bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanics of patellar tendon autograft for reconstruction of the anterior cruciate ligament in the goat: Three‐year study
Authors: Ng Gabriel Y. , Oakes Barry W. , Deacon Owen W. , McLean Iain D. , Lampard Douglas
Published: February 2005

This study examined the biomechanics of anterior cruciate ligament‐patellar tendon autografts for as long as 3 years after surgery. Twenty‐seven adult female goats were tested; four served as controls and the others received an autograft to the right knee with each left knee serving as an additional control. The animals with grafts were tested at 0 week (n = 4), 6 weeks (n = 4), 12 weeks (n = 4), 24 weeks (n = 3), 1 year (n = 5), and 3 years (n = 3) after surgery. The anteroposterior laxity of the knee joint, load‐relaxation, and structural and material properties of the graft were tested. The anteroposterior laxity was significantly greater than that of the controls for all groups except at 3 years. Load‐relaxation was greater than that of the control anterior cruciate ligaments, but in the 1 and 3‐year grafts load‐relaxation was less than that of the patellar tendons with 5 minutes of sustained loading. Between 12 and 52 weeks, the stiffness and modulus of the grafts increased 3‐fold, but the improvement was slow afterward. At 3 years, the strength and stiffness of the grafts were 44 and 49% those of the control ligaments, respectively; the modulus was 37 and 46% that of the control anterior cruciate ligaments and patellar tendons, respectively. The persistent inferior mechanical performance at 3 years suggests that anterior cruciate ligament grafts may never attain normal strength.
Comparison of the type‐2 insulin‐like growth factor receptor in normal osteoblasts and osteosarcoma‐derived osteoblast‐like cells
Authors: Ishibe M. , Nojima T. , Ishibashi T. , Koda T. , Rosier R. N. , Puzas J. E. , Kaneda K.
Published: February 2005

Insulin‐like growth factor‐II is known to stimulate the proliferation and differentiation of osteoblasts in part through activation of the type‐2 insulin‐like growth factor receptor. The present study examined the type‐2 insulin‐like growth factor receptors of three normal osteoblast‐like cells and three osteosarcoma‐derived osteoblast‐like cells (OGA, SU, and IMAI) from humans. [125I]insulin‐like growth factor‐II was used for the binding studies. All of the cell types had high affinity binding sites for insulin‐like growth factor‐II (dissociation constants [Kd] ⩽ 1 nM). The concentration of these sites was 10 to 24‐fold higher in normal osteoblasts than in the osteosarcoma cells studied. Unlabeled insulin‐like growth factor‐II inhibited the binding of [125I]insulin‐like growth factor‐II to the cells in a dose‐dependent manner; however, unlabeled insulin‐like growth factor‐I and insulin were less effective. Covalent crosslinking of insulin‐like growth factor‐II binding sites gave molecular mass estimates of Mr 250,000 in human osteoblast cells, 250,000 and 130,000 in OGA cells. 240,000 in SU cells, and 250,000 and 130,000 in IMAI cells. Unlabeled insulin‐like growth factor‐II inhibited all affinity labeling. In Northern blot analysis, the type‐2 insulin‐like growth factor receptor mRNA of normal osteoblasts was seen in greater abundance than it was in osteosarcoma cells. These results indicate that the numbers of type‐2 insulin‐like growth factor receptors differ between normal and transformed osteoblasts and that the differential expression of the receptor may be due to the differentiation of osteoblasts.
De novo synthesis of type‐I collagen in bone biopsy material
Authors: Röcher W. , Hostert E. , Dietz G. , Bartholmes P.
Published: February 2005

