence of 0-1,000 pg/ml of IL-1 or TNFalpha. Explants were also cultured in the presence of IL-1 or TNFalpha with IL-1 receptor antagonist (IL-1Ra) or TNF monoclonal antibody (mAb). At the end of the culture period, biomechanical testing, cell viability, and histologic analyses were performed to quantify the extent of repair., Results: Mechanical testing revealed increased repair strength, cell accumulation, and tissue formation at the interface over time under control conditions. Pathophysiologic concentrations of both IL-1 and TNFalpha significantly decreased repair strength, cell migration, and tissue formation at the interface. The addition of IL-1Ra or TNF mAb to explants prevented the effects of IL-1 or TNFalpha, respectively., Conclusion: Our findings document that physiologically relevant concentrations of IL-1 and TNFalpha inhibit meniscal repair in vitro and therefore may also inhibit meniscal repair during arthritis or following joint injury. The finding that IL-1Ra and TNF mAb promoted integrative meniscal repair in an inflammatory microenvironment suggests that intraarticular delivery of IL-1Ra and/or TNF mAb may be useful clinically to promote meniscal healing following injury.

Arthroscopic partial meniscectomy is one of the most common orthopedic surgical procedures performed. Numerous clinical and biomechanical studies have shown the long-term consequences of the meniscus-deficient knee, which includes increased loading of the cartilage. This leads to chondromalacia, and ultimately pain and dysfunction. Few treatment options are available for the young patient with pain in the tibiofemoral compartment secondary to meniscus deficiency. Meniscal allograft transplantation is a viable treatment option in this group of patients as short-term results have shown pain relief and functional improvement. Biomechanical studies have shown that the allograft meniscal transplant functions most like a native, intact meniscus when specific surgical principles are followed. Surgical techniques for meniscal allograft transplantation have advanced along with instrumentation. An improvement in function and pain relief can be expected when strict criteria are followed in patient selection and surgical technique.