Modulation of fixation stiffness from flexible to stiff in a rat model of bone healing.

Background and purpose - Constant fixator stiffness for the duration of healing may not provide suitable mechanical conditions for all stages of bone repair. We therefore investigated the influence of stiffening fixation on callus stiffness and morphology in a rat diaphyseal osteotomy model to determine whether healing time was shortened and callus stiffness increased through modulation of fixation from flexible to stiff. Material and methods - An external unilateral fixator was applied to the osteotomized femur and stiffened by decreasing the offset of the inner fixator bar at 3, 7, 14, and 21 days after operation. After 5 weeks, the rats were killed and healing was evaluated with mechanical, histological, and microcomputed tomography methods. Constant fixation stiffness control groups with either stiff or flexible fixation were included for comparison. Results - The callus stiffness of the stiff group and all 4 experimental groups was greater than in the flexible group. The callus of the flexible group was larger but contained a higher proportion of unmineralized tissue and cartilage. The stiff and modulated groups (3, 7, 14, and 21 days) all showed bony bridging at 5 weeks, as well as signs of callus remodeling. Stiffening fixation at 7 and 14 days after osteotomy produced the highest degree of callus bridging. Bone mineral density in the fracture gap was highest in animals in which the fixation was stiffened after 14 days. Interpretation - The predicted benefit of a large robust callus formed through early flexible fixation could not be shown, but the benefits of stabilizing a flexible construct to achieve timely healing were demonstrated at all time points.

Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue.

The free radical theory of aging postulates that the production of mitochondrial reactive oxygen species is the major determinant of aging and lifespan. Its role in aging of the connective tissue has not yet been established, even though the incidence of aging-related disorders in connective tissue-rich organs is high, causing major disability in the elderly. We have now addressed this question experimentally by creating mice with conditional deficiency of the mitochondrial manganese superoxide dismutase in fibroblasts and other mesenchyme-derived cells of connective tissues in all organs. Here, we have shown for the first time that the connective tissue-specific lack of superoxide anion detoxification in the mitochondria results in reduced lifespan and premature onset of aging-related phenotypes such as weight loss, skin atrophy, kyphosis (curvature of the spine), osteoporosis and muscle degeneration in mutant mice. Increase in p16(INK4a) , a robust in vivo marker for fibroblast aging, may contribute to the observed phenotype. This novel model is particularly suited to decipher the underlying mechanisms and to develop hopefully novel connective tissue-specific anti-aging strategies.

Meniscal screw fixation provides sufficient stability to prevent tears from gapping.

BACKGROUND: Many meniscal fixation implants have low pull-out forces. It is still unknown if these forces are higher than the forces the implants must resist in vivo. It was hypothesized that meniscal repair with the meniscal screw as an example for a device of low pull-out force significantly reduces tear gapping. METHODS: Longitudinal tears were set in the posterior horn of the medial menisci of porcine knee joints. To observe the tears a translucent placeholder copying the original articular surface replaced the medial tibial plateau. The knees were moved in a loading and motion simulator under various external moments and axial loads and gapping of the tear was registered. The measurements were repeated after fixation of the tears with three ClearFix Screws, which show a low pull-out force of 20N only. FINDINGS: Maximum gapping (median 1.6mm, min/max 1.1/1.8mm) occurred at 200N axial joint load under the combination of a valgus and external rotation moment. Fixation with the ClearFix Screw significantly reduced tear gapping in all load cases. INTERPRETATION: Moderate joint loads only lead to small gaps of meniscal tears. Meniscal fixation with the ClearFix Screw prevents longitudinal meniscal tears from gapping. This could indicate from a biomechanical point of view that fixation implants of low pull-out strength are not in danger of failure in a normal rehabilitation regimen.

Biomechanical evaluation of vertebroplasty and kyphoplasty with polymethyl methacrylate or calcium phosphate cement under cyclic loading.

