[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of the mechanical behavior of biomedical materials. 09/2009; 2(4):339-47.
[Show abstract][Hide abstract] ABSTRACT: The meniscus is an important load-bearing structure in the knee, as it provides load distribution and cushioning properties during weight-bearing activities. The compressive modulus and permeability of the meniscus is attributed to the tissue’s glycosaminoglycan (GAG) content, as charged proteoglycan side chains allow for tissue swelling and resistance to compression . The distribution of sulphated GAGs throughout the meniscus has not been thoroughly documented. Although load differs across the knee joint, few researchers have investigated medial/lateral and coronal differences in meniscal architecture and GAG distribution [2, 3]. It is hypothesized that the distribution of positive histological staining for sulfated GAGs will differ across spatial regions of rabbit menisci. Primarily, it is hypothesized that regions of the menisci that likely see higher loading will demonstrate an increase in sulfated GAG-positive staining area.
[Show abstract][Hide abstract] ABSTRACT: Following partial meniscectomy, the remaining meniscus is exposed to an altered loading environment. In vitro 20% dynamic compressive strains on meniscal tissue explants has been shown to lead to an increase in release of glycosaminoglycans from the tissue and increased expression of interleukin-1alpha (IL-1alpha). The goal of this study was to determine if compressive loading which induces endogenously expressed IL-1 results in downstream changes in gene expression of anabolic and catabolic molecules in meniscal tissue, such as MMP expression.
Relative changes in gene expression of MMP-1, MMP-3, MMP-9, MMP-13, A Disintegrin and Metalloproteinase with ThromboSpondin 4 (ADAMTS4), ADAMTS5, TNFalpha, TGFbeta, COX-2, Type I collagen (COL-1) and aggrecan and subsequent changes in the concentration of prostaglandin E(2) released by meniscal tissue in response to varying levels of dynamic compression (0%, 10%, and 20%) were measured. Porcine meniscal explants were dynamically compressed for 2h at 1Hz.
20% dynamic compressive strains upregulated MMP-1, MMP-3, MMP-13 and ADAMTS4 compared to no dynamic loading. Aggrecan, COX-2, and ADAMTS5 gene expression were upregulated under 10% strain compared to no dynamic loading while COL-1, TIMP-1, and TGFbeta gene expression were not dependent on the magnitude of loading.
This data suggests that changes in mechanical loading of the knee joint meniscus from 10% to 20% dynamic strain can increase the catabolic activity of the meniscus.
Osteoarthritis and Cartilage 06/2009; 17(6):754-60. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal of this research is to develop a 3D finite element (FE) model of a left ventricular assist device (LVAD) to predict stresses in the blood sac. The hyperelastic stress-strain curves for the segmented poly(ether polyurethane urea) (SPEUU) blood sac were determined in both tension and compression using a servo-hydraulic testing system at various strain rates. Over the range of strain rates studied, the sac was not strain rate sensitive, however the material response was different for tension versus compression. The experimental tension and compression properties were used in a FE model that consisted of the pusher plate, blood sac and pump case. A quasi-static analysis was used to allow for nonlinearities due to contact and material deformation. The 3D FE model showed that blood sac stresses are not adversely affected by the location of the inlet and outlet ports of the device and that over the systolic ejection phase of the simulation the prediction of blood sac stresses from the full 3D model and an axisymmetric model are the same. Minimizing stresses in the blood sac will increase the longevity of the blood sac in vivo.
Medical Engineering & Physics 02/2009; 31(4):454-60. · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While much work has previously been done in the modeling of skeletal muscle, no model has, to date, been developed that describes the mechanical behavior with an explicit strain-energy function associated with the active response of skeletal muscle tissue. A model is presented herein that has been developed to accommodate this design consideration using a robust dynamical approach. The model shows excellent agreement with a previously published model of both the active and passive length-tension properties of skeletal muscle.
Journal of Biomechanical Engineering 01/2009; 130(6):061017. · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Partial meniscectomy is known to cause osteoarthritis (OA) of the underlying cartilage as well as alter the load on the remaining meniscus. Removal of 30-60% of the medial meniscus increases compressive strains from a maximum of approximately 10% to almost 20%. The goal of this study is to determine if meniscal cells produce catabolic molecules in response to the altered loading that results from a partial meniscectomy.