A simple and rapid method was established for the cultivation of bone cell tissue. Human bone tissue derived from orthopaedic surgery was cultivated in the presence of 14C‐proline and β‐aminopropionitrile. De novo synthesized collagen was extracted from the tissue and quantified by determination of radioactivity in the purified protein. Measurements of the oxygen consumption of the tissue provided evidence that the physiological conditions for the tissue were optimal. The tissue was vital over a period of as long as 7 days, showing normal respiration and a constant rate of collagen synthesis. The observed levels of alkaline phosphatase and acid phosphatase activity clearly demonstrated that mainly osteoblasts were involved in metabolic activity. The described system is suitable for investigations of bone cell metabolism under quasiphysiological conditions.
Involvement of platelets in stimulating osteogenic activity
Authors: Slater Michael , Patava John , Kingham Karen , Mason Rebecca S.
Published: February 2005

Osteoblast‐like cells have been shown to be sensitive to the proliferative action of a wide variety of growth factors. Many of these growth factors have been isolated from platelets and are thought to be released at local sites in response to injury. In this study, we tested whether human platelet concentrate, as a supplement to basic medium, would support the proliferative and functional activity of human fetal osteoblast‐like cells in both short‐term and long‐term culture. In short‐term studies, uptake of [3H]thymidine was increased in platelet‐treated cultures by more than 4‐fold compared with 10% serum‐supplemented controls. When cultured for prolonged periods on coverslips, the cells formed multilayers, with a collagen‐based matrix separating the layers. Long‐term cultures that were treated with 1.5% (vol/vol) platelets in serum‐supplemented medium showed increases in the depth of the multilayers of as much as 36‐fold at 30 days after confluence, compared with the 10% serum‐supplemented controls; this difference persisted until day 50. Incorporation of growth factor in the matrix was examined with the use of colloidal gold immunoelectron microscopy. Immunogold labeling intensities for transforming growth factor‐β1 were significantly lower in the platelet‐treated cultures at 20 days and then increased to a maximum level of 2.1‐fold more than in the controls at 40 days. Labeling intensities for insulin‐like growth factor‐I and basic fibroblast growth factor were significantly lower in the platelet‐treated cultures than in the controls at all stages of culture. These results indicate that platelet‐supplemented medium stimulates proliferation and maintains the differentiated function of human osteoblast‐like cells. Platelets may play an important role in early healing of fractures and also may be useful as a cheap autologous source of multiple growth factors to enhance osteoblast proliferation in vivo and in vitro.
Uniformity of resorptive bone loss induced by disuse
Authors: Gross Ted S. , Rubin Clinton T.
Published: February 2005

Strains induced in the skeleton by functional activity are critical to the homeostasis of bone tissue. An in vivo model of disues osteopenia was used to examine whether the removal of these regulatory stimuli induces a uniform loss of crotical bone through the whole organ or whether the loss of bone is focused at specific sites of the cortex. The right radii of five adult male turkeys were isolated from their normal functional loading for 8 weeks. The corresponding left radius from each animal served as an intact contralateral control. An additional group of five turkeys was used as time‐zero controls to assess the initial areal symmetry of the left and right radii. Areal properties were assessed at three sites at equal intervals spanning the middle 3 cm of the diaphysis. Adaptation was determined for each cross section as a whole, as well as specifically by site by division of each cross section into 12 equal angle sectors. The average across all experimental sections after 8 weeks of disuse was 12.1 ± 1.9% (± SE) loss of bone mass. The change in mean cross‐sectional area varied little between the three diaphyseal sites (−10.2 ± 3.3%, −13.5 ± 3.8%, and −12.6 ± 4.0%) and occurred primarily (84%) by uniform expansion of the endosteal envelope. However, elevated intracortical porosity following 8 weeks of disuse was highly nonuniform, with 58% of the increased porosity preferentially located in the ventral/caudal cortex (representing only 25% of the cortical area). From these data, it is concluded that bone responds to the removal of functional stimuli with a uniform, organ‐wide loss of mass, yet intracortical remodeling occurs preferentially within specific areas of the cortex. The lack of spatial coupling between these events suggests that the two processes may be governed by distinct physiologic criteria.
Evaluation of influence of 24‐hour cold preservation on endothelin production and on endothelin receptors in the bone vasculature
Authors: Coessens Bruno C. , Adams Mary L. , Wood Michael B.
Published: February 2005