STUDY DESIGN: We developed a new method to simulating in vivo dynamic loading as closely as possible, which allows comparison of kyphoplasty and vertebroplasty, as well as augmentation materials. OBJECTIVE: Special interest was given to calcium phosphate cement, which might fail due to its brittleness. SUMMARY OF BACKGROUND DATA: Vertebroplasty and kyphoplasty are, with limitations, 2 promising alternative techniques to augment osteoporotic vertebrae with polymethyl methacrylate or calcium phosphate cements. However, little is known about the fatigue characteristics of the treated vertebrae under cyclic loading. METHODS: Twenty-four intact, osteoporotic bi-segmental human specimens were divided into 4 groups: (1) vertebroplasty with polymethyl methacrylate, (2) kyphoplasty with polymethyl methacrylate, (3) kyphoplasty with calcium phosphate cement, and (4) untreated control group. After augmentation of the middle vertebrae, all specimens underwent 100,000 cycles of eccentric loading during which the specimen revolved around its longitudinal axis. Pre-loading and post-loading radiographs, and subsidence measurements at different sites of the vertebrae were taken. The overall height was additionally determined every 20,000 cycles in the material testing machine. Finally, the specimens were cryosectioned to examine the cements. RESULTS: Loss of height progressed with strong individual differences in all groups, with an increasing number of load cycles up to median values of 2.8 mm for both augmented groups and 4.2 mm for the nonaugmented group. At the center of the upper endplate, subsidence in kyphoplasty was greater than in vertebroplasty, with little differences with respect to the kind of cement. The cryosections did not show any signs of fatigue in the polymethyl methacrylate, but small cracks were in the calcium phosphate. CONCLUSIONS: Vertebroplasty and kyphoplasty seem to be equivalent methods in strengthening osteoporotic vertebrae. However, these results cannot be transferred to the treatment of fractures with these methods. A "physiologic" loading situation was achieved by complex motion, including all combinations of flexion/extension with lateral bending during eccentric cyclic loading.

Regulation of gene expression in intervertebral disc cells by low and high hydrostatic pressure.

Intervertebral disc structures are exposed to wide ranges of intradiscal hydrostatic pressure during different loading exercises and are at their minimum during lying or relaxed sitting and at maximum during lifting weights with a round back. We hypothesize that these different loading magnitudes influence the intervertebral disc (IVD) by alteration of disc matrix turnover depending on their magnitudes. Therefore the aim of this study was to assess changes in gene expression of human nucleus cells after the application of low hydrostatic pressure (0.25 MPa) and high hydrostatic pressure (2.5 MPa). IVD cells isolated from the nucleus of human (n = 18) and bovine (n = 24 from four animals) disc biopsies were seeded into three-dimensional collagen type-I matrices and exposed to the different loading magnitudes by specially developed pressure chambers. The lower pressure range (0.25 MPa, 30 min, 0.1 Hz) was applied with a recently published device by using an external compression cylinder. For the application of higher loads (2.5 MPa, 30 min, 0.1 Hz) the cell-loaded collagen gels were sealed into sterile bags with culture medium and stimulated in a newly developed water-filled compression cylinder by using a loading frame. These methods allowed the comparison of loading regimes in a wide physiological range under an equal three-dimensional culture conditions. Cells were harvested 24 h after the end of stimulation and changes in the expression of genes known to influence IVD matrix turnover (collagen-I, collagen-II, aggrecan, MMP1, MMP2, MMP3, MMP13) were analyzed by real-time RT-PCR. A Wilcoxon signed-rank test(1) and a Wilcoxon 2-sample test(2) were performed to detect differences between the stimulated and control samples(1) and differences between low and high hydrostatic pressure(2). Multiple testing was considered by adjusting the p value appropriately. Both regimes of hydrostatic pressure influenced gene expression in nucleus cells with opposite tendencies for the matrix forming proteins aggrecan and collagen type-I in response to the two different pressure magnitudes: Low hydrostatic-pressure (0.25 MPa) tended to increase collagen-I and aggrecan expression of human nucleus cells (P < 0.05) but only to a small degree. High hydrostatic pressure (2.5 MPa) tended to decrease gene expression of all anabolic proteins with significant effects on aggrecan expression of nucleus cells (P = 0.004). Low hydrostatic pressure had no influence on the expression of matrix metalloproteinases (MMP1, MMP2, MMP3 and MMP13). In contrast, high hydrostatic pressure tended to increase the expression of MMP1, MMP3 and MMP13 of human nucleus cells with high individual-individual variations. The decreased expression of aggrecan (P = 0.008) and collagen type II (P = 0.023) and the increased MMP3 expression (P = 0.008) in response to high hydrostatic pressure could be confirmed in additional experiments with bovine nucleus cells. These results suggest that hydrostatic pressure as one of the physiological stimuli of the IVD may influence matrix turnover in a magnitude dependent way. Low hydrostatic pressure (0.25 MPa) has quite small influences with a tendency to anabolic effects, whereas high hydrostatic pressure (2.5 MPa) tends to decrease the matrix protein expression with a tendency to increase some matrix-turnover enzymes. Therefore, hydrostatic pressure may regulate disc matrix turnover in a dose-dependent way.

