Using 'subcement' to simulate the long-term fatigue response of cemented femoral stems in a cadaver model: could a novel preclinical screening test have caught the Exeter matt problem?

Previously, cement was formulated with degraded fatigue properties (subcement) to simulate long-term fatigue in short-term cadaver tests. The present study determined the efficacy of subcement in a 'preclinical' test of a design change with known clinical consequences: the 'polished'-to-'matt' transition of the Exeter stem (revision rates for polished stems were twice those for matt stems). Contemporary stems were bead blasted to give Ra = 1 microm (matt finish). Matt and polished stems were compared in cadaver pairs under stair-climbing loads (three pairs of size 1; three pairs of size 3). Stem micromotion was monitored during loading. Post-test transverse sections were examined for cement damage. Cyclic retroversion decreased for polished stems but increased for matt stems (p < 0.0001). The implant size had a substantial effect; retroversion of (larger) size-3 stems was half that of size-1 stems, and polished size-3 stems subsided 2.5 times more than the others. Cement damage measures were similar and open through-cracks occurred around both stems of two pairs. Stem retroversion within the mantle resulted in stem-cement gaps of 50-150 microm. Combining information on cyclic motion, cracks, and gaps, it was concluded that this test 'predicted' higher revision rates for matt stems (it also implied that polished size-3 stems might be superior to size-1 stems).

Vacuum-mixing cement does not decrease overall porosity in cemented femoral stems: an in vitro laboratory investigation.

The role of vacuum mixing on the reduction of porosity and on the clinical performance of cemented total hip replacements remains uncertain. We have used paired femoral constructs prepared with either hand-mixed or vacuum-mixed cement in a cadaver model which simulated intra-operative conditions during cementing of the femoral component. After the cement had cured, the distribution of its porosity was determined, as was the strength of the cement-stem and cement-bone interfaces. The overall fraction of the pore area was similar for both hand-mixed and vacuum-mixed cement (hand 6%; vacuum 5.7%; paired t-test, p = 0.187). The linear pore fractions at the interfaces were also similar for the two techniques. The pore number-density was much higher for the hand-mixed cement (paired t-test, p = 0.0013). The strength of the cement-stem interface was greater with the hand-mixed cement (paired t-test, p = 0.0005), while the strength of the cement-bone interface was not affected by the conditions of mixing (paired t-test, p = 0.275). The reduction in porosity with vacuum mixing did not affect the porosity of the mantle, but the distribution of the porosity can be affected by the technique of mixing used.

Nonaffinity purification of recombinant gp120 for use in AIDS vaccine development.

The gene encoding the major envelope glycoprotein of the HIV-SF2 isolate was engineered for the secretion of recombinant gp120 (rgp120SF2) from permanent Chinese hamster ovary (CHO) cell lines. Cellular production methods were scaled up and a method for purification of the secreted glycoprotein was devised. Mild purification conditions were selected in order to preserve the native structure of the protein. rgp120SF2 exhibits a molecular weight of 120 kDa in reduced or nonreduced SDS gels; thus the polypeptide chain is intact. Deglycosylated rgp120SF2 has the predicted molecular weight of the polypeptide backbone, 54 kDa. Gel-filtration HPLC in a nondenaturing buffer at neutral pH yields a molecular weight estimate of approximately 120 kDa. Purified rgp120 closely resembles authentic viral gp120 by several physical, chemical, and immunochemical tests. rgp120SF2 reacts strongly with human HIV-positive sera, monoclonal antibodies reactive with HIV-SF2 and HIV-MN viral envelope, and a human virus-neutralizing monoclonal antibody that maps to a conserved discontinuous epitope on HIV-1 gp120. Purified rgp120SF2 forms a 1:1 molecular complex with soluble recombinant human CD4 (rCD4) receptor, as demonstrated by gel-filtration HPLC; binding is high affinity (Kd approximately 2 x 10(-9) M).

Functional and immunological characterization of SIV envelope glycoprotein produced in genetically engineered mammalian cells.

