bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal patterns of stromelysin‐1, tissue inhibitor, and proteoglycan fragments in human knee joint fluid after injury to the cruciate ligament or meniscus
Authors: Stefan Lohmander L. , Roos Harald , Dahlberg Leif , Hoerrner Lori A. , Lark Michael W.
Published: February 2005

Stromelysin‐1, tissue inhibitor of metalloproteinases‐1 (TIMP‐1), and proteoglycan fragments were quantified in knee synovial fluid samples in a cross‐sectional study of patients who had injury to the anterior cruciate ligament or the meniscus. The average concentrations of stromelysin‐1 and TIMP‐1 increased 25‐fold and 10‐fold within the first day after the trauma, respectively, and the concentration of proteoglycan fragments increased 4‐fold. From approximately 1‐6 months after injury, the levels of these markers were higher after injury to the cruciate ligament than after injury to the meniscus. From 6 months to 18 years after trauma, however, the levels of stromelysin‐1 and TIMP‐1 in patients who had an injury to the ligament were the same as the levels in patients who had a meniscal lesion. but the levels were increased compared with those for a reference group of healthy volunteers. The molar balance of stromelysin‐1 to TIMP‐1 in synovial fluid in both groups of injured joints changed from a balance representing an excess of free inhibitor in the normal joint to one representing an excess of free enzyme in the injured joint. The increased release of these markers to joint fluid both early and late after trauma may be caused by a change in the loading patterns in the knee with an injured ligament or meniscus or by synovitis induced by bleeding. The increased release may be associated with the frequent development of posttraumatic osteoarthritis in patients with these injuries.
In vivo inflammatory response to polymethylmethacrylate particulate debris: Effect of size, morphology, and surface area
Authors: Gelb Howard , Ralph Schumacher H. , Cuckler John , Baker Daniel G.
Published: February 2005

Particulate debris, including that from polymethylmethacrylate (PMMA) cement, is observed commonly in the membrane surrounding loose joint prostheses. Such debris is assumed to cause an inflammatory response and contributes to osteolysis and failure of the implant. A subcutaneous rat air‐pouch model was used to assess quantitatively the in vivo effects of the size, morphology, and surface area of PMMA particles on the acute inflammatory response. PMMA particles were divided into three groups. In Group A, mechanical grinding of cured bone cement produced irregularly shaped particles; Group B included spherical particles of PMMA powder (Simplex P); and Group C consisted of commercially prepared spherical latex particles. All three groups had two size distributions: < 20 μm and 50–350 μm. For a given mass or dose, the small, irregularly shaped mechanically produced particles in Group A elicited a significantly greater inflammatory reaction than the large particles in Group A, as expressed by the release of tumor necrosis factor (TNF), neutral metalloprotease (NMP), and prostaglandin E2 (PGE2) and the white blood cell (WBC) count within a 24‐hour period. Similar findings were seen in Group B. Particles in Group C were used to compare the effect of absolute numbers of large and small particles and surface area. Large (10–126 μm) spherical PMMA particles at a dose of 1.7 × 106 particles/ml caused a significantly higher inflammatory response, as measured by WBC count and production of NMP and PGE2, than small (1–10 μm) spheres at a dose of 4 × 106 particles/ml. However, the production of TNF in the rats was significantly increased with small particles (p < 0.05) at a concentration 4‐fold less than that with the large particles (4 × 105 compared with 1.7 × 106 particles/ml). This finding may reflect a different cellular mechanism for the TNF component of the inflammatory response than is measured by WBC counts or by levels of PGE2 and NMP. As the calculated surface area of the PMMA particles increased, a threshold level was reached, at which point the inflammatory response increased dramatically. The size of particles has a role in the prolongation and intensity of the release of specific cytokines. The total surface area of the particles appeared to be an important factor in determining the inflammatory response, as measured by WBC count, PGE2, TNF, and NMP.
Sagittal configuration of the spine and growth of the posterior elements in early scoliosis
Authors: Xiong Bo , Sevastik John , Hedlund Rune , Sevastik Bo
Published: February 2005

The early changes of the sagittal alignment of the spine and the asymmetry between the posterior and anterior elements were determined on the basis of 134 lateral and 167 anteroposterior radiographs obtained from a control group and from patients with early scoliosis. The radiographs were allocated into four groups according to the degree of the Cobb angle. In thoracic curves with a Cobb angle of more than 8°, the kyphosis and the vertebral sagittal wedge angle decreased in comparison with the control group. The sagittal‐wedge angle of the disc did not change significantly with increasing Cobb angle. The pedicle height in relation to the vertebral height, considered to represent the growth of the posterior element in relation to the growth of the anterior element, was not significantly different in the scoliotic groups as compared with the control group. The results indicate that changes of the sagittal configuration of the spine occur early in idiopathic scoliosis and that they are associated with disturbed growth of the vertebral body but not of the posterior elements. These findings seem to reflect a simulataneous deformation in the coronal and sagittal planes rather than a single growth disturbance in any specific plane.
Load affects remodeling of transplanted, autogenous bone‐patellar tendon‐bone segments in a rabbit model
Authors: Muneta Takeshi , Lewis Jack L. , Stewart Nathaniel J.
Published: February 2005