Relative changes in gene expression of interleukin-1 (IL-1), inducible nitric oxide synthase (iNOS) and subsequent changes in the concentration of nitric oxide (NO) released by meniscal tissue in response to compression were measured. Porcine meniscal explants were dynamically compressed for 2 h at 1 Hz to simulate physiological stimulation at either 10% strain or 0.05 MPa stress. Additional explants were pathologically stimulated to either 0% strain, 20% strain or, 0.1 MPa stress.
iNOS and IL-1 gene expression and NO release into the surrounding media were increased at 20% compressive strain compared to other conditions. Pathological unloading (0% compressive strain) of meniscal explants did not significantly change expression of IL-1 or iNOS genes, but did result in an increased amount of NO released compared to physiological strain of 10%.
These data suggest that meniscectomies which reduce the surface area of the meniscus by 30-60% will increase the catabolic activity of the meniscus which may contribute to the progression of OA.
Osteoarthritis and Cartilage 05/2008; 16(10):1213-9. · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The main functions of the human musculoskeletal system are to sustain loads and provide mobility. Bones and joints themselves cannot produce movement; skeletal muscles provide the ability to move. Knowledge of muscle forces during given activities can provide insight into muscle mechanics, muscle physiology, musculoskeletal mechanics, neurophysiology, and motor control. However, clinical examinations or instrumented strength testing only provides information regarding muscle groups. Musculoskeletal models are typically needed to calculate individual muscle forces.
[Show abstract][Hide abstract] ABSTRACT: In a healthy meniscus, the compressive strains are approximately 2–10%.  When 30% or more of the tissue is removed during partial meniscectomy, strains increase to approximately 18%.  We have previously shown that dynamic compressive strains of 20% to meniscal explants results in an increase in proteoglycan (PG) breakdown, nitric oxide (NO) production, metalloproteinases 1, 3, and 13 (MMP-1, MMP-3, and MMP-13) compared to 0, 5, and 10% compressive strain. [2,3,4] The objective of this study was to determine if interruption of the IL-1 pathway would alter this biochemical response to dynamic mechanical compression.
[Show abstract][Hide abstract] ABSTRACT: Motivated by our interest in examining meniscal mechanotransduction processes, we report on the validation of a new tissue engineering bioreactor. This paper describes the design and performance capabilities of a tissue engineering bioreactor for cyclic compression of meniscal explants. We showed that the system maintains a tissue culture environment equivalent to that provided by conventional incubators and that its strain output was uniform and reproducible. The system incorporates a linear actuator and load cell aligned together in a frame that is contained within an incubator and allows for large loads and small displacements. A plunger with six Teflon-filled Delrin compression rods is attached to the actuator compressing up to six tissue explants simultaneously and with even pressure. The bioreactor system was used to study proteoglycan (PG) breakdown in porcine meniscal explants following various input loading tests (0-20% strain, 0-0.1 MPa). The greatest PG breakdown was measured following 20% compressive strain. These strain and stress levels have been shown to correspond to partial meniscectomy. Thus, these data suggest that removing 30-60% of meniscal tissue will result in the breakdown of meniscal tissue proteoglycans.
Annals of Biomedical Engineering 12/2006; 34(11):1758-66. · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Procedures used by tissue banks in selecting meniscal allografts that will best restore normal contact pressure at the time of surgical implantation into a recipient's knee should be improved. Our objective was to develop regression equations that use dimensions measured from magnetic resonance (MR) images of the contralateral knee to predict values of important meniscal parameters of the injured knee. Another objective was to incorporate these equations into an algorithm for selecting allografts that best match the size and shape of the damaged meniscus (either medial or lateral). In each of 10 knee specimens, four transverse and six cross-sectional parameters of the medial and lateral menisci were quantified from measurements obtained using a laser-based, noncontacting, 3-D coordinate digitizing system. In each of 10 contralateral knee specimens, six transverse and 24 cross-sectional (i.e., perpendicular to transverse plane) dimensions were measured for the medial and lateral menisci from MR images of each knee specimen. Simple linear regression equations related these 10 parameters to each of 38 predictor variables determined from magnetic resonance imaging (MRI) dimensions and the best regression equation for each parameter was identified. Requiring only 9 of the 30 dimensions as predictor variables, the best regression equations predicted 8 of 10 and 10 of 10 medial and lateral menisci parameters, respectively, with R2 values>0.500. The algorithm for selecting meniscal allografts involves: collecting an inventory of meniscal allografts and determining the 10 meniscus parameter values for all allografts in the inventory; measuring the dimensions as required from MRI scans of the uninjured knee; using the dimensions as inputs to the regression equations to predict values of meniscal parameters; and selecting the meniscal allograft from the inventory that best matches the predicted values of meniscal parameters. Selecting meniscal allografts using our new algorithm may enable allografts to better meet the clinical objectives of meniscal transplantation, which are to reduce pain in some patients following meniscal resection and to inhibit the degeneration of the articular cartilage.