Endothelin‐1 is a vasoactive peptide produced by the vascular endothelium. It is one of the most potent endogenous vascular smooth muscle constrictors. Two subtypes of the endothelin receptor have been cloned and sequenced and denoted endothelin‐A and endothelin‐B. The aim of this study was to define the influence of cold ischemia on the production of endothelin‐1 and on the endothelin receptors. Two different preservation techniques (cold storage only and cold storage with microperfusion with University of Wisconsin solution) also were compared. The study was performed in an in vitro bone perfusion model to isolate the vascular endothelium from blood components. The production of endothelin‐1 by the bone vasculature was not altered after 24 hours of cold ischemia. No contractions were observed with S6c, a selective endothelin‐B agonist, and this effect was not influenced by cold ischemia. The response mediated by the endothelin‐A receptor was increased significantly, an effect that was not influenced by preservation with University of Wisconsin solution. This latter finding was the only significant alteration in the vascular function detected in the in vitro model after 24 hours of cold ischemia. With regard to the pharmacologic properties of endothelin‐1, this mediated response could be implicated in the pathogenesis of vasospasm.
Human monocyte response to particulate biomaterials generated in vivo and in vitro
Authors: Shanbhag Arun S. , Jacobs Joshua J. , Black Jonathan , Galante Jorge O. , Glant Tibor T.
Published: February 2005

We studied the ability of four clinically relevant particle species to stimulate human peripheral blood monocytes to release bone‐resorbing agents, including interleukin‐1 (both interleukin‐1α and interleukin‐1β), interleukin‐6, and prostaglandin E2. The species studied were titanium‐6%aluminum‐4%vanadium (TiAlV), commercially pure titanium, fabricated ultrahigh molecular weight polyethylene, and polyethylene retrieved from interfacial membranes of failed uncemented total hip arthroplasties. For all species, the mean size was less than 1 μm. Human peripheral blood monocytes were challenged with these particles in a uniform manner on the basis of surface area. Phorbol 12‐myristate acetate, zymosan, and nonphagocytosable titanium particles served as controls. Stimulation of human monocytes is a function of the composition and concentration of particles. In this study. TiAlV particles appeared to be the most competent to elicit the synthesis and release of inflammatory mediators. Particles of commercially pure titanium and of fabricated ultrahigh molecular weight polyethylene also could induce the release of various cellular mediators, albeit at a lower level, whereas the particles of polyethylene retrieved from interfacial membranes were less stimulatory in these short‐term in vitro experiments.
Quantitation of articular cartilage using magnetic resonance imaging and three‐dimensional reconstruction
Authors: Marshall K. W. , Mikulis D. J. , Guthrie B. M.
Published: February 2005

A quadrature knee coil was used in conjunction with a magnetic resonance imaging scanner for quantitation of test phantom volumes, ex vivo bovine cartilage thickness, and in vivo human articular cartilage volumes. Optimal magnetic resonance parameters were obtained by testing a series of spin‐echo and gradient‐echo pulse sequences to determine the sequence that provided the highest resolution of articular cartilage and best defined the cartilage interfaces with synovial fluid and subchondral bone. Extensive testing revealed that two sequences were required to define articular cartilage accurately: a spoiled gradient‐echo sequence and a steady state free‐precession sequence. Three‐dimensional reconstruction and statistical analyses of test phantoms and of bovine and human cartilage images were performed. Differences between actual phantom volumes and three‐dimensional measurements demonstrated that, as magnetic resonance slice thickness was increased, the measurement variability also increased (coefficient of variation ranging from 1.7 ± 1.3% for 1.0 mm slice thickness to 22.7 ± 1.9% for 3.0 mm slice thickness). When the phantom volume was greater than 1,800 mm3, the intraobserver, interobserver and interscan accuracies were greater than 97, 98, and 96%, respectively. This high degree of reproducibility pertained for the data on in vivo human cartilage data also. For experienced observers, the intraobserver and interobserver reproducibility were greater than 98 and 97%, respectively. The interscan reproducibility was greater than 98%. These data demonstrate that improved magnetic resonance pulse sequencing, in conjunction with three‐dimensional reconstruction and measurement techniques, can accurately and reproducibly measure the volume of articular cartilage. Clinical application of this approach offers the potential for early diagnosis of osteoarthritis and for serial, noninvasive assessment of changes in articular cartilage volume in response to therapeutic modalities.
Effects of valgus tibial angulation on cartilage degeneration in the rabbit knee
Authors: Lovász György , Llinás Adolfo , Benya Paul , Bodey Béla , McKellop Harry A. , Luck James V. , Sarmiento Augusto
Published: February 2005