The question of whether or not load affects the remodeling of a transplanted autogenous free graft was addressed by removal of the patella‐patellar tendon‐tibial tubercle complex from the right knees of 15 New Zealand White rabbits. The tubercle was split, and the tendon was divided with each half trimmed to an equal width. The autograft complex was transplanted into a subcutaneous tunnel on the back of the rabbit. Controlled cyclic loads were applied via transcutaneous sutures to half of the graft, while the other half remained unloaded. The mechanical stiffness and strength and the cell density of loaded and unloaded halves of the autograft were measured in nine animals at 3 weeks and in six animals at 6 weeks. Five autografts from four additional rabbits served as unimplanted controls. An analysis of variance showed that the loaded portions of the autografts had a significantly higher failure strength (mean of 90%) and were significantly stiffer (mean of 62%) than the unloaded halves at 3 and 6 weeks. Failure strength was significantly greater (mean of 90%) at 3 weeks than at 6 weeks. The autografts were less stiff and had a lower failure strength than the unimplanted controls, with the greatest difference occurring in the unloaded segments at 6 weeks. Histology revealed that both loaded and unloaded segments demonstrated an increase in cellularity at 6 weeks compared with 3 weeks. This report introduces a model for the study of the effect of load on soft‐tissue grafts and demonstrates that loading affects the remodeling process of a transferred autograft.
Effect of animal age and chronicity of interleukin‐1 exposure on cartilage proteoglycan depletion in vivo
Authors: Arner Elizabeth C.
Published: February 2005

Rheumatoid arthritis and osteoarthritis are characterized by an early depletion of cartilage proteoglycans, which leads to a decrease in cartilage compressibility and, eventually, to a loss of joint function. Interleukin‐1, which is thought to have a role in mediating this loss of proteoglycans in arthritis, induces an acute depletion of proteoglycans from articular cartilage following intra‐articular injection in rabbits. As the structure and metabolism of proteoglycans are known to change with age, my laboratory investigated the effect of age on depletion and recovery of proteoglycans in response to interleukin‐1 in the rabbit. Loss of cartilage proteoglycans induced by interleukin‐1 was less servere in immature animals, increased until the age of sexual maturity, and then remained constant. The rate of recovery and compensatory overshoot in the rate of proteoglycan synthesis following challenge with interleukin‐1 was more rapid in immature animals and may have been responsible for the quicker return of the cartilage proteoglycan content to control levels in younger animals. With multiple exposures to interleukin‐1 at time intervals too short for recovery to occur, smaller amounts of interleukin‐1 induced loss of proteoglycans, and the proteoglycan content and the rate of synthesis remained depressed longer after treatment had stopped. The decreased ability of mature cartilage to replace proteoglycans rapidly after exposure to cytokines would increase the probability of subsequent inflammatory episodes before recovery is complete; this may result in increased susceptibility of adult cartilage to proteoglycan depletion.
Comparative study of the intrinsic mechanical properties of the human acetabular and femoral head cartilage
Authors: Athanasiou K. A. , Agarwal A. , Dzida F. J.
Published: February 2005

Biphasic creep indentation methodology and an automated indentation apparatus were used to measure the aggregate modulus, Poisson's ratio, permeability, thickness, creep and recovery equilibrium times, and percentage of recovery of normal articular cartilage in 10 human hip joints. These properties were mapped regionally to examine the mechanical factors involved in the development of site‐specific degenerative lesions in the acetabulum and femoral head. The results indicate that there are significant differences between these properties regionally in the acetabulum and femoral head and between the two anatomical structures. Specifically, it was found that cartilage in the superomedial aspect of the femoral head has a 41% larger aggregate modulus than its anatomically corresponding articulating surface in the acetabulum. In addition, the supermedial aspect of the femoral head has the greates aggregate modulus (1.816 MPa) within the hip joint. During sitting, the inferior portion of the femoral head is in contact with the anterior acetabulum, and the anterior acetabulum has a 53% greater aggregate modulus than the inferior femoral head. This area below the fovea on the femoral head has the least aggregate modulus (0.814 MPa) within the hip joint. These mismatches in the compressive modulus of opposing articulating surfaces may contribute to degeneration of cartilage in the superomedial acetabulum and the inferior femoral head. Our findings support the clinical observation that these areas are frequent sites of early degeneration.
Characterization of extracellular matrix macromolecules from bovine synovial capsule
Authors: Kleftogiannis Fotini , Handley Christopher J. , Campbell Margaret A.
Published: February 2005

Synovial capsule from the metacarpophalangeal joints of cattle was shown to be a highly collagenous tissue, with a hydroxyproline content of 100 ± 1 μg/mg dry weight and a water content of 70 ± 3.6%. Type‐I collagen made up 83% of the collagen present, and the remainder was type III. When incubated in explant culture, synovial capsule incorporated [3H]acetate into both glycoproteins and hyaluronan and [3H]acetate and [35S]sulfate into proteoglycans. The rate of synthesis of proteoglycans by synovial tissue was shown to be similar to that measured for collateral ligament from the same joint. Two populations of proteoglycans were observed to be synthesized by synovial capsule. More than 90% of the 35S‐labelled proteoglycans eluted with a Kav of 0.7 on Sepharose CL‐4B, and the remainder of the radiolabelled macromolecules eluted from the column with a Kav of less than 0.5. Analysis of the major population of proteoglycans showed it to consist of a dermatan sulfate‐containing proteoglycan with a core protein of 45,000 Da that had the same N‐terminal amino acid sequence as decorin.
Differential levels of synovial fluid aggrecan aggregate components in experimental osteoarthritis and joint disuse
Authors: Ratcliffe Anthony , Beauvais Paul J. , Saed‐Nejad Fatemeh
Published: February 2005