Retroviral envelope glycoproteins interact with cell receptors and are targets for antiviral immune responses in infected hosts. Macaque simian immunodeficiency virus (SIVmac) is a T-lymphocytopathic lentivirus which causes an AIDS-like disease in rhesus macaques. The envelope gene of SIVmac encodes a precursor glycoprotein (gp160) which is cleaved into an external domain (gp130) and a transmembrane domain (gp32). To investigate the functional and immunological properties of the SIV external envelope glycoprotein, we have used genetically engineered mammalian cells to produce recombinant gp130 (rgp130). The rgp130 has the appropriate molecular weight, is glycosylated, and has native conformation as determined by binding to the cell receptor for SIV, the CD4 antigen. Rhesus macaques immunized with purified rgp130 formulated in muramyl dipeptide adjuvant generated high titers of antienvelope antibodies. Antibodies from these macaques were tested for in vitro virus neutralization; very low or undetectable levels of neutralization were observed. In contrast, neutralizing antibodies were readily detected in sera from goats immunized with rgp130. With respect to cell-mediated immunity, proliferative responses to rgp130 were demonstrated in peripheral blood monocyte cells (PBMC) from macaques immunized with the recombinant glycoprotein as well as in PBMC from SIV-infected animals. These results show that rgp130 is functional and immunogenic; the potential of rgp130 for protective immunization remains to be determined.

Mixed-mode fracture toughness of the cobalt-chromium alloy/polymethylmethacrylate cement interface.

Mechanical debonding of the stem/cement interface has been implicated in the failure process of cemented femoral hip components. The nature of this failure process remains poorly understood due, in part, to limited understanding of how interfacial debonding occurs in response to a wide range of loading conditions. The purpose of this investigation was to determine the fracture toughness of the cobalt-chromium alloy/polymethylmethacrylate interface under mixed-mode loading conditions. The hypothesis was that the critical energy release rate was dependent on the phase angle of the crack tip and that the fracture response would be significantly different for a smooth compared with rough interface surface. A novel in-plane shear test fixture was developed with use of a combination of finite element and experimental fracture-mechanics tests. A wide range (-65-60 degrees) of phase angles was determined with the in-plane shear test and a clamped cantilever-beam test. Sixty experimental tests were performed for cobalt-chromium alloy bars with a plasma-sprayed coating or a precoat of polymethylmethacrylate over a satin-finished surface. For the specimens with the plasma-sprayed coating, critical energy release rates (500-700 J/m2) were not a function of the phase angle of the crack tip. In contrast, critical energy release rates (15-80 J/m2) were found to be strongly affected by the phase angle for the specimens precoated with polymethylmethacrylate. The critical energy release rate for specimens with the plasma-sprayed surface was significantly (p < 0.01) greater than for those precoated with polymethylmethacrylate. The critical energy release rate increased markedly with the phase angle of the crack tip for the specimens precoated with polymethylmethacrylate. The results suggest that the failure response of a stem with a plasma-sprayed surface may be insensitive to the loading angle of the crack tip, whereas a stem precoated with polymethylmethacrylate may be more likely to debond under tensile opening loading.

Influence of stem geometry on mechanics of cemented femoral hip components with a proximal bond.

Nonlinear, three-dimensional, finite element models of cemented femoral hip components with a proximal stem-cement bond were developed with use of a Charnley stem geometry and a modified Charnley stem geometry that had a cylindrical cross section over the distal two-thirds of the stem (Distal-Round). Peak tensile stresses in the proximal cement mantle increased 63 and 74% for the Charnley and Distal-Round stems, respectively, when the proximal stem-cement interface was debonded. The shear stresses over the stem-cement interface with a proximal bond were 29% larger for the Distal-Round stem than for the Charnley stem. After the proximal stem-cement interface was debonded, the peak tensile stresses in the cement mantle were 15% larger for the Distal-Round stem than for the Charnley stem. The results illustrate that stresses within the proximal cement mantle could be substantially reduced for both Charnley and Distal-Round stems through use of a proximal stem-cement bond. However, the risk of debonding may be higher for the Distal-Round stem because of increased shear stresses, and once debonded the risk of further loosening due to failure of the cement mantle would also be higher for the Distal-Round stem.

Effects of stem length on mechanics of the femoral hip component after cemented revision.

