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Tendon overuse injuries are common athletic and occupational problems. When studying mechanisms that cause these injuries, inherent complexities associated with controlling in vivo loading necessitates alternative approaches such as in vitro organ culture. Current devices for loading explants in organ culture, whether custom-built or commercial, have various deficiencies in their loading capability, control mechanism and strain assessment. To overcome these shortcomings, an advanced tissue loading device with video strain analysis capabilities was developed for investigating overuse injuries and its performance/calibration were evaluated. Two tests were used to assess the ability of the system to create and monitor mechanical changes with overuse. Overuse loading significantly increased strains and decreased strength, showing the ability of this system to create and monitor tissue damage. Furthermore, the device design allows for its use in a standard incubator. Coupled with custom loading and data collection programs, this system is suitable for long-term overuse injury studies.

Background: Studies have suggested that some nonselective nonsteroidal anti-inflammatory drugs, including piroxicam, may improve ligament healing, whereas other nonsteroidal anti-inflammatory drugs, including ibuprofen and the cyclooxygenase-2 inhibitor celecoxib, may have no effect on the mechanical properties or may even deter the healing process. These results might reflect variations in cyclooxygenase enzyme selectivity by different drugs or, alternatively, may be related to their analgesic properties because it is generally accepted that early activity improves ligament healing., Hypothesis: Nonselective nonsteroidal anti-inflammatory drugs improve ligament healing, whereas other analgesics provide lesser degrees of improvement, and cyclooxygenase-2 inhibitors are detrimental., Study Design: Controlled laboratory study., Methods: One hundred fifty-five Sprague-Dawley rats were divided into 7 treatment groups (piroxicam, naproxen, rofecoxib, butorphanol, 2 doses of acetaminophen, and control). The right medial collateral ligament of each rat was transected, and the drugs were administered postoperatively on days 1 to 6. On day 14, the rats were sacrificed, and mechanical testing was performed on the medial collateral ligament., Results: The piroxicam group demonstrated significantly greater load to failure (27%) compared with the control. No significant differences were observed between other groups., Conclusions: Piroxicam improves ligament healing, but this effect cannot be attributed to all nonselective nonsteroidal anti-inflammatory drugs. Opiate analgesics, acetaminophen, and cyclooxygenase-2 inhibitors do not appear to categorically affect ligament healing., Clinical Relevance: In the treatment of ligament injury, piroxicam may be a drug of choice.

Background: Nonsteroidal anti-inflammatory drugs are frequently used to treat muscle injuries in athletes. It is not known whether the anti-inflammatory effects of these drugs are important or whether their effectiveness is a result of their central analgesic effect., Hypothesis: The effects of nonsteroidal anti-inflammatory drugs are no different than the effects of an analgesic (acetaminophen) without anti-inflammatory action in an experimental, acute muscle contusion model., Study Design: Controlled animal study., Methods: A standardized, unilateral, nonpenetrating injury was created to the tibialis anterior muscle of 96 adult male mice. Four treatment groups were used: group 1, placebo treatment; group 2, treatment with rofecoxib, a nonsteroidal anti-inflammatory drug with cyclooxygenase-2 selectivity, and treatment after the injury; group 3, rofecoxib treatment starting 24 hours before the injury; and group 4, acetaminophen treatment after the injury. The muscle and the contralateral normal muscle were evaluated at 2, 5, and 7 days after injury by grading of gait, wet weight as a measure of edema, and histologic evaluation., Results: Group 1 had significantly more gait disturbances at day 2 than all other groups (P < .05). No differences were found at days 5 and 7. Wet weights showed an increase at day 2 in group 1 (P < .01). Again, no differences were found at days 5 and 7. Histology revealed similar inflammatory changes at day 2 in all groups, with regeneration of muscle fibers at days 5 and 7., Conclusions: The results indicate that rofecoxib as a nonsteroidal anti-inflammatory drug and acetaminophen as a non-nonsteroidal anti-inflammatory drug analgesic have similar effects. The lack of differences in wet weights and histology suggests that the anti-inflammatory effects of rofecoxib are not an important feature of its action., Clinical Relevance: The routine use of nonsteroidal anti-inflammatory drugs in muscle injuries may need to be critically evaluated because low-cost and low-risk analgesics may be just as effective.