Thirteen adult female rabbits underwent unilateral osteotomy of the proximal tibia. In nine animals, 30° of valgus angulation was created; in four animals, osteotomy without angulation was performed. After a 12‐week survival period, the knee joints were processed for histology by staining with hematoxylin and eosin and safranin O. Additionally, the chondroitin sulphate epitopes 3‐B‐3 (−) and 7‐D‐4 were evaluated immunohistochemically as markers of osteoarthritis. Changes of the articular surface of the tibia were visualized by scanning electron microscopy. Light microscopic evaluation by the Mankin et al. scoring system revealed mild or moderate damage of the cartilage in the lateral compartment of angulated extremities when compared with the control side. Immunohistology with the monoclonal 3‐B‐3 and 7‐D‐4 antibodies showed no increased expression of these epitopes in the lateral compartments of the knee. Scanning electron microscopic evaluation of the tibial surfaces revealed slight surface damage localized to the central, weight‐bearing portion of the lateral tibial plateau of angulated extremities. Angulation of 30° led to only mild degenerative changes of the cartilage. These results indicate that, in the short term, cartilage has considerable capacity to withstand the effects caused by severe angulation of the limb.
Dose‐dependent response of gamma irradiation on mechanical properties and related biochemical composition of goat bone‐patellar tendon‐bone allografts
Authors: Salehpour A. , Butler D. L. , Proch F. S. , Schwartz H. E. , Feder S. M. , Doxey C. M. , Ratcliffe A.
Published: February 2005

We studied the effects of gamma irradiation on the dimensions, mechanical and material properties, and mature hydroxypyridinium crosslink density of collagen in goat patellar tendon‐bone specimens. Left and right patellar tendon‐bone units were removed from 10 adult female goats and were bisected longitudinally. Each tendon half was frozen, and then the left halves were exposed to 4, 6, or 8 Mrad (40,000,60,000, or 80,000 Gy) of gamma irradiation. The contralateral tendon halves served as controls (no irradiation). Each specimen then was loaded to failure in tension, and its soft‐tissue midsubstance was processed to measure collagen content and hydroxypyridinium crosslink density. Dose‐dependent reductions in the mechanical properties were found, including 46% (p < 0.01) and 18% (p < 0.05) reductions in maximum force and stiffness, respectively, at 4 Mrad. Similar reductions were noted in material properties, including 37% (p < 0.005) and 8% (p > 0.05) reductions in maximum stress and modulus, respectively, at 4 Mrad. These results are consistent with our previous report involving 2 and 3 Mrad (20,000 and 30,000 Gy) of exposure. We also found significant decreases in hydroxypyridinium crosslink density with 6 Mrad of irradiation (p < 0.05). However, since only one biomechanical parameter (modulus) correlated significantly with only one biochemical measure (hydroxypyridinium crosslink density) (p < 0.05), other possible mechanisms also are being explored to more fully explain these dose‐dependent changes.
Intraoperative graft tensioning alters viscoelastic but not failure behaviours of rabbit medial collateral ligament autografts
Authors: King Graham J. W. , Edwards Pamela , Brant Rollin F. , Shrive Nigel G. , Frank Cyril B.
Published: February 2005