Changes in strain distribution of loaded proximal femora caused by different types of cementless femoral stems.

BACKGROUND: A number of clinically used total hip femoral implants are claiming a more or less physiologic load transfer, mostly without providing experimental data. To compare three clinically cementless total hip stems of fundamentally different design, the strain distribution before and after insertion in human cadaver femora was measured in vitro. METHODS: A conventional straight stem based on a distal anchorage concept, a so-called "anatomic" stem designed to have a proximal force transmission and a "stemless" femoral neck prosthesis were evaluated under similar loading conditions. Strain distribution was measured with tri-axial strain-gauge rosettes before and after implantation of the stems. The same bending moment was used in all femora tested to compare magnitude and direction of the resulting strains. FINDINGS: The straight and the "anatomic" stem both led to a decrease of the longitudinal strains in the proximal femur, while the femoral neck implant mainly led to an increase of measured strains on the lateral side of the greater trochanter. The observed medial strains were closer to physiological values in the "stemless" prosthesis than those of the two full-stem prosthesis. INTERPRETATION: The decrease in strains seen in the proximal region of the femora with implanted conventional hip prosthesis corresponds well to the decrease of bone density in this region noted in clinical follow-up studies. The more physiological strain at the inferior base of the neck seen in "stemless implant" may induce a remodelling process that better retains bone stock in that area. However, the increase of strains noted after implantation of this prosthesis require further investigation to assess the risk they may pose to bone failure.

Control of material stiffness during degradation for constructs made of absorbable polymer fibers.

Augmentation devices for cruciate ligament surgery should provide gradually decreasing mechanical properties with a half-time strength of at least 6 months to temporarily protect healing tendon grafts or sutured ligaments against high tensile loads during the postoperative healing period. The absorbable material of choice that shows such slow degradation kinetics is poly(L-lactide). However, previous studies have shown that poly(L-lactide) fulfills the requirement of a long half-time strength, while the corresponding stiffness decreases at a much slower rate. An augmentation stiffness that does not change much versus time cannot provide a gradual increase in graft load, which is important to stimulate the orientation of the collagenous tissue. Therefore a new augmentation device was designed, which should decrease both in strength and stiffness during degradation. The cord was braided out of two fibers made of poly(L-lactide) and poly(L-lactide-co-glycolide), which degrade at different rates. The cord prototype was degraded in vitro and the rupture force and stiffness was tested at eight different time points up to 60 weeks. The initial rupture force and stiffness was 522.7 +/- 2.8 N and 104.1 +/- 3.8 N/%, respectively. Both strength and stiffness decreased continuously with a half-time strength of 18 weeks and a half-time stiffness of 39 weeks. The gradually decreasing stiffness was achieved by the breakdown of the faster-degrading fiber component made of poly(L-lactide-co-glycolide). Thus the new augmentation device can provide a continuous increase of forces in a tendon graft or in a healing ligament.