Objective: To determine the in vitro elastic limit of avian flexor tendons utilizing more current methodologies., Design: Assess the mechanical changes between subfailure and subsequent failure ramps at various loading levels., Background: Currently accepted values of elastic strain limits were determined utilizing older methodologies. Consequently, reported values are fairly small and imply matrix damage occurs with small strains., Methods: Flexor tendons were loaded in vitro, to various subfailure strain levels between 1% and 14%, allowed to rest for 5 min, then taken to failure. Suture markers, across the midsubstance, and cryo-grip displacement were monitored for strain using a video strain analysis system and a linear variable displacement transducer, respectively. The mechanical changes between the various subfailure and failure ramp loadings were assessed., Results: Varying strains of subfailure ramp loading did not influence (P>0.05) the ultimate tensile failure strength, elastic modulus, strain at failure, or strain energy density of tendons. In addition, residual strain after subfailure loading was not significant, nor was it influenced by the level of the subfailure loading., Conclusions: Tendon behaves elastically under ramp loading to significantly higher strains (nearly failure) than previously reported (4%)., Relevance: This study has found strain thresholds required to cause matrix damage to be significantly higher than previously thought, implying that matrix changes to acute loading events are more a result of the cellular response to the loading event. The clinical relevance is that the clinician may have a greater opportunity to prevent matrix changes than once thought by biochemically altering the cellular response.

Mechanical forces regulate the developmental path and phenotype of a variety of tissues and cultured cells. Vibratory loading as a mechanical stimulus occurs in connective tissues due to energy returned from ground reaction forces, as well as a mechanical input from use of motorized tools and vehicles. Structures in the spine may be particularly at risk when exposed to destructive vibratory stimuli. Cells from many tissues respond to mechanical stimuli, such as fluid flow, by increasing intracellular calcium concentration ([Ca(2+)](ic)) and releasing adenosine 5'-triphosphate (ATP), extracellularly, as a mediator to activate signaling pathways. Therefore, we examined whether ATP is released from rabbit (rAN) and human (hAN) intervertebral disc annulus cells in response to vibratory loading. ATP release from annulus cells by vibratory stimulation as well as in control cells was quantitated using a firefly luciferin-luciferase assay. Cultured hAN and rAN cells had a basal level of extracellular ATP ([ATP](ec)) in the range of 1-1.5 nM. Vibratory loading of hAN cells stimulated ATP release, reaching a net maximum [ATP] within 10 min of continuous vibration, and shortly thereafter, [ATP] declined and returned to below baseline level. [ATP] in the supernatant fluid of hAN cells was significantly reduced compared to the control level when the cells received vibration for longer than 15 min. In rAN cells, [ATP] was increased in response to vibratory loading, attaining a level significantly greater than that of the control after 30 min of continuous vibration. Results of the current study show that resting annulus cells secrete ATP and maintain a basal [ATP](ec). Annulus cells may use this nucleotide as a signaling messenger in an autocrine/paracrine fashion in response to vibratory loading. Rapid degradation of ATP to ADP may alternatively modulate cellular responses. It is hypothesized that exposure to repetitive, complex vibration regimens may activate signaling pathways that regulate matrix destruction in the disc. As in tendon cells, ATP may block subsequent responses to load and modulate the vibration response. Rabbit annulus cells were used as a readily obtainable source of cells in development of an animal model for testing effects of vibration on the disc. Human cells obtained from discarded surgical specimens were used to correlate responses of animal to human cells., (Copyright 2003 Wiley-Liss, Inc.)