The effects of three different degrees of intraoperative graft tensioning on measures of ex vivo laxity, viscoelastic behaviour, and structural and material failure of isolated healing medial collateral ligament autografts were investigated in a rabbit model. The grafts were orthotopically replaced at one of three different loads (too tight, anatomic, or too loose) and were mechanically evaluated after 0, 12, 24, and 48 weeks of healing. Laxity of the ligament was influenced by intraoperative graft tensioning at time zero. However, after 12 weeks of healing, values for laxity were indistinguishable among the experimental groups. Cyclic load relaxation, a measure of viscoelastic behaviour, was significantly influenced by intraoperative graft tensioning, and this effect persisted even after 48 weeks of healing. Grafts placed under excessive tension relaxed one‐third less than grafts placed under abnormally low in situ tension. The relevance of these differences remains to be determined. Intraoperative tensioning had no significant influence on characteristics of structural or material failure of the graft during the first year of healing. These results suggest that, in this model, control of graft tension at the time of placement and fixation does not improve the failure characteristics of the medial collateral ligament. The structural strength of the grafts collectively improved to nearly normal values after 48 weeks; however, material recovery was less complete. Failure loads averaged 89% of control values, whereas failure stress averaged only 52% after 48 weeks of healing.
Soft‐tissue “flaws” are associated with the material properties of the healing rabbit medial collateral ligament
Authors: Shrive N. , Chimich D. , Marchuk L. , Wilson J. , Brant R. , Frank C.
Published: February 2005

This study evaluated microscopic flaws in the healing rabbit medial collateral ligament and their significance in terms of the material properties of this ligament during healing. A gap injury was created in the midsubstance of the medial collateral ligament in the right hindlimb of 15 skeletally mature (12 months old) New Zealand White rabbits. At postoperative intervals of 3, 6, or 14 weeks, histomorphometric analysis of the flaws was carried out in subgroups of animals. The medial collateral ligaments from four of the left hindlimbs (randomly selected) were used as uninjured contralateral controls. In one histologic section of each area of scar tissue and the analogous area in the controls, specified tissue flaws (blood vessels, fat cells, hypercellular areas, loose matrix, disorganized matrix, or a combination of these) were measured by four independent and blinded observers. The results showed that the mean total area of the flaws, as a percentage of the total section, and the mean area of the largest flaw decreased with healing time in each healing group but did not achieve control values by 14 weeks. Because it was not possible to test the healing medial collateral ligaments mechanically prior to measurement of the flaws (due to the destructive nature of failure testing), the data on the flaws were compared with the material strength and stiffness of a separate series of similarly injured and mechanically tested medial collateral ligaments (data published previously). A maximum likelihood statistical analysis showed a very strong functional association between the mean area of the largest flaw and the stress at failure (p < 0.004) and between the mean flaw area as a percentage of the total section area and the elastic modulus (p < 0.001). This study therefore demonstrates that it is possible to quantify material flaws in scar tissue in rabbit medial collateral ligaments, that these flaws become smaller with healing time as the scar remodels, and that flaws are functionally associated with the material properties of the ligament in this model (larger flaws with less tensile strength and more flaws with less stiffness).
Expression of interleukin‐6 in osteoarthritic chondrocytes and effects of fluid‐induced shear on this expression in normal human chondrocytes in vitro
Authors: Mohtai M. , Gupta M. K. , Donlon B. , Ellison B. , Cooke J. , Gibbons G. , Schurman D. J. , Smith R. Lane
Published: February 2005

