Antioxidants block cyclic loading induced chondrocyte death.

Articular cartilage in congruous joints benefits from the moderate stresses and strains associated with normal cyclic loading. However, loading of joints with surface incongruities can lead to local stress and strain elevation at "step-off' sites where cartilage is not fully buttressed b ysurrounding matrix. Excessive stresses and strains predicted to occur at such sites may induce apoptosis, a process thought to promote cartilage degeneration and osteoarthritis (OA) through chondrocyte attrition. We hypothesized that the induction of apoptosis is mediated by oxidants, and that antioxidants can reduce elevated stress-induced chondrocyte attrition. To test this we exposed cylindrical cartilage explants from human articular cartilage to radially unconfined cyclic axial compression (3600 cycles, 1 Hz, 50% duty cycle) using two different physiologic loads (2MPa and 5 MPa). We found that 30% of chondrocytes in the superficial zone died within 24 hours of exposure to loading with 5 MPa axial compression, whereas mortality was limited to less than 15% with 2 MPa axial compression. Similarly, lactate accumulation in the medium was suppressed by compression with 5 MPa, but not 2 MPa. Approximately 80% of cell death induced by 5 MPa compression was blocked by pre-incubation of the explants in a variety of anti-oxidants including vitamin E, n-acetyl cysteine (NAC), and a superoxide dismutase mimetic (SOD). SOD and NAC also prevented the suppression of lactate secretion after 5 MPa compression. These observations support the hypothesis that the harmful effects of abnormal cyclic loading are mediated by oxidants and suggest that treatments to prevent OA may include methods of minimizing oxidative damage to chondrocytes.

Effects of mechanical testing device variables on polymer composite femoral stem strains.

Polymer composite femoral stems do not have a well-established in vitro mechanical testing method. The objective of this study was to examine mechanical testing devices for pressfit composite stems, using finite element analysis. The goals were to examine the effects of testing device design variables (geometry, material, interface friction, embedding height and applied load angle) and to reproduce the maximum strains of the stem implanted in a femur. The stem strains were affected by design changes to the testing device. The maximum normal and interlaminar shear strains of the composite stem in the femur were not as well reproduced by the testing device as were the maximum in-plane tensile strains. Decreasing the embedding height increased the stem strains and shifted the stem failure location from the neck to the embedding height. Testing a femoral stem using a testing device with a low embedding height may be inappropriate when trying to induce neck failure, since failure may occur at the embedding height instead of in the neck. A single-material testing device of birchwood, an orthotropic material with a longitudinal stiffness in the range of bone; best simulated a femur in this study.

Structural properties of a new design of composite replicate femurs and tibias.

The purpose of this study was to compare the structural properties of a new vs. established design of composite replicate femurs and tibias. The new design has a cortical bone analog consisting of short-glass-fiber-reinforced (SGFR) epoxy, rather than the fiberglass-fabric-reinforced (FFR) epoxy in the currently available design. The hypothesis was that this new cortical bone analog would improve the uniformity of structural properties between specimens, while having mean stiffness values in the range of natural human bones. The composite replicate bones were tested under bending, axial, and torsional loads. In general, the new SGFR bones were significantly less stiff than the FFR bones, although both bone designs reasonably approximated the structural stiffnesses of natural human bones. With the exceptions of the FFR bone axial tests, the highest variability between specimens was 6.1%. The new SGFR bones had similar variability in structural properties when compared to the FFR bones under bending and torsional loading, but had significantly less variability under axial loading. Differences in epiphyseal geometry between the FFR and SGFR bones, and subsequent seating in the testing fixtures, may account for some of the differences in structural properties; axial stiffness was especially dependent on bone alignment. Stiffness variabilities for the composite replicate bones were much smaller than those seen with natural human bones. Axial strain distribution along the proximal-medial SGFR femur had a similar shape to what was observed on natural human femurs by other investigators, but was considerably less stiff in the more proximal locations.

A physical model for simulating fusion of impaction-grafted morselized cancellous bone.

This article describes a method to simulate fusion of morselized cancellous bone. The morselized cancellous bone is mixed with an epoxy adhesive, in empirically determined proportions. The mixture is then impacted into a construct. When the epoxy cures, the morselized material fuses into a cohesive, contiguous structure with a compressive modulus equivalent to that of intact cancellous bone. This model can be used to study biomechanical aspects of fused impaction grafts.

Cartilage responses to a novel triaxial mechanostimulatory culture system.

We have developed a novel mechanically active cartilage culture device capable of modulating the interplay between compression and shear, at physiologic stress levels (2-5 MPa). This triaxial compression culture system subjects cylindrical cartilage explants to pulsatile axial compression from platen contact, plus pulsatile radially transverse compression from external fluid compression. These compressive loads can be independently modulated to impose stress states that resemble normal physiologic loading, and to investigate perturbations of individual components of the multi-axial stress state, such as increased shear stress. Based on the observation that joint incongruity predisposes cartilage to premature degeneration, we hypothesized that cartilage extracellular matrix (ECM) synthesis would be inhibited under conditions of low transverse buttressing (high shear stress). To test this hypothesis, we compared ECM synthesis in human cartilage explants exposed to axial compression without transverse compression (high shear stress), versus explants exposed to axial compression plus an equal level of transverse compression (low shear stress). Both total (35)SO(4) incorporation and aggrecan-specific (35)SO(4) incorporation were significantly inhibited by axial compression, relative to axial plus transverse compression.