Recent studies have emphasized that the etiology of tendinopathy is not as simple as was once thought. The etiology is likely to be multifactorial. Etiologic factors may include some of the traditional factors such as overuse, inflexibility, and equipment problems; however, other factors need to be considered as well, such as age-related tendon degeneration and biomechanical considerations as outlined in this article. More research is needed to determine the significance of stress-shielding and compression in tendinopathy. If they are confirmed to play a role, this finding may significantly alter our approach in both prevention and in treatment through exercise therapy. The current biomechanical studies indicate that certain joint positions are more likely to place tensile stress on the area of the tendon commonly affected by tendinopathy. These joint positions seem to be different than the traditional positions for stretching exercises used for prevention and rehabilitation of tendinopathic conditions. Incorporation of different joint positions during stretching exercises may exert more uniform, controlled tensile stress on these affected areas of the tendon and avoid stresshielding. These exercises may be able to better maintain the mechanical strength of that region of the tendon and thereby avoid injury. Alternatively, they could more uniformly stress a healing area of the tendon in a controlled manner, and thereby stimulate healing once an injury has occurred. Additional work will have to prove if a change in rehabilitation exercises is more efficacious that current techniques.

Objectives: This study determined the tensile properties of 18-gauge stainless steel wire, 5-mm woven polyester (Mersilene) tape, and multiple loop configurations of No. 5 braided polyester suture (Ethibond)., Design: Mechanical property testing., Intervention: Single loops of stainless steel wire, Mersilene, and Ethibond were tested to determine their mechanical properties. Ethibond was tested with different numbers of loops and different knot configurations., Main Outcome Measures: Stiffness, load at failure, and elongation at failure., Results: One loop of Mersilene and two loops of Ethibond had similar loads at failure, but the load at failure was significantly higher for stainless steel wire. Four loops of Ethibond withstood a similar failure load to stainless steel wire, but the failure load of the Ethibond suture was greater than the yield load of stainless steel wire. Stainless steel wire had a higher stiffness than both Ethibond and Mersilene. No difference was found in the failure load between different Ethibond knot configurations. The individually tied suture configuration resulted in a higher stiffness than the single-knot configuration. The elongation at failure was not statistically different among the different knot configurations and materials, with the exception of Mersilene tape. Mersilene tape demonstrated a significant increase in elongation at failure as compared to the other materials and knot configurations., Conclusion: It appears that multiple loops of Ethibond can substitute for stainless steel wire in situations where a compliant repair is suitable (support of a patellar tendon repair), but may not be satisfactory for rigid fixation (tension band fixation of a fracture). There appears to be no significant difference in strength but a small decrease in stiffness between tying multiple suture loops in one knot as opposed to individual knots.

Background Context: Whole body vibration is an important factor contributing to low back and radicular pain. Vibratory loading as a mechanical stimulus is transferred to connective tissues as energy from ground reaction forces, as well as a direct input from the use of motorized tools and vehicles. Extracellular matrix degradation parallels increased age and mechanical stimuli resulting in disc degeneration and eventual spinal deformity., Purpose: The objective of this study was to investigate the relationship between vibratory loading and extracellular matrix expression in cultured rabbit annulus cells., Study Design/setting: An in vitro rabbit model using cultured annulus fibrosis cells isolated from normal intervertebral disc was used to study matrix and metalloproteinase expression in response to vibration., Methods: Annulus fibrosis cells were isolated by collagenase digestion from New Zealand White rabbits. Vibratory stimulation was applied to annulus cells in vitro, using an oscillating platform to deliver 0.1 x gravity load at 6 Hz for 2, 4, 6 or 8 hours. Gene expression was assessed by reverse transcriptase polymerase chain reaction., Results: Aggrecan, collagen Type III and matrix metalloproteinase-3 gene expression was suppressed by vibratory loading in rabbit annulus cells. Suppression of the aggrecan gene might lead to a decrease in proteoglycan synthesis., Conclusions: These data suggest that vibratory load may play an important role in extracellular matrix metabolism of intervertebral disc cells, especially in the gene expression pathway of proteoglycans. It has been proposed that vibratory loading increases production of matrix-degrading, proteolytic enzymes. We have demonstrated that gene expression for key matrix messages and matrix metalloproteinase is decreased by vibration. In conclusion, we believe that study of the roles between extracellular matrix gene suppression and mechanical stress may clarify the pathomechanism of disc degeneration, such as disc herniation or degeneration.