Bone loss in the proximal femur at the time of revision hip arthroplasty for a failed primary cemented femoral component can substantially reduce the stability of the revision stem. Use of an extended-length femoral component has been suggested to aid in achieving long-term fixation; however, the optimal stem length is unknown. A three-dimensional finite element model of a Charnley-type revision femoral component in a sclerotic shell of cortical bone devoid of cancellous bone was developed, and five different stem lengths ranging from 140 to 273 mm were used. The interface between the sclerotic bone and cement mantle consisted of fibrous tissue. Distal to the sclerotic bone, bonding was allowed between the cement and bone. Relative motion between the cement and bone was reduced substantially when the stem extended beyond the original defect. Maximum principal stresses in the proximal cement mantle decreased from 7.7 to 5.5 MPa, but cement stresses near the distal tip increased from 7.9 to 10.7 MPa when the stem just bridged the defect. Further increases in stem length reduced the distal cement stresses. Increases beyond two femoral diameters had a minor effect on changes in relative motion, cement mantle stresses, and stresses across the cement-bone interface. The results suggest that a femoral component that extends beyond the area of cancellous bone defect by two femoral diameters will be most effective in minimizing stresses and motion that could be associated with clinical loosening of the cemented revision. A shorter stem that just bridges the cancellous bone defect left from the primary procedure may not provide adequate distal fixation due to high cement-bone shear stresses.

Pre-yield and post-yield shear behavior of the cement-bone interface.

Aseptic loosening of cemented total hip replacements is thought to involve mechanical failure of the cement-bone interface. However, the mechanical response of the interface, particularly the post-yield behavior, is not well understood. The purpose of this study was to determine the constitutive behavior of the cement-bone interface for loading in shear using a combination of experimental and finite element methods. A total of 55 cement-bone specimens (5 x 10 x 15-20 mm) from the proximal femur of human cadavers were loaded to failure under displacement control with use of a custom shear test jig. Finite element models of the test specimens were made and included provision for a two-parameter nonlinear interface model at the cement-bone interface. The experimental tests revealed a complicated load versus displacement response with an initial linear region and a reduction in slope until the ultimate strength (2.25+/-1.49 MPa) was reached, followed by an exponential decrease in load with increasing displacement until the entire interface debonded. Failure most often occurred at the cement-bone interface, where the cement penetrated into the bone with bone remaining in the cement in 30 specimens and with bone remaining in the cement and cement spicules remaining in the bone in 22 specimens. The adjacent bulk bone and cement did not appear to be permanently deformed. Finite element models of the test specimens revealed that failure initiated at the base of the test specimen before the peak load had been reached. The two interface parameters, interface strength (2.71+/-1.90 MPa) and interface-softening exponent (4.96+/-3.47 1/mm), could be determined directly from the experimental data and provided a good fit with the experimental structural response for a wide range of interface strengths. These results show that the cement-bone interface does not fail abruptly when the shear strength is reached but absorbs a substantial amount of energy with post-yield strain-softening behavior.

Frequency spectrum analysis of wrist motion for activities of daily living.

A frequency spectral analysis was performed on wrist motion data for 24 activities of daily living (ADLs). Wrist motion was measured using a triaxial electrogoniometer attached to the wrist using tape (for 12 subjects) and pins (for one subject). Results show that the average predominant frequency component of these ADLs was approximately 1 Hz with 75% of the spectral energy less than 5 Hz. The taped-on electrogoniometer, when compared with the pinned electrogoniometer, was adequate for calculating the predominant frequency component and spread of spectral data, but overestimated the magnitudes of the maximum spectral density and total area of the spectral curves. This discrepancy was largest for axial rotation.

Mechanical characteristics of the stem-cement interface.

The mechanical characteristics of the interface between a metallic stem and the surrounding poly(methyl methacrylate) bone cement were determined from experimental tests and finite element analyses. Push-through-stem tests of straight and tapered titanium alloy stems, surrounded by cement columns, were performed and the resulting load-displacement behavior and strain distribution on the surface of the cement column were measured for loading, unloading, and reloading. Test geometries were modelled using nonlinear, axisymmetric, finite element analyses, which incorporated Coulomb friction elements at the titanium alloy-cement interface. Initial residual stresses, due to curing of the cement column, were modeled by thermal contraction of the cement. Good agreement was obtained between load-displacement curves and surface strains predicted from the nonlinear analysis and those obtained from experiments, when a coefficient of friction of 0.3 was assumed for the stem-cement interface. These results show that, in the absence of chemical adhesion, the load-displacement behavior of a stem-cement composite can be described completely in terms of the friction at the interface and the residual stresses normal to the interface.