Influence of preoperative mechanical bone quality and bone mineral density on aseptic loosening of total hip arthroplasty after seven years.

OBJECTIVE: To test mechanical bone quality and bone mineral density of the femoral head at the day of implantation as indicators for femoral prosthesis loosening. METHODS: Mechanical bone quality of a femoral head slice was assessed by destructive compression testing combined with bone mineral density measurements using peripheral quantitative computed tomography. Fourteen patients with walking pains were attainable for a radiographical follow-up mean 7.1 years after implantation. RESULTS: Radiolucent lines along the stem were evident in 11 of 14 femurs, most of them seen in Gruen zones 7, 6, 1, 3, 14, and showed strong correlations to preoperative bone strength (r=-0.80; P<0.001) and axial stiffness (r=-0.75; P=0.002), yet not to bone mineral density (r=-0.67; P=0.009). Slight varus deviations <3 degrees were noted in six femurs. Preoperative strength was reduced in this femurs to 54% (P=0.006), and stiffness to 61% (P=0.038), while bone mineral density did not differ significantly. CONCLUSIONS: Femoral prosthesis loosening after seven years can be predicted by mechanical bone quality of the femoral head at the time of implantation. Bone mineral density measurements may also indicate future stem loosening but have to interpreted carefully, keeping in mind a poorer predictive value. RELEVANCE: Indications and choice of type of hip arthroplasty should be balanced in osteoporotic bones in particular. While preoperative bone mineral density measurement allows the prediction of mechanical bone quality, its relevance in predicting failure in arthroplasty treatment remains unclear.

Gapping phenomenon of longitudinal meniscal tears.

OBJECTIVE: To investigate the gapping behaviour of longitudinal meniscal tears. DESIGN: The gap size of longitudinal meniscal tears was measured in porcine knee joints under various joint loading conditions. BACKGROUND: Many meniscal fixation implants have low pull out forces. However, it is unknown if these forces are less than the forces the implants must resist in vivo. It is also unknown if gapping occurs in longitudinally torn menisci and what joint loads induce gapping. METHODS: Longitudinal tears were set in the medial menisci of eight porcine knee joints. To observe the tears an opaque placeholder of the same shape as the original articular surface replaced the medial tibial plateau. The knees were exposed to flexion-extension cycles in a loading and motion simulator under 30 and 200 N axial joint load without external moments, under tibial rotation moments, varus or valgus moments, and combined moments. For each load condition the maximum gap of the tear was registered. RESULTS: Maximum gapping (1.59 mm, SD 0.47) occurred in the 3 cm tear at 200 N axial joint load under the combination of a valgus and external rotation moment. An internal tibial rotation moment produced the smallest gaps in tears of any length and at any axial joint load. CONCLUSIONS: The maximum gap size found in this study and the previously published pull out stiffnesses of meniscal fixation implants reveal maximum forces on the implant in vivo of only 8.4 N. This explains why meniscal tears fixed with implants of low pull out strength can heal. RELEVANCE: The current study shows that moderate joint loads only lead to small gaps of meniscal tears. Clinically, this means that fixation implants of low pull out strength are not in danger of failure in a normal rehabilitation regimen.

Cyclic joint loading can affect the initial stability of meniscal fixation implants.