This study investigated the strain pattern in human patellar tendon in an area of the tendon where changes commonly associated with patellar tendinitis are found. Eight fresh frozen human knees were instrumented with strain gauges on both the anterior and posterior side of the proximal patellar tendon. Both static and dynamic measurements were carried out in a range from 0 degrees to 60 degrees of flexion. We found uniform tensile strain in the tendon with the knee in full extension. However, as the knee was brought into flexion, the tensile strain increased on the anterior side but decreased on the posterior side in the central, proximal location of the tendon. The posterior side of the proximal patellar tendon is most commonly affected in patellar tendinopathy. This study indicates that this area of the tendon may not subjected to the highest tensile loads in the functional flexion range. It is possible that stress shielding is more important etiological factor in insertional tendinopathy as opposed to repetitive tensile loads.

Celecoxib was the first of a new class of nonsteroidal antiinflammatory drugs, the cyclooxygenase-2 (COX-2) specific inhibitors, marketed as having the same antiinflammatory efficacy as other nonsteroidal antiinflammatory drugs without their increased risk of gastrointestinal ulceration. Among the widest uses of nonsteroidal antiinflammatory drugs is in the treatment of acute soft tissue injuries. Although the benefits of celecoxib have been shown when used for rheumatoid arthritis and osteoarthritis, we are unaware of any studies concerning its effect on soft tissues. We used the surgically incised medial collateral ligament of male Sprague-Dawley rats as an experimental model for acute ligament injuries to investigate the effects of celecoxib on ligament healing. Fifty rats underwent surgical transection of the right medial collateral ligament. Postoperatively, half were given celecoxib for the first 6 days of recovery, the other half were not. The animals were sacrificed 14 days after the operation, and both the injured and uninjured medial collateral ligaments were mechanically tested to failure in tension. Celecoxib-treated/injured ligaments were found to have a 32% lower load to failure than untreated/injured ligaments. The results of this study do not support use of cyclooxygenase-2 specific inhibitors in the treatment of ligament injuries.

A simplified three-dimensional simulation of trabecular bone remodeling has been developed. The model utilizes 441 planar structural units to represent approximately 50 mm3 of initial bone volume with 199 basic multicellular units (BMUs). The simulation takes into account trabecular perforation in the structural model. The cases of male bone remodeling with no menopause and female bone remodeling with menopause are examined from the period of simulated age 25-80 years. Menopause is arbitrarily started at age 45 and extends for 7.5 years. Zero-, first-, and second-order BMU activation responses are employed to examine how the bone would be affected by the method of increase of BMU activation during menopause. At age 80, the female bone remodeling simulation produced a bone volume loss of approximately 49% for all three activation responses. This compared to a 38% bone volume loss for the case of no menopause. For the menopause simulations, an average of about 40% of the total bone loss was due to perforation.

The ovariectomized ewe is being used as an animal model for postmenopausal osteoporosis. Data on the mechanical properties of ewe vertebral cancellous bone is needed to assess its effectiveness as a model for vertebral osteoporosis. This study utilized traditional compression testing and a novel nondestructive vibrational testing method to assess the directional mechanical properties of ewe vertebral cancellous bone. Composition and density properties were also assessed. It was hypothesized that vibrational testing would have utility in that it would allow for the anisotropic stiffness of cancellous bone to be assessed nondestructively. The present study has found that ewe vertebral cancellous bone has similar physical and mechanical properties to humans. The vibrational testing method described was able to nondestructively provide a valid measure of stiffness that was correlated with stiffness estimates from traditional compression testing. Furthermore, the stiffness measure from the vibration test was found to be sensitive to the architecture of cancellous bone. These results suggest the promise of this testing method for the nondestructive mechanical assessment of skeletal tissue.