This study tested the effect of fluid‐induced shear on interleukin‐6 expression in normal human articular chondrocytes in vitro. As determined by Northern blot analysis, interleukin‐6 mRNA expression occurs in chondrocytes from osteoarthritic cartilage but not in normal chondrocytes. Applying fluid‐induced shear stress to primary high density cultures of chondrocytes increased interleukin‐6 mRNA signal 4‐fold at 1 hour and 10 to 15‐fold at 48 hours compared with unsheared control cultures. At 48 hours, fluid‐induced shear stress increased interleukin‐6 protein levels in the culture medium 9 to 10‐fold compared with unsheared controls, mRNA signals for interleukin‐1α, interleukin‐1β, and tumor necrosis factor‐α in RNA from sheared or control chondrocytes were not detected by Northern blotting. Transforming growth factor‐β mRNA signal was detectable but was not affected by shear. In contrast, human lung fibroblasts (WI‐38) responded to fluid‐induced shear with increased signal for transforming growth factor‐β but not interleukin‐6, mRNA. Both cell types did respond to interleukin‐1α with increased interleukin‐6 mRNA signal. These data demonstrate that distortional forces, such as fluid‐induced shear stress, alter interleukin‐6 levels in normal chondrocytes in vitro and suggest that increased interleukin‐6 expression in osteoarthritic cartilage may result, in part, from alterations in the mechanical loading of the tissue.
Repopulation of laser‐perforated chondroepiphyseal matrix with xenogeneic chondrocytes: An experimental model
Authors: Caruso Enzo M. , Lewandrowski Kai‐Uwe , Ohlendorf Christian , Tomford William W. , Zaleske David J.
Published: February 2005

Growth of chondrocytes into a xenogeneic chondroepiphyseal matrix was investigated in an in vitro experimental model by combining viable calf chondrocytes with chick epiphyseal matrix devoid of viable chondrocytes. The chondrocytes were harvested from the wrist joints of newborn calves and cultured for 2 days. The epiphyses were harvested from the distal femurs and the proximal tibias of fetal chicks after development was arrested at 17 days by freezing. The epiphyseal specimens were prepared in four ways. These included femoral and tibial epiphyses without holes and femoral and tibial epiphyses with holes made by a laser. These epiphyseal specimens were co‐cultured with calf chondrocytes for various periods. After digestion of the epiphyseal matrix, viable chondrocytes were counted in suspension. Chondrocyte division in the matrix was assessed by [3H]thymidine incorporation. The growth of calf chondrocytes into the xenogeneic chick matrix was evaluated by fluorescence microscopy on fresh thick epiphyseal sections. The percentage of viable chondrocytes in the xenogeneic epiphyseal matrix increased with culture time to a maximum at day 21. The addition of laser‐drilled holes was found to extend a plateau of chondrocyte viability until day 29. A decrease in cell viability was detected at later observation points. This study demonstrates that xenogeneic matrix may serve as a morphogenetic scaffold for chondrocytic growth.
Responses of mechanoreceptor neurons in the cat knee joint capsule before and after anterior cruciate ligament transection
Authors: Khalsa Partap S. , Grigg Peter
Published: February 2005

It is known that afferent neurons play a protective role in knees made unstable by transection of the anterior cruciate ligament. However, it is not known whether cutting the anterior cruciate ligament has an effect on the response of the sensory neurons that innervate the joint. In this study, the responsiveness (activation threshold and position sensitivity) of single, mechanically sensitive afferent neurons from the cat knee was evaluated by a series of extension, internal, and external rotations. The anterior cruciate ligament then was cut and the same procedure was repeated. Transection of the ligament increased joint laxity for all types of rotations. The responsiveness of the neurons was not changed significantly by cutting the ligament (p > 0.05). Therefore, capsule afferents continue to behave normally in joints in which the anterior cruciate ligament has been transected.
Musculoskeletal function assessment instrument: Criterion and construct validity
Authors: Engelberg Ruth , Martin Diane P. , Agel Julie , Obremsky William , Coronado Gloria , Swiontkowski Marc F.
Published: February 2005

