T.L. Haut Donahue

Mechanosensitivity of bone cells to oscillating fluid flow induced shear stress may be modulated by chemotransport.

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.

Constitutive Modeling of Skeletal Muscle Tissue with an Explicit Strain-Energy Function

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.

Nanoindentation of the insertional zones of human meniscal attachments into underlying bone

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.

Meniscal tissue explants response depends on level of dynamic compressive strain

OBJECTIVE 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. METHOD 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. RESULTS 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. CONCLUSION 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.

Time dependent properties of bovine meniscal attachments: Stress relaxation and creep

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.

IL-1 and INOS gene expression and NO synthesis in the superior region of meniscal explants are dependent on the magnitude of compressive strains

OBJECTIVE 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. METHOD 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. RESULTS 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%. CONCLUSION 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.

Finite element analysis of stresses developed in the blood sac of a left ventricular assist device

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.

Constitutive Modeling of Skeletal Muscle Tissue

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.© 2007 ASME

Traumatic Anterior Cruciate Ligament Tear and Its Implications on Meniscal Degradation: A Preliminary Novel Lapine Osteoarthritis Model

The meniscus plays a crucial role in the dynamics of the knee. Damage to the meniscus can influence proprioception, stability, and mobility of the knee [1]. Risk factors of meniscal tears include prolonged or repeated deep knee bending, obesity, and sporting injuries [2]. Acute injury, as seen in alpine sports, involves complex dynamics which can damage singular or multiple tissue structures of the knee [2]. It is not uncommon for meniscal injuries to occur in conjunction with ACL lesions, and the loading imbalance that results in ACL lesions may also initiate meniscal tears [3, 4]. Investigations of meniscal tears following ACL rupture have indicated chronic damage to medial menisci more so than lateral menisci [5]. However, experimental studies of acute damage following ACL transection are not consistent, with some showing more lateral damage acutely and some showing equality between medial and lateral meniscal damage [5].Copyright

Regional Glycosaminoglycan Coverage of Healthy Rabbit Menisci

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 [1]. 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.© 2009 ASME