Mixed-mode failure response of the cement-bone interface.

Mechanical failure of the cement-bone interface can contribute to clinical loosening of cemented total hip replacements. The conditions that cause loosening are poorly understood, in part, due to a lack of information on the mechanical behavior of the cement bone interface. The purpose of this study was to determine the mechanical behavior of the cement-bone interface due to mixed-mode (combined tension and shear) loading and to develop a failure model for the cement bone interface. Laboratory tests of machined cement-bone test specimens were performed with mixed-mode loading conditions (loading angles of 22.5 degrees, 45 degrees, and 67.5 degrees) to determine the mechanical response in the pre-yield and post-yield state. After accounting for the quantity of interdigitated bone as a covariate, the mixed-mode data were combined with previous tension (0 degrees) and shear data (90 degrees) to develop a failure model for the cement bone interface. The strength of the interface was positively correlated with the quantity of interdigitated bone (r2 = 0.70, 0.53, 0.49, for 22.5 degrees, 45 degrees, and 67.5 degrees, respectively). There was a significant increase in failure strength (P < 0.001) with increasing mixed-mode angle. When all data were incorporated into an elliptical failure criterion, the average error between the actual and predicted strength was 33%. These results can now be incorporated into constitutive models of the cement bone interface to determine the initiation and progression of interface failure in cemented total hip replacements.

Prevention of mesh-dependent damage growth in finite element simulations of crack formation in acrylic bone cement.

Peak stress levels predicted in finite element analysis (FEA) usually depend on mesh density, due to singular points in the model. In an earlier study, an FEA algorithm was developed to simulate the damage accumulation process in the cement mantle around total hip replacement (THR) implants. It allows cement crack formation to be predicted, as a function of the local cement stress levels. As the simulation is driven by mesh-dependent peak stresses, predicted crack formation rates are also likely to be mesh dependent. The aim of this study was to evaluate the mesh dependence of the predicted crack formation process, and to present a method to reduce the mesh dependence. Crack-propagation experiments were simulated. Experimental specimens, representing transverse slices of cemented THR reconstructions, were subjected to cyclic torsional loading. Crack development around the corners of the stem was monitored. The experiments were simulated using three meshes with increasing levels of mesh refinement. Crack locations and orientations were accurately predicted, and were virtually independent of the level of mesh refinement. However, the experimental crack propagation rates were overestimated considerably, increasing with mesh refinement. To eliminate the effect of stress singularities around the corners of the stem, a stress averaging algorithm was applied in the simulation. This algorithm redistributed the stresses by weighted spatial averaging. When damage accumulation was computed based on averaged stresses, the crack propagation rates predicted were independent of the level of mesh refinement. The critical distance, a parameter governing the effect of the averaging algorithm, was optimized such that the predicted crack propagation rates accurately corresponded to the experimental ones. These results are important for the validity and standardization of pre-clinical testing methods for orthopaedic implants.

Mechanical strength of the cement-bone interface is greater in shear than in tension.

The objective of this study was to determine the relative mechanical properties of the cement-bone interface due to tensile or shear loading. Mechanical tests were performed on cement-bone specimens in tensile (n = 51) or shear (n = 55) test jigs under the displacement control at 1 mm/min until complete failure. Before testing, the quantity of bone interdigitated with the cement was determined and served as a covariate in the study. The apparent strength of the cement-bone interface was significantly higher (p < 0.0001) for the interface when loaded in shear (2.25 MPa) when compared to tensile loading (1.35 MPa). Significantly higher energies to failure (p < 0.0001) and displacement before failure (p < 0.01) were also determined for the shear specimens. The post-yield softening response was not different for the two test directions. The data obtained herein suggests that cement-bone interfaces with equal amounts of tensile and shear stress would be more likely to fail under tensile loading.

Tensile strength of the cement-bone interface depends on the amount of bone interdigitated with PMMA cement.