The levels of proteoglycan aggregate components (link protein, keratan sulfate epitope, and total sulfated glycosaminoglycan) were determined in the synovial fluid lavages of dogs with experimental osteoarthritis or disuse atrophy. A model of experimental osteoarthritis was created by transection of the anterior cruciate ligament of the right knee; studies were carried out 6 and 12 weeks after surgery. Joint disuse was studied at 4 and 8 weeks after initiation of the disuse. Recovery after disuse also was studied in joints that had 3 weeks of remobilization after 4 or 8 weeks of disuse. Synovial fluid lavages from the right knee joints of untreated animals were used as controls. The concentrations of keratan sulfate epitope, sulfated glycosaminoglycan, and link protein in the synovial fluid lavages at 6 and 12 weeks after transection of the anterior cruciate were elevated compared with the control values. Similar analysis of the fluid after disuse showed that the levels of keratan sulfate epitope and sulfated glycosaminoglycan were increased compared with the control levels and the levels after transection. However, the concentration of link protein in the fluid after disuse was not significantly different from the control level. The levels of keratan sulfate epitope and sulfated glycosaminoglycan in the synovial fluid lavages after disuse with recovery were high, but the levels of link protein remained low. The results indicate that the catabolism of proteoglycan aggregates in articular cartilage during early osteoarthritis and disuse is different. The determination of keratan sulfate epitope in synovial fluid lavages appears to provide a relatively general indication of proteoglycan catabolism, whereas increased levels of link protein may be more indicative of cartilage degeneration.
Fit of the uncemented femoral component and the use of cement influence the strain transfer to the femoral cortex
Authors: Jasty Murali , O'Connor Daniel O. , Henshaw Robert M. , Harrigan Timothy P. , Harris William H.
Published: February 2005

To determine whether the strain patterns produced in the femoral cortex after uncemented femoral arthroplasty are influenced by the fit of the component and whether these patterns are different from those of cemented components, cortical surface strains of cadaveric femurs subjected to loads simulating single‐limb stance were measured before and after the insertion of uncemented, collared, straight‐stemmed femoral components. The effects of press fit, loose fit, and precise fit of the components were evaluated and were contrasted to the strain patterns occurring after insertion of cemented femoral components. Strains varied markedly, depending on the fit of the stem of the uncemented femoral component within the isthmus. Nearly normal patterns of femoral strain were produced when the femoral stem was fit precisely at the isthmus, and the proximal femoral strains were similar to those of the intact state. In contrast, press fit and loose fit at the isthmus altered the strain patterns. The proximal medial axial strains were significantly reduced with press fit, to a mean of 39% of normal (p < 0.05), and increased with loose fit, to a mean of 141% of normal (p < 0.05). The prostheses fixed with cement showed a mean reduction in proximal medial axial strains to 33% of normal, which was comparable with press fit uncemented components even though the collar was well seated. Thus, our findings indicated that, in the immediate postoperative period, femoral strain patterns can be influenced by the fit of an uncemented component within the isthmus and by the use of cement.
Effects of intermittent administration of pamidronate on the mechanical properties of canine cortical and trabecular bone
Authors: Acito A. J. , Kasra M. , Lee J. M. , Grynpas M. D.
Published: February 2005

The mechanical properties of cortical and trabecular bones from beagles treated with the bisphosphonate pamidronate (administered intermittently 1 week every month for 3 months, at a dosage of 0.45 μmol/kg/day) were assessed. The mechanical properties of cortical bone were measured by four‐point bending tests on femoral quadrants, in order to measure their elastic modulus and ultimate stress. The structural properties of whole tibias were measured in torsion to determine the torsional stiffness and failure torque. The elastic modulus and maximum compressive stress of the trabecular bone samples were measured by compression tests of trabecular cores. Intermittent treatment with pamidronate did not change the pattern of mechanical properties that occurs naturally around the femur or the torsional stiffness and failure torque of the tibias. By contrast, pamidronate did significantly increase the modulus of elasticity (by 19%) and maximum compressive stress (by 33%) of vertically aligned cylindrical trabecular specimens taken from the vertebrae of the beagles.
Three‐dimensional knee joint movements during a step‐up: Evaluation after anterior cruciate ligament rupture
Authors: Jonsson Håkan , Kärrholm Johan
Published: February 2005