Journal of Orthopaedic Research 07/2006; 24(7):1535-43. · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 [Chen, M.I., Branch, T.P., et al., 1996. Is it important to secure the horns during lateral meniscal transplantation? A cadaveric study. Arthroscopy 12(2), 174-181; Alhalki, M.M., et al., 1999. How three methods for fixing a medial meniscal autograft affect tibial contact mechanics. American Journal of Sports Medicine 27(3), 320-328; Haut Donahue, T.L., et al., 2003. How the stiffness of meniscal attachments and meniscal material properties affect tibio-femoral contact pressure computed using a validated finite element model of the human knee joint. Journal of Biomechanics 36(1), 19-34]. The complex loading environment in the knee lends itself to different loading environments for each meniscal attachment. We hypothesize that the creep and stress relaxation characteristics of the horn attachments will be different for the anterior versus posterior, and medial versus lateral attachments. To test this hypothesis, the stress relaxation and creep characteristics of the meniscal horn attachments were determined. The stress relaxation properties of load/stress at the end of the test, and the load/stress relaxation rate demonstrated no significant statistical differences between the attachments. Unlike the stress relaxation properties, the creep properties demonstrated some significant differences amongst the attachments. The normalized displacement at the end of the test, normalized creep rate and strain creep rate for the lateral anterior attachment were significantly different than those of the medial posterior attachment (p<0.05). The two anterior attachments had significantly different strains at the end of the test, as well as significantly different creep strain rates (p<0.05). The two attachments of the medial meniscus revealed no significant differences between any of the creep properties measured (p>0.05). The time dependent properties obtained in this experiment provide insight into the behavior of meniscal horn attachments under various loading situations. The results indicate that a suitable meniscal replacement may require different properties for the lateral and medial horns.
Journal of Biomechanics 01/2006; 39(16):3055-61. · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mechanical environment of the skeleton plays an important role in the establishment and maintenance of structurally competent bone. Biophysical signals induced by mechanical loading elicit a variety of cellular responses in bone cells, however, little is known about the underlying mechanotransduction mechanism. We hypothesized that bone cells detect and transduce biophysical signals into biological responses via a mechanism requiring annexin V (AnxV). AnxV, a calcium-dependent phospholipid binding protein, has several attributes, which suggest it is ideally suited for a role as a mechanosensor, possibly a mechanosensitive ion channel. These include the ability to function as a Ca2+ selective ion channel, and the ability to interact with both extracellular matrix proteins and cytoskeletal elements. To test the hypothesis that AnxV has a role in mechanosensing, we studied the response of osteoblastic cells to oscillating fluid flow, a physiologically relevant physical signal in bone, in the presence and absence of AnxV inhibitors. In addition, we investigated the effects of oscillating flow on the cellular location of AnxV. Oscillating fluid flow increased both [Ca2+]i levels and c-fos protein levels in osteoblasts. Disruption of AnxV with blocking antibodies or a pharmacological inhibitor, K201 (JTV-519), significantly inhibited both responses. Additionally, our data show that the cellular location of AnxV was modulated by oscillating fluid flow. Exposure to oscillating fluid flow resulted in a significant increase in AnxV at both the cell and nuclear membranes. In summary, our data suggest that AnxV mediates flow-induced Ca2+ signaling in osteoblastic cells. These data support the idea of AnxV as a Ca2+ channel, or a component of the signaling pathway, in the mechanism by which mechanical signals are transduced into cellular responses in the osteoblast. Furthermore, the presence of a highly mobile pool of AnxV may provide cells with a powerful mechanism by which cellular responses to mechanical loading might be amplified and regulated.