An experimental investigation was performed to (1) determine the general mechanical behavior and in particular, the post-yield behavior of the cement-bone interface under tensile loading, (2) determine where interface failure occurs, and (3) determine if the mechanical properties of the interface could be related to the density of bone at the interface and/or the amount of cement-bone interdigitation. Seventy-one cement-bone test specimens were machined from human proximal femurs that had been broached and cemented using contemporary cementing techniques. The amount of cement-bone interdigitation was documented and the quantitative computed tomography equivalent mineral density (QCT density) of the bone with cement was measured. Specimens were loaded to failure in tension under displacement control and exhibited linear elastic behavior with some reduction in stiffness until the peak tensile stress was reached (1.28 +/- 0.79 MPa). A substantial amount of strain softening (negative tangent stiffness) with an exponential-type decay was found after the peak stress and continued until there was complete debonding of the specimens (at 0.93 +/- 0.44 mm displacement). Interfacial failure most often occurred at the extent of cement penetration into the bone (56% of specimens) or with small spicules of cement left in the bone (38% of specimens). The results showed that the post-yield tensile behavior contributes substantially to the energy required to cause failure of the cement-bone interface, but the post-yield behavior was not well correlated with the amount of interdigitation or density of bone. Linear regression analysis revealed a moderate (r2 = 0.499, p < 0.0001) positive relationship between the tensile strength of the cement-bone interface and the quantity of bone interdigitated with the cement.

Coulomb frictional interfaces in modeling cemented total hip replacements: a more realistic model.

Loosening of cemented femoral hip stems could be initiated by failure of the cement mantle due to high cement stresses. The goals of this study were to determine if realistic stem-cement interface characteristics could result in high cement stresses when compared to a bonded stem-cement interface and to determine if stem design parameters could be chosen to reduce peak cement stresses. Three-dimensional finite-element models of cemented femoral hip components were studied with bonded or realistic Coulomb friction stem-cement interfaces. The results showed that the use of a non-bonded, non-linear Coulomb friction interface resulted in substantially different stress fields in the cement when compared to a bonded stem-cement interface. Tensile stresses in the proximal cement mantel for the Coulomb friction interface case (10.8 MPa) were greater than the fatigue strength of the cement. In contrast, the tensile stresses in the cement mantle were not greater than the fatigue strength for the bonded case (7.5 MPa). Failure of the cement mantle in the proximal femur could therefore be initiated by a lack of a bond at the stem-cement interface. The effect of different cross-sectional stem geometries (medial radii of 3.0, 4.9 and 5.5 mm and antero-posterior widths of 9.8 and 13.7 mm) and different elastic moduli (cobalt chromium alloy and titanium alloy) for the stem material were also evaluated for models with a Coulomb friction interface. Changes in the stem cross-section and elastic modulus had only limited effects on the stress distributions in the cement. Of the parameters evaluated in this study, the characteristics of the stem-cement interface had the largest effect on cement mantle stresses.

Reduction of the intracanal fragment in experimental burst fractures.

An experimental investigation was carried out to create burst fractures and to evaluate the mechanisms and degree of reduction of the intracanal fragment with posterior instrumentation techniques in multisegmental human cadaver specimens. Reduction of the spinal fragment through kyphosis correction and distraction was evaluated using CT imaging. With kyphosis correction alone there was no decrease in canal compromise; in some cases there was a slight increase in canal compromise. Distraction, whether applied before or after kyphosis correction was the effective mechanism in reducing the fracture fragment. Kyphosis correction applied after distraction did not reduce the fragment further. Posterior devices that are used to treat burst fractures of the thoracolumbar spine with intracanal fragments should provide some form of distraction.

A biomechanical investigation of short segment spinal fixation for burst fractures with varying degrees of posterior disruption.

A biomechanical study was performed to evaluate the effectiveness of the Fixateur Interne pedicle screw system and the Syracuse I-Plate anterior fixation system. A total of 12 fresh frozen cadaver spines were tested intact, after burst fracture was created and application of a fixation device (six each), and after six serial transections of posterior ligaments and bony structures. Spines were loaded to a maximum of 10 N-m in flexion, extension, left and right lateral bending, and clockwise and counter-clockwise rotation. Results indicate that both systems reduce spinal flexibility in flexion, extension, and lateral bend loading when used to reduce and fix a classic burst fracture without posterior disruption. No decrease in flexibility was found in axial rotation for either device. After transection of all posterior elements, the I-Plate construct became much more flexible than the intact spine in flexion, extension, and axial rotation loading. The internal fixator construct retained more stability than the I-Plate construct after transection of posterior elements in flexion and extension loading, but was considerably more flexible than the intact spine in axial rotation loading. The results imply that the posterior internal fixator provides much better stabilization than the anterior I-Plate for those cases in which there is a large amount of posterior disruption in addition to an anterior burst injury. Neither device provides extensive support in axial rotation loading.