The three‐dimensional motions of the knee were analysed during closed kinetic chain knee extension in 13 patients with unilateral chronic injury of the anterior cruciate ligament. The patients ascended a platform, and serial stereophotogrammetric roentgenograms were exposed from about 100° of flexion to full extension. From a position of about 100° of knee flexion and 20° of internal rotation, the tibia rotated externally during the extension. Almost no tibial adduction or abduction was observed. The tibial intercondylar eminence translated laterally, distally, and anteriorly relative to the femur. In knees with absence of the anterior cruciate ligament, the intercondylar eminence had a more posterior position compared with the contralateral normal knees. The proximal tibia was used as a fixed reference segment to evaluate the anteroposterior translations of a central point in the femoral condyles. The femoral point was more anteriorly displaced in the injured than in the contralateral knees. This difference might reflect increased activity of the hamstrings in the injured knees, because it was most pronounced at 80° of flexion and decreased with increasing extension. In the sagittal plane, the mean helical axis was positioned close to the femoral insertion of the ligament at 80° of flexion and was displaced distally and anteriorly during extension. In the frontal plane, the axis had a transverse direction at 80° of flexion. At close to full extension, the axis was positioned distally in the lateral condyle and proximally in the medial condyle. In the horizontal plane, the helical axes ran slightly more anteriorly in the medial than in the lateral femoral condyle but changed inclination at close to full extension and became almost parallel to the transverse axis.
Tendons attached to prostheses by tendon‐bone block fixation: An experimental study in dogs
Authors: Gottsauner‐Wolf Florian , Egger Erick L. , Schultz Fredrick M. , Sim Franklin H. , Chao Edmund Y. S.
Published: February 2005

To develop a method of tendon attachment to a metallic endoprosthesis, we evaluated fixation strength, clinical function of the tendon, and morphological changes in an experimental model. The canine supraspinatus tendon was removed from the greater tubercle of the humerus and attached to a titanium prosthesis. In 12 animals, the bone block underlying the tendon insertion was preserved and attached in one limb; the soft part of the tendon was attached directly to the prosthesis in the contralateral limb. Fixation strength was evaluated after 16 weeks of in vivo implantation (12 specimens) and compared with the in vitro fixation strength (12 specimens) and with intact normal controls (six specimens from cadavera). Function of the tendon in vivo was evaluated by force‐plate analysis (at 3‐weeks intervals). All specimens were evaluated histologically. Sixteen weeks after surgery, the tendon‐bone block attachment was significantly stronger (mean, 16%) than the direct tendon attachment and not significantly different from the normal control, and the direct tendon attachment was significantly weaker (mean, 68%) than the normal control. There was significantly more weight‐bearing on the limbs with a tendon‐bone block attachment than on the limbs with a direct tendon attachment at both 3 and 6 weeks postoperatively. Both front legs showed increased weight‐bearing with time, but the differences were not statistically significantly. Anchorage by tissue ingrowth to the titanium prosthesis was found consistently–there was bone ingrowth in the tendon‐bone block attachments and fibrous tissue ingrowth in the direct tendon attachments. When a bone block was preserved, the strength and stiffness were comparable with those of a normal tendon insertion. This mechanical linkage was capable of transmitting muscle forces to the prosthesis and consequently to the limb.
Femoral abnormalities and vitamin D metabolism in X‐linked hypophosphatemic (Hyp and Gy) mice
Authors: Meyer Ralph A. , Meyer Martha H. , Gray Richard W. , Bruns M. Elizabeth
Published: February 2005

X‐linked hypophosphatemia is a genetic bone disease in humans and mice. Two closely linked mutations in mice. Hyp and Gy. cause low plasma phosphate and a rachitic and osteomalacic bone disease. Because of the controversy as to whether Gy is a good model for X‐linked hypophosphatemia, the phenotypic severity of these two mutations was compared in both sexes and on two genetic backgrounds. The depression in plasma levels of phosphate was similar in all 10‐week‐old mutant mice. Male Hyp mice and heterozygous female Hyp mice were affected with similar severity in terms of reduced tail growth, shortened femora, reduced femoral mineral content, and abnormal mineral composition of the femoral matrix. In contrast, male Gy mice did not survive on the C57BL/6J background and were more severely affected than female Gy mice on the B6C3H background. The hybrid B6C3H background ameliorated the bone disease compared with the inbred C57BL/6J background for both mutant strains. There was no evidence of change in the plasma levels of 1.25‐dihydroxyvitamin D, duodenal level of vitamin D‐dependent calcium‐binding protein, or urinary level of calcium in these adult mutant mice. In summary, Gy mice have a sexual dimorphism not present in Hyp mice. These two genes may indicate the presence of multiple gene loci in the human disease, with multiple proteins involved in the pathophysiology of the bone disease.
Changes of cytoskeletal architecture and incorporation of 3H‐proline in contracted anterior cruciate ligament
Authors: Sonoda Masaki , Moriya Hideshige , Wada Yuichi , Shimada Yutaka
Published: February 2005