High density polyetherurethane foam as a fragmentation and radiographic surrogate for cortical bone.

BACKGROUND: Although one of the most important factors in predicting outcome of articular fracture, the comminution of the fracture is only subjectively assessed. To facilitate development of objective, quantitative measures of comminution phenomena, there is need for a bone fragmentation surrogate. METHODS: Laboratory investigation was undertaken to develop and characterize a novel synthetic material capable of emulating the fragmentation and radiographic behavior of human cortical bone. RESULT: Screening tests performed with a drop tower apparatus identified high-density polyetherurethane foam as having suitable fragmentation properties. The material's impact behavior and its quasi-static mechanical properties are here described. Dispersal of barium sulfate (BaSO4) in the resin achieved radio-density closely resembling that of bone, without detectably altering mechanical behavior. The surrogate material's ultimate strength, elastic modulus, and quasi-static toughness are within an order of magnitude of those of mammalian cortical bone. The spectrum of comminution patterns produced by this material when impacted with varying amounts of energy is very comparable to the spectrum of bone fragment comminution seen clinically. CONCLUSIONS: A novel high-density polyetherurethane foam, when subjected to impact loading, sustains comminuted fracture in a manner strikingly similar to cortical bone. Moreover, since the material also can be doped with radio-opacifier so as to closely emulate bone's radiographic signature, it opens many new possibilities for CT-based systematic study of comminution phenomena.

Assessing the accuracy of a prototype drill guide for fibular graft placement in femoral head necrosis.

A prototype drill guide was developed to improve the accuracy of surgical placement of fibular grafts for the treatment of femoral head necrosis. To document performance, two tantalum beads, one placed on the lateral femoral shaft and the other embedded in the superior portion of the head, were used to define the desired graft tract in a series of seven surrogate femurs. Two orthogonal x-rays of the drill guide mounted on each surrogate femur were taken both before and after drilling. After stylus digitization of each x-ray pair, a computer program calculated the achieved accuracy of the drill. The mean of the absolute error between the desired versus obtained position of the drill tip was 3.68 mm (s.d. 1.24 mm), and the random component of the error was 1.98 mm (s.d. 0.89 mm).

Frictional insertion kinetics of bone biopsy needles.

Patients undergoing a percutaneous bone biopsy often complain of pain during needle insertion, despite local anesthesia. Bone biopsy needles are typically inserted with combined axial and twisting motions. These motions could cause pain through frictional heating or direct mechanical irritation. The hypothesis of this study is that the insertion energy of bone biopsy needles can be reduced by modifying the insertion kinetics or by adding a friction-lowering coating to the needles. Jamshidi bone biopsy needles were driven into a bone analog model by an MTS materials testing machine operating under axial and rotational displacement control. The load/torque recordings showed that, to significantly decrease insertion energy and peak resistance to needle insertion, axial velocity and angular frequency had to be decreased to one quarter of the baseline, typical-usage parameters. However the increased insertion time may not be acceptable clinically. The majority of the insertion energy was associated with the needle axial thrust rather than with needle twisting. Overcoming friction against the side of the needle consumed much more of the insertion energy than did the process of cutting per se. None of five needle coatings tested succeeded in appreciably lowering the insertion energy, and none achieved a substantial decrease in peak resisting force.

Leuprolide acetate affects intestinal motility in female rats before and after ovariectomy.

Leuprolide acetate, a gonadotropin-releasing hormone (GnRH) analogue, is currently being proposed to control debilitating symptoms in women with functional bowel disease. Whether leuprolide alters gastrointestinal motility as part of its actions is unknown. This study was designed to assess, using myoelectric techniques in an animal model, the effects of leuprolide on potential mechanisms of neuromuscular function of small intestine. Female rats with (n = 6) or without (n = 8) bilateral ovariectomy were used to study jejunal motility before and after leuprolide therapy. Throughout the study, daily leuprolide dosages of 0.02, 0.2, or 0.4 micrograms/kg were injected into intact rats and 0.02, 0.2, 0.4, 1.0, or 2.5 micrograms/kg into ovariectomized rats. Recordings were made while the rats were fasted and postprandial and before and after leuprolide administration. Under control conditions, migrating myoelectric complexes (MMCs) were found in intact female rats, whether fasted or postprandial. After ovariectomy, postprandial controls and those treated with low-dose leuprolide (0.02, 0.2, and 0.4 micrograms) had typical fed-state patterns and no MMCs, but at 1.0 and 2.5 micrograms the fed state was inhibited and cycling MMCs occurred at a frequency similar to that of fasted controls. Reproductive hormones thus have a significant effect on gastrointestinal motility.