OBJECTIVE: To identify the effect of cyclic joint loads on the initial fixation strength of different meniscal repair techniques. DESIGN: Three different meniscal refixation implants and one suturing technique were tested for initial stability in porcine knee joints after cyclic joint loading. BACKGROUND: Existing studies tested the initial pull out strength of meniscal fixation implants. It remains unknown how such implants perform under cyclic joint loading. METHODS: The Meniscal Fastener, the Meniscal Arrow, the ClearFix Screw, and a horizontal suture (PDS 1) were implanted in 64 porcine knee joints after setting a tear in the posterior horn of the medial meniscus. In one group of each device the menisci were excised directly after implantation and subsequently subjected to a pull out test. The knee joints of the other groups were exposed to 5000 axial load cycles between 10 and 200 N prior to the pull out test. RESULTS: The horizontal suture showed the highest pull out force (103 N, SD 19 N). Arrow (52 N, SD 18 N), Meniscal Fastener (29 N, SD 3 N), and Meniscal Screw (22 N, SD 8 N) failed at significantly lower loads. Cyclic loading led to a decreased initial pull out force only for the horizontal suture (82 N, SD 26 N) and the Meniscal Fastener (23 N, SD 5N). CONCLUSIONS: Cyclic joint loading can lead to reduced fixation strength especially of meniscal refixation implants and sutures with relatively low stiffness. However, it remains unclear which fixation strength is necessary to provide conditions for meniscal healing. RELEVANCE: The current study adds information to the understanding of how meniscal fixation systems perform mechanically especially after cyclic joint loads.

Effects of one-plane and two-plane external fixation on sheep osteotomy healing and complications.

OBJECTIVES: Comparison of one-plane and two-plane external fixation in terms of successful healing, incidence of complications, and biomechanical stability in a sheep model. BACKGROUND: Rigid fixation is preferred in open and comminuted fractures with a reduced blood supply, preventing infection and healing delay, but more often a flexible device is recommended even in unfavourable healing conditions. METHODS: The left tibiae of fifteen sheep were osteotomized and laterally fixed with a four-screw unilateral fixator frame (axial stiffness 183 N/mm) to a 3 mm gap size. In 9 of 15 sheep, an additional four-screw unilateral external fixator was anterolaterally attached (total axial stiffness of both frames 388 N/mm). After sacrificing, quality of osteotomy healing was assessed by mechanical and radiological evaluations. Osteogenesis was measured using fluorescence microscopy. RESULTS: Two distal fractures through the pin-tracks, three non-unions and four deep infections occurred after two-plane fixation. These failures excluded, osteotomy healing showed inferior results after two-plane fixation with reduced callus formation, bone mineral content, and bending stiffness amounts, respectively. Osteogenesis was halved following two-plane fixation in the remaining sheep. CONCLUSIONS: Two-plane fixation was not sufficient to reach successful osteotomy healing in our study. While higher rigidity was expected to prevent complications, healing in this group might have been disturbed by a reduced blood supply. The optimal stabilisation for a given fracture depends on many factors, including the biomechanical and biological environment. RELEVANCE: Considering our results and the literature discussed in this manuscript, good bone healing with minor risks of infections can be achieved using an unilateral one-plane fixator with only four screws, and its application on a muscle free position like the medial and anterior site of the sheep tibia.

A scanning electron microscopy study of human osteoblast morphology on five orthopedic metals.

Despite the long-standing use of metals as orthopedic implants there still are unsolved problems with these materials and open questions about their behavior in a biological environment. Cell-culture studies provide a useful tool for investigations. In addition to the determination of biochemical or molecular biological parameters, the morphology of adhering cells reflects their interaction with the substrata. This article describes an investigation of the morphology of human osteoblasts on stainless steel, cobalt chromium alloy, commercially pure titanium, Ti-6Al-4V, and Ti-6Al-7Nb with surface designs similar to those used as clinical implants. A cell culture plastic surface was used as a control material. The materials were examined by scanning electron microscopy at different points of time. The cells spread, proliferated, and formed nodules on all test substrates in a time-dependent manner, without signs of a disturbing influence from any of the materials. On the smooth surfaces the cells showed a flattened fibroblast-like morphology and only slight differences could be detected. Therefore, the cellular morphology seems not to be markedly affected by the different chemical material compositions. In contrast, the titanium alloy with a rough, sandblasted surface induced a three-dimensional growth. This three-dimensional cellular network could be the basis for the known earlier differentiation of osteoblasts on rough surfaces in vitro and a better osseointegration in vivo.