Changes of cytoskeletal architecture and incorporation of 3H‐proline were investigated in contracted anterior cruciate ligaments with use of a model of contracture. In control ligaments, fibroblasts were shown by immunofluorescence microscopy to contain actin, vimentin, and myosin in their cytoplasm. Cytoskeletons were visualized by electron microscopy as a mesh network of microfilaments among cell organelles. In contracted anterior cruciate ligaments, fibroblasts were spindle‐shaped and their cytoplasm could not be observed clearly in sections stained with hematoxylin and eosin. Actin staining was distributed irregularly and extensively, whereas vimentin and myosin staining was not scattered so extensively. When compared electromyographically, the actin staining appeared in cytoplasmic pseudopods of the fibroblasts. It was thought that these cytoplasmic pseudopods contained mainly actin and little or no other cytoskeletal elements such as vimentin and myosin. In autoradiographs, contracted anterior cruciate ligaments were shown, with use of 3H‐proline, to experience a decrease in the number of labeled cells. On the basis of these findings of cytoskeletal rearrangement and of decreased incorporation of 3H‐proline, we hypothesized that fibroblasts of the anterior cruciate ligament had the capacity to change their character during knee immobilization and to play a role in ligament contracture.
Histomorphometric analysis of innervation of the anterior cruciate ligament in osteoarthritis
Authors: Amir Gail , Lowe Joseph , Finsterbush Alex
Published: February 2005

The aim of this study was to determine whether there are quantitative changes in the innervation of the anterior cruciate ligament in osteoarthritis. Eleven whole anterior cruciate ligaments were obtained at autopsy from cadavera of individuals with advanced osteoarthritis; five healthy ligaments were used as controls. The ligaments were transected and stained with hematoxylin and eosin, oil red O for fat, and a modification of Gairn's gold chloride method. The latter stain permits visualization of axons, mechanoreceptors, and free nerve endings that are not apparent on routine stains. The ratio of nerve tissue to periligamentous synovial tissue was determined histomorphometrically by the point‐counting method. The nerve tissue was located almost exclusively in the periligamentous synovial tissue. There was a statistically significantly greater area of nerve tissue (as a percentage of the total area) around the anterior cruciate ligaments in the osteoarthritic group than around the ligaments in the control group (p < 0.02). The nerve tissue was distributed evenly throughout the periligamentous synovial tissue in the specimens in both groups. A neurological role has been proposed for the anterior cruciate ligament in osteoarthritis. This study provides morphological evidence for neural pathology of the anterior cruciate ligament in subjects with osteoarthritis.
Cyclic compressive loading results in fatigue cracks in ultra high molecular weight polyethylene
Authors: Pruitt L. , Koo J. , Rimnac C. M. , Suresh S. , Wright T. M.
Published: February 2005

Wear damage to the articulating surfaces of total joint components made of ultra high molecular weight polyethylene is associated with a fatigue fracture mechanism, despite the fact that these surfaces are subjected to primarily compressive and compressive‐tensile cyclic stresses. The question arises as to whether fatigue cracks will form under such loading conditions. In this study, we experimentally demonstrated that fatigue cracks could be initiated and propagated in notched ultra high molecular weight polyethylene specimens subjected to fully compressive and compressive‐tensile cyclic loading. Under these loading conditions, growth of fatigue cracks was limited: the cracks arrested without catastrophic failure of the test specimens. The final length of the crack was dependent on the load ratio of the fatigue cycle; fatigue cracks propagated to greater lengths as the load ratio was increased.
Hamstrings and gastrocnemius co‐contraction protects the anterior cruciate ligament against failure: An in vivo study in the rat
Authors: Aune Arne Kristian , Nordsletten Lars , Skjeldal Sigmund , Madsen Jan Erik , Ekeland Arne
Published: February 2005

An anesthetized rat model was used to study the effects of muscle contraction on the ultimate tensile load and the energy absorption at failure of the anterior cruciate ligament. In both knees, the joint capsule and ligaments, except for the anterior cruciate ligament, were divided, and the menisci were removed with the aid of a stereomicroscope. The cruciate ligament of the right knee was tested in tension until failure by femorotibial distraction during contraction of the hamstrings and calf muscles induced by electrical stimulation of the ischiatic nerve. The cruciate ligament of the left knee, which was loaded to failure with nonstimulated (relaxed) muscles, served as the control. The mean ultimate tensile load during muscle contraction was 86 N compared with 53 N when tested with relaxed muscles (p < 0.001). The energy absorption at failure was 0.41 and 0.19 J during contraction and relaxation, respectively (p < 0.05). This study suggests that previous investigations evaluating the force and energy necessary to rupture the anterior cruciate ligament (with use of a femur‐anterior cruciate ligament‐tibia complex stripped of all soft tissues and without gastrocnemius‐hamstring muscle contractions) are incomplete and probably not representative of the in vivo situation.
Adhesiveness of human ligament fibroblasts to laminin
Authors: Sung K‐L. Paul , Steele Laura L. , Whittermore Darren , Hagan Jay , Akeson Wayne H.
Published: February 2005