Objective: To assess the viability of using a modified flexible suture implant instead of a tricortical screw for fixation of ankle syndesmosis failures., Design: Randomized biomechanical study., Setting: Orthopaedic Research Laboratories at the University of North Carolina at Chapel Hill., Intervention: Formalin-preserved cadaveric legs were used in pairs. Two holes, 2.5 millimeters in diameter and 7.0 to 10.0 millimeters apart horizontally, were drilled through the fibula and tibia 2.0 centimeters above the tibial plafond. Two strands of Number 5 suture were passed through the holes and tied. Similarly, a 3.5-millimeter tricortical screw was placed on the opposite leg of each pair at 2.0 centimeters. The ankles were tested to failure. This process was repeated at 5.0 centimeters above the tibial plafond., Main Outcome Measurements: Maximum load and displacement at failure of the suture construct at 2.0 centimeters and at 5.0 centimeters were compared with a tricortical screw at 2.0 centimeters and at 5.0 centimeters., Results: There was no significant difference in strength or displacement between the flexible suture implant and the tricortical screw at either 2.0 centimeters or 5.0 centimeters. The fixations at 5.0 centimeters had significantly increased holding strength over fixations at 2.0 centimeters, and the fixations had significantly greater displacement at 2.0 centimeters than at 5.0 centimeters., Conclusion: This study confirms that flexible syndesmosis repair is a viable option for internal fixation of ankle mortise instability due to syndesmosis rupture.

After menopause, bone turnover is increased due to an increase in the activation of bone remodeling basic multicellular units (BMUs). The importance of changes in BMU activation to bone histomorphometry data and bone volume has not received adequate attention by many skeletal researchers. Therefore, the influence of BMU activation on the above parameters was modeled by way of computer simulation, and the results were compared to data from published post-menopausal bone loss studies. Using control theory concepts, the increase in BMU activation after menopause was modeled as a zero-, first-, or underdamped (oscillatory) second-order transient BMU activation response to the step input: the decline in estrogen. A computer simulation was developed to model the influence of these three transient BMU activation responses on quantitative histological surface parameters and bone volume. The transient BMU activation responses doubled the number of active BMUs. All three types of transient BMU activation responses produced a rapid 5% decline in bone volume due to increased remodeling space. Oscillations in bone volume and histologic surface parameters over time, similar in nature to those seen in studies of ovariectomized animals, were predicted by the simulation for the oscillatory activation response examined, underdamped second order. An oscillatory BMU activation response may explain some of the transient events during menopause. The increased coherence of BMUs created by such a response may increase the likelihood of trabecular perforations. the inherent nature of an oscillatory activation response may cause its detection to be overlooked and bone remodeling data to be misinterpreted.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells in the body are constantly subjected to cyclic mechanical deformation involving tension, compression, or shear strain or all three. A mechanical loading system which deforms cultured cells in vitro was analyzed in order to quantify the deformation or strain to which the cells are subjected. The dynamic system utilizes vacuum pressure to deform a circular silicone rubber substrate on which cells are cultured. These thick circular growth surfaces or plates are formed in the bottoms of the wells of 6-well culture plates. An axisymmetric model was formulated and analyzed using rectangular hyperelastic elements in a finite element analysis (FEA) software package. The thick circular plate has some disadvantages such as difficulty in observing cells and a nonhomogeneous strain profile which is maximum at the periphery and minimal at the center. A thinner circular surface (a thin plate) was also investigated in order to provide a more homogeneous strain profile. The radial strain on the thick circular plate, as determined by FEA, was nonlinear with a peak strain value of 0.30 (vacuum pressure of 22 kPa) about three-quarters of the distance from the center to the edge. In contrast, the radial strain of the thin circular plate was moderately constant across the surface. The circumferential strain for both of these models was less than the radial strain except for the center where they are equal. Avian tendon cells were cultured on the surface of a thick plate and exposed to cyclic strains for 24 h at a rate of 0.17 Hz and observed for cellular alignment.(ABSTRACT TRUNCATED AT 250 WORDS)