Early clinical experience with the Syracuse I-Plate: an anterior spinal fixation device.

Sixteen patients were treated with a new anterior internal fixation device after thoracolumbar or lumbar decompression, and fusion with bone grafting. Ten patients had acute burst fractures, four had metastatic tumors, and two had old, healed fractures with deformity. In the acute fracture group, eight patients had neurologic deficits and seven patients experienced improvement. Six patients had lesions of the conus medullaris, all of which improved. The four patients with metastatic tumors underwent surgery for back and leg pain and all gained significant relief. Two patients had correction of old fracture deformity with satisfactory outcome. Complications were minimal. The new anterior stabilization device provided early stability, allowed early patient mobilization, was easy to insert, and has a low profile. Late collapse, non-union, and kyphotic deformity have not been noted thusfar.

The influence of surface roughness on stem-cement gaps.

We have compared the interface morphology at the stem-cement interface of standard Charnley stems with a satin finish (Ra = 0.75 microm) with identical stems which had been grit-blasted over their proximal third (Ra = 5.3 microm) to promote a proximal bond. The stems were cemented into cadaver femora using conventional contemporary cementing techniques. After transverse sectioning, we determined the percentage of the perimeter of the stem which had a gap at the interface. There were substantial gaps (mean 31.4 +/- 17.1%) at the stem-cement interface in the grit-blasted region. This fraction was significantly (paired t-test, p = 0.0054) higher than that found around the contralateral satin-finished stems (mean 7.7 +/- 11.7%). Although studies of isolated metal-cement interfaces have shown that the bond strength can increase with surface roughness it cannot be assumed that this effect will be observed under clinical conditions.

Effects of sodium hyaluronate on tendon healing and adhesion formation in horses.

Sodium hyaluronate reduces adhesions after tendon repair in rodents and dogs, and has been used in limited clinical trials in people. To evaluate its effect on tendon healing and adhesion formation in horses and to compare these effects with those of a compound of similar visco-elastic properties, a study was performed in horses, using a model of collagenase injection in the flexor tendons within the digital sheath. Eight clinically normal horses were randomly allotted to 2 groups. Adhesion formation between the deep digital flexor tendon and the tendon sheath at the pastern region was induced in the forelimbs of all horses. Using tenoscopic control, a 20-gauge needle was inserted into the deep digital flexor tendon of horses under general anesthesia and 0.2 ml of collagenase (2.5 mg/ml) was injected. The procedure was repeated proximally at 2 other sites, spaced 1.5 cm apart. A biopsy forceps was introduced, and a 5-mm tendon defect was created at each injection site. Group-A horses had 120 mg of sodium hyaluronate (NaHA) gel injected into the tendon sheath of one limb. Group-B horses had methylcellulose gel injected at the same sites. The contralateral limbs of horses in both groups served as surgical, but noninjected, controls. Horses were euthanatized after 8 weeks of stall rest. Ultrasonographic evaluation revealed improved tendon healing after NaHa injection, but no difference in peritendinous adhesion formation. Tendon sheath fluid volume and hyaluronic acid (HA) content were greater in NaHA-treated limbs. Gross pathologic examination revealed considerably fewer and smaller adhesions when limbs were treated with NaHA. However, significant difference in pull-out strengths was not evident between NaHA-treated and control limbs. Histologically, the deep digital flexor tendon from the NaHA-treated limbs had reduced inflammatory cell infiltration, improved tendon structure, and less intratendinous hemorrhage. Treatment with methylcullulose had no significant effect on tendon healing, adhesion size, quantity, or strength or on the volume and composition of the tendon sheath fluid. Sodium hyaluronate, administered intrathecally, appears to have a pharmaceutically beneficial action in this collagenase-induced tendinitis and adhesion model in horses.