[Show abstract][Hide abstract] ABSTRACT: Fluid flow has been shown to be a potent physical stimulus in the regulation of bone cell metabolism. In addition to membrane shear stress, loading-induced fluid flow will enhance chemotransport due to convection or mass transport thereby affecting the biochemical environment surrounding the cell. This study investigated the role of oscillating fluid flow induced shear stress and chemotransport in cellular mechanotransduction mechanisms in bone. Intracellular calcium mobilization and prostaglandin E(2) (PGE(2)) production were studied with varying levels of shear stress and chemotransport. In this study MC3T3-E1 cells responded to oscillating fluid flow with both an increase in intracellular calcium concentration ([Ca(2+)](i)) and an increase in PGE(2) production. These fluid flow induced responses were modulated by chemotransport. The percentage of cells responding with an [Ca(2+)](i) oscillation increased with increasing flow rate, as did the production of PGE(2). In addition, depriving the cells of nutrients during fluid flow resulted in an inhibition of both [Ca(2+)](i) mobilization and PGE(2) production. These data suggest that depriving the cells of a yet to be determined biochemical factor in media affects the responsiveness of bone cells even at a constant peak shear stress. Chemotransport alone will not elicit a response, but it appears that sufficient nutrient supply or waste removal is needed for the response to oscillating fluid flow induced shear stress.
Journal of Biomechanics 10/2003; 36(9):1363-71. · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Due to ready availability, decreased cost, and freedom from transmissible diseases in humans such as hepatitis and AIDS, it would be advantageous to use tendon grafts from farm animals as a substitute for human tendon grafts in in vitro experiments aimed at improving the outcome of anterior cruciate ligament (ACL) reconstructive surgery. Thus the objective of this study was to determine whether an anterior cruciate ligament (ACL) graft composed of two loops of bovine common digital extensor tendon has the same viscoelastic, structural, and material properties as a graft composed of a double loop of semitendinosus and gracilis tendons from humans. To satisfy this objective, grafts were constructed from each tissue source. The cross-sectional area was measured using an area micrometer, and each graft was then pulled using a materials testing system while submerged in a saline bath. Using two groups of tendon grafts (n = 10), viscoelastic tests were conducted over a three-day period during which a constant displacement load relaxation test was followed by a constant amplitude, cyclic load creep test (first day), a constant load creep test (second day), and an incremental cyclic load creep test (third day). Load-to-failure tests were performed on two different groups of grafts (n = 8). When the viscoelastic behavior was compared, there were no significant differences in the rate of load decay or the final load (relaxation test) and rates of displacement increase or final displacements (creep tests) (p > 0.115). To compare both the structural and material properties in the toe region (i.e., < 250 N) of the load-elongation curve, the tangent stiffness and modulus functions were computed from parameters used in an exponential model fit to the load (stress)-elongation (strain) data. Although one of the two parameters in the functions was different statistically, this difference translated into a difference of only 0.03 mm in displacement at 250 N of load. In the linear region (i.e., 50-75 percent of ultimate load) of the load-elongation curve, the linear stiffness of the two graft types compared closely (444 N/mm for bovine and 418 N/mm for human) (p = 0.341). At failure, the ultimate loads (2901 N and 2914 N for bovine and human, respectively) and the ultimate stresses (71.8 MPa and 65.6 MPa for bovine and human, respectively) were not significantly different (p > 0.261). The theoretical effect of any differences in properties between these two grafts on the results of two types of in vitro experiments (i.e., effect of surgical variables on knee laxity and structural properties of fixation devices) are discussed. Despite some statistical differences in the properties evaluated, these differences do not translate into important effects on the dependent variables of interest in the experiments. Thus the bovine tendon graft can be substituted for the human tendon graft in both types of experiments.
Journal of Biomechanical Engineering 04/2001; 123(2):162-9. · 1.52 Impact Factor