The adhesiveness of fibroblasts from the human anterior cruciate and medial collateral ligaments to the laminin molecule was studied, with particular emphasis on the intrinsic differences between fibroblasts from the two ligaments. Cellular adhesion strength, adhesion area, laminin concentration, and seeding time were examined. Cell adhesion to laminin anchored with poly‐D‐lysine to a cleaned cover glass was measured with a micropipette micromanipulation system after seeding. The adhesion strength of fibroblasts from the anterior cruciate ligament to laminin was greater than and significantly different from that of fibroblasts from the medial collateral ligament, depending on the laminin concentration. Fibroblasts from the anterior cruciate ligament also exhibited an increase in adhesion strength, dependent on laminin concentration of as much as 30 μg/ml, at which the laminin receptors were thought to be saturated. Fibroblasts from the medial collateral ligament did not show such an increase except at laminin concentrations of 5–10 μg/ml. There was no significant difference in adhesion area between fibroblasts from the two ligaments except after 45 minutes at a laminin concentration of 40 μg/ml. For both, the adhesion to laminin showed little correlation to seeding time during periods of as long as 60 minutes. Measurements of adhesion area also failed to show a significant correlation to seeding time for fibroblasts from either ligament at laminin concentrations of 20 and 40 μg/ml. Adhesion strength normalized by adhesion area had no correlation to seeding time. With all times taken into account, however, normalized adhesion strength for fibroblasts from the anterior cruciate ligament was approximately two times greater than and significantly different from that for fibroblasts from the medial collateral ligament at laminin concentrations of 20 and 40 μg/ml. Fibroblasts from the anterior cruciate ligament adhere more strongly to laminin than do those from the medial collateral ligament. This study may prove useful in the understanding of fibroblast adhesion to the basal lamina within the extracellular matrix and may provide insight into the natural healing processes of the anterior cruciate and medial collateral ligaments.
Immobilization of the knee joint alters the mechanical and ultrastructural properties of the rabbit anterior cruciate ligament
Authors: Newton Peter O. , Woo Savio L‐Y. , MacKenna Deidre A. , Akeson Wayne H.
Published: February 2005

The effects of immobilization of the knee joint on the mechanical and ultrastructural properties of the anterior cruciate ligament have not been well documented. Our goal was to determine these effects in a rabbit model and to assess the effect of knee flexion angle during immobilization. The knee joint was immobilized in either 170° or 105° of flexion, and new methodologies were utilized to determine the mechanical properties of the anterior cruciate ligament. In specimens from knees that had been immobilized, the cross‐sectional area of the ligament was 74% of the control value. The stress‐strain curve was altered slightly, and the strain at failure increased 32–40%. The modulus and stress at failure did not decrease significantly. There was no significant difference between the mechanical properties of the knees immobilized at 170° and 105° of flexion. Histological and ultrastructural evaluation demonstrated changes in the shape and intracellular makeup of the fibroblasts from the ligament after immobilization. This cellular response may account for the alterations in the mechanical properties of the anterior cruciate ligament.
Reduction of patellofemoral contact forces following anterior displacement of the tibial tubercle
Authors: Singerman Robert , White Craig , Davy Dwight T.
Published: February 2005

Retropatellar pain often accompanies malalignment syndromes and frequently is attributed to excessive patellofemoral contact stresses. Elevation (anterior displacement) of the tibial tubercle has been recommended to relieve these conditions. The degree to which patellar contact forces are decreased and the extent to which elevation alters medial‐lateral forces have not been studied directly. We performed anterior translation of the tibial tubercle in knees from cadavers and measured the effect on the magnitude of the three‐dimensional patellofemoral contact force with use of a specially designed 6‐degrees‐of‐freedom force transducer, with the natural patellar articular surface in place. Measurements were made in nine knees (average age 67 years, range 46–92 years). The resultant contact force decreased linearly with increasing tubercle elevations of as much as 2.5 cm. The average reduction per centimeter of elevation was 17% of the force measured with no elevation. Elevation of the tubercle had an inconsistent effect on the medial‐lateral component of the contact force. As the elevation was increased, six knees exhibited an increase in the medial‐lateral component of the contact force acting medially on the knee and three knees exhibited a decrease in this force component. The results of this study show that, while elevation of the tubercle without medialization reduced the total contact force on the patella, the medial‐lateral component of this force was altered it an unpredictable way.
Mathematical model for repair of fatigue damage and stress fracture in osteonal bone
Authors: Martin Bruce
Published: February 2005

This paper assembles current concepts about bone fatigue and osteonal remodeling into a mathematical theory of the repair of fatigue damage and the etiology of stress fracture. The model was used to address three questions. (a) How does the half‐life of fatigue damage compare with the duration of the remodeling cycle? (b) Does the porosity associated with the remodeling response contribute to stress fracture? (c) To what extent is a periosteal callus response necessary to augment repair by remodeling? To develop the theory, existing experimental data were used to formulate mathematical relationships between loading, damage, periosteal bone formation, osteonal remodeling, porosity, and elastic modulus. The resulting nonlinear relationships were numerically solved in an iterative fashion using a computer, and the behavior of the model was studied for various loading conditions and values of system parameters. The model adapted to increased loading by increasing remodeling to repair the additional damage and by adding new bone periosteally to reduce strain. However, if too much loading was encountered, the porosity associated with increased remodeling caused the system to become unstable: i.e., damage, porosity, and strain increased at a very high rate and without limit. It is proposed that this phenomenon is the equivalent of a stress fracture and that its biological and mechanical elements are significant in the etiology of stress fractures. Additional experiments must be done to test the model and provide better values for its parameters. However, the instability characteristic is relatively insensitive to changes in model parameters.
Modulation of cell phenotype in human osteoblast‐like cells by the simian virus 40
Authors: Evans Carol E. , Ng Kin , Allen Justine , Gallimore Phillip
Published: February 2005

At present, the majority of in vitro research into bone metabolism is performed on either primary cultures of bone or osteosarcoma lines. A better model of the behaviour of normal bone cells would be a cell line derived from normal, adult bone that retained osteoblast‐like characteristics. We infected a culture of bone cells from adult humans with simian virus 1613, a variant of the simian virus 40, and obtained 12 clones of variable morphology. The clones were maintained in culture for as long as 6 months. Population doubling times, synthesis of alkaline phosphatase and osteocalcin, secretion of mineral, morphology, and ability to withstand freezing were examined. SV/EC cell morphology varied from the polygonal, osteoblast‐like to the bipolar, fibroblast‐like. Population doubling times ranged from 0.55 to 2.8 days (compared with 3.9 days for the nontransformed human osteoblast‐like cells). Synthesis of alkaline phosphatase varied but was less than that by the human osteoblast‐like cells. With the exception of clone 11, all of the transformed clones synthesised mineral in vitro under mineralising conditions. Four clones showed increased synthesis of alkaline phosphatase and increased population doubling times after passaging. All of the clones were successfully frozen and thawed, but, unlike normal human osteoblast‐like cells, none responded to stimulation with parathyroid hormone. These results demonstrate that normal human bone cells can incorporate the simian virus 1613 while retaining some of their osteoblast‐like characteristics. Such manipulation affords these cells an extended lifespan, and this, together with their ability to withstand freezing, makes them a potentially useful tool in bone research.
Polymethylmethacrylate‐stimulated macrophages increase rat osteoclast precursor recruitment through their effect on osteoblasts in vitro
Authors: Pollice P. F. , Silverton S. F. , Horowitz S. M.
Published: February 2005

An in vitro rat osteoclast precursor model was employed to study the role of macrophages in the osteolysis associated with aseptic loosening of cemented total joint replacements. Bone resorption at the bone‐bone cement interface may involve the release of mediators by macrophages in response to phagocytosis of polymethylmethacrylate particles. Two potential pathways for the macrophage‐directed bone resorption were studied. An indirect pathway was investigated in which the macrophage response to cement particles was used to stimulate rat osteosarcoma (ROS) 17/2.8 osteoblasts. Osteoblast‐soluble factors then were added to osteoclast precursors. In the direct pathway, osteoclast precursors were exposed directly to macrophage‐soluble factors released in response to phagocytosis of cement particles. Osteoclast precursors were identified after adherence to polished human dentin slices. Acid phosphatase‐positive osteoclasts were counted using light microscopy at ×200 magnification. In the indirect pathway, where the macrophage response was mediated through the rat osteosarcoma osteoblasts, a significant increase in the recruitment of osteoclast precursors was observed. In the direct pathway, when the macrophage‐conditioned medium was allowed to interact directly with osteoclast precursors, the adherence of the precursors was significantly decreased. This demonstrates that the macrophage mediators released following phagocytosis of polymethylmethacrylate particles affect the release of soluble factors from osteoblasts. In turn, these osteoblast factors stimulate recruitment of osteoclast precursors to calcified tissue. Evidence from this in vitro model reveals that macrophage‐soluble factors, in the absence of an osteoblast contribution, decrease the adherence of osteoclast precursors to calcified substrate. We propose that bone resorption at the aseptically loose interface of cemented arthroplasty may be mediated, at least in part, by soluble factors secreted by osteoblasts responding to macrophages that have phagocytosed particles of polymethylmethacrylate cement.
Comparison of the effect of reamed and unreamed locked intramedullary nailing on blood flow in the callus and strength of union following fracture of the sheep tibia
Authors: Schemitsch E. H. , Kowalski M. J. , Swiontkowski M. F. , Harrington R. M.
Published: February 2005

This study was performed to compare the effects of reamed and unreamed locked intramedullary nailing on blood flow in the callus and early strength of union in a fractured sheep tibia model. After the creation of a standardized short spiral fracture by three‐point bending with torsion, each tibia was stabilized by the insertion of a locked intramedullary nail. Ten animals were allocated randomly into two groups: one that had reaming prior to nail insertion and one that did not. Blood flow was measured in real time with use of laser Doppler flowmetry. Endosteal perfusion was determined at the fracture site before and after nail insertion. Perfusion of the callus was measured at three locations (proximal diaphysis, fracture site, and distal diaphysis) and at three time intervals (2, 6, and 12 week follow‐up). All animals were killed 12 weeks postoperatively, and the tibiae were tested to failure in four‐point bending. Nailing with reaming resulted in a larger decrease in overall endosteal perfusion than nailing without reaming (p < 0.015). The presence or absence of reaming did not affect blood flow within fracture callus. Perfusion of callus was greatest at 6 weeks of follow‐up. Bending strength and stiffness were the same in both groups at 12 weeks. The study demonstrated that perfusion of callus and early strength of union are similar following intramedullary nailing with or without reaming.
Synergistic effect of growth factors on cell outgrowth from explants of rabbit anterior cruciate and medial collateral ligaments
Authors: Lee Joe , Green Melvin H. , Amiel David
Published: February 2005

Cellular migration and proliferation are integral aspects of wound healing. An in vitro assay for cellular migration and proliferation using explants of rabbit anterior cruciate and medial collateral ligaments was developed previously. This study presents the effects of serum‐free culture medium supplemented with basic fibroblast growth factor, bovine insulin, transforming growth factor‐β1, and platelet‐derived growth factor‐B, added either individually or in combination, on cell outgrowth in explants of rabbit anterior cruciate and medial collateral ligaments. Outgrowth was assessed at 3 and 6 days by counting the number of cells surrounding the tissue explants. For explants of both ligaments, cell outgrowth was dependent on the presence of 10% fetal bovine serum or the combination of growth factors. Little outgrowth occurred in explants of either ligament in the presence of basic fibroblast growth factor, transforming growth factor‐β1, or bovine insulin. Platelet‐derived growth factor‐B at concentrations of 20 and 100 ng/ml seemed to increase cell outgrowth from medial collateral ligament explants at 6 days. The outgrowth from the explants of both ligaments was much greater in the presence of all four growth factors than the sum of the outgrowth with the individual factors. This synergistic effect was as much as 10‐fold and 20‐fold for the anterior cruciate ligament explants at days 3 and 6, respectively, but no more than 3‐fold for the medial collateral ligament explants at these times. Medial collateral ligament explants exhibited greater cell outgrowth than anterior cruciate ligament explants in 10% serum and in the presence of the four growth factors.
Mechanical behavior of articular cartilage in shear is altered by transection of the anterior cruciate ligament
Authors: Setton L. A. , Mow V. C. , Howell D. S.
Published: February 2005

The flow‐independent viscoelastic and equilibrium behaviors of canine articular cartilage were examined with time after transection of the anterior cruciate ligament. The equilibrium, transient, and dynamic shear behaviors of cartilage were studied in biaxial compression‐torsion testing at two time periods after transection of the anterior cruciate ligament and at two sites on the femoral condyle, in order to test for differences between sites of frequent and less frequent contact. Water content also was measured in cartilage at sites corresponding to the areas of mechanical testing. Transection of the anterior cruciate ligament produced significant decreases in all measured moduli of articular cartilage tested in equilibrium and dynamic shear and in equilibrium compression; the values for these moduli were 61, 56, and 77% of the control values, respectively, beginning at 6 weeks following transection of the anterior cruciate ligament. There was evidence of increased energy dissipation of cartilage in shear, with a 13 and 35% increase in tan δ at 6 and 12 weeks after transection of the anterior cruciate ligament, respectively. Changes in the viscoelastic relaxation function of cartilage in shear also were evident at 12 weeks after surgery. In all tissue, there was a significant increase in hydration of approximately 4% at 6 or 12 weeks after surgery. There was little difference between the material parameters for areas considered to be in frequent and less frequent contact, with the exception of hydration, which was greater for areas of less frequent contact. The observed changes in material properties demonstrate that relatively short periods of joint instability result in significant changes in the flow‐independent viscoelastic behavior of articular cartilage, as well as in the intrinsic stiffnesses in compression and shear.
Effects of excimer laser on healing of articular cartilage in rabbits
Authors: Athanasiou K. A. , Fischer R. , Niederauer G. G. , Puhl W.
Published: February 2005

This study examined healing of 1.0 mm diameter defects in rabbit knee articular cartilage for as long as 14 weeks after creation of the defects by either laser or drilling. The purpose of the research was to determine the effects of laser debridement of cartilage on the intrinsic biomechanical properties of the repair tissue. We therefore imitated chondral shaving and subchondral abrasion of cartilage by creating partial‐thickness and full‐thickness cartilage defects of standardized size with both excimer laser and drilling. Light and scanning electron microscopic examinations of the repair tissue showed that healing of osteochondral defects created by laser may be delayed compared with defects created by drilling, for at least 6 weeks postoperatively. Even though there initially was a considerable delay in healing in the laser group, neither laser nor drilling had any appreciable effects on the mechanical properties of the repair tissue, as demonstrated by biomechanical testing at 14 weeks. Specifically, the repair cartilage in the defects in the laser group had the following material properties (mean ± SD): aggregate modulus, 0.40 ± 0.24 MPa; Poisson's ratio, 0.37 ± 0.08; permeability, 3.72 ± 4.28 × 10−15 m4/N.s; and thickness, 0.20 ± 0.06 mm. The corresponding values for the defects in the drilling group were 0.39 ± 0.23 MPa, 0.34 ± 0.09, 3.82 ± 3.44 × 10−15 m4/N.s, and 0.22 ± 0.09 mm. The repair tissue from both types of defects was pooled, and the values were compared with those for contralateral (control) tissue. The control tissue had a 51% greater aggregate modulus (0.59 ± 0.18 MPa, p = 0.0001), 34% less Poisson's ration (0.23 ± 0.25, p = 0.0001), 48% less permeability (1.94 ± 0.96 × 10−15 m4/N.s, p = 0.0001), and was 29% thicker (0.27 ± 0.08 mm, p = 0.0001). Thus, as evidenced by biomechanical testing at 14 weeks, neocartilage in both superficial and osteochondral defects, created by either laser or a drill, exhibited structural integrity inferior to that of normal control tissue.