The Musculoskeletal Function Assessment (MFA) instrument, a health status instrument with 100 self‐reported health items; was designed for use with the broad range of patients with musculoskeletal disorders of the extremities commonly seen in clinical practice. In this paper, we report on its criterion and construct validity. Criterion validity was tested against physicians' ratings of patient functioning (e.g., upper functioning, lower functioning, daily activities, recreational functioning, emotional adjustment, and overall functioning) and standard clinical measures (e.g., grip strength, walking speed, fine motor skills, knee and elbow strength, and range of motion). Significant correlations (p ⩽ 0.05) between its scores, physicians' ratings, and clinical measures support the MFA's criterion validity. Construct validity was demonstrated against existing measures of health status (e.g., measures of lower and upper mobility, activity level and satisfaction, health status, social support, pain, emotional status, and quality of life), in accordance with clinical hypotheses about the effect of musculokeletal disorders on functioning (e.g., type and number of problems, severity of illness or injury, and comorbidites) and by an analysis of demographic characteristics (e.g., sex, education, income, health insurance, and employment) against the MFA scores. Discriminant construct validity was supported in an analysis of MFA scores by patient disease groups (p ⩽ 0.01).
Subfailure injury of the rabbit anterior cruciate ligament
Authors: Panjabi Manohar M. , Yoldas Erol , Oxland Thomas R. , Crisco Joseph J.
Published: February 2005

Ligamentous injuries range in severity from a simple sprain to a complete rupture. Although sprains occur more frequently than complete failures, only a few studies have investigated the phenomena of these subfailure injuries. The purpose of our study was to document the changes in the load‐deformation curve until the failure point, after the ligament has been subjected to an 80% subfailure stretch. Thirteen paired fresh rabbit bone‐anterior cruciate ligament‐bone preparations were used. One of the pairs (control) was stretched until failure; the other (experimental) was first stretched to 80% of the failure deformation of the control and then stretched to failure. Comparisons were made between the load‐deformation curves of the experimental and control specimens. The nonlinear load‐deformation curves were characterized by eight parameters: failure load (Ffail), failure deformation (Dfail), energy until failure (Efail), deformations measured at 5, 10, 25, and 50% of the failure load (D5, D10, D25, and D50, respectively), and stiffness measured at 50% of the failure force (K50). There were no significant differences in the values for Ffail, Dfail, and Efail between the experimental and control ligaments (p > 0.33). In contrast, the deformation values were all larger for the experimental than the control ligaments (p < 0.01). The deformations D5, D10, D25, and D50 (mean ± SD) for the control were 0.36 ± 0.13, 0.49 ± 0.23, 0.81 ± 0.35, and 1.23 ± 0.41 mm. The corresponding deformations for the experimental ligaments were, respectively, 209, 186, 153, and 130% of the control values. K50 was also greater for the experimental ligament (125.0 ± 41.7 N/mm compared with 108.7 ± 31.4 N/mm, p < 0.03). These findings indicate that even though the strength of the ligament did not change due to a subfailure injury, the shape of the load‐displacement curve, especially at low loads, was significantly altered. Under the dynamic in vivo loading conditions of daily living, this may result in increased joint laxity, additional loads being applied to other joint structures, and, with time, to joint problems.
Stable partial debonding of the cement interfaces indicated by a finite element model of a total hip prosthesis
Authors: Lu Zhen , Ebramzadeh Edward , McKellop Harry , Sarmiento Augusto
Published: February 2005

A simplified three‐dimensional finite element model of the femoral component of a cemented total hip prosthesis was used to investigate whether partial debonding at the stem‐cement or bone‐cement interfaces propagates in a stable or unstable manner, and to assess the resultant variation of the stresses within the cement layer. The likelihood of unstable debonding under tensile failure mode was assessed both by a conventional monotonic strength criterion and by a fracture mechanics approach that took into account debonding due to fatigue loading. The model predicted that partial debonding at the cement interfaces would be stable and would not precipitate complete debonding. Among the various bonding conditions that were investigated, the maximum tensile stress within the cement layer was least with a small amount of debonding rather than with complete bonding. These results were consistent with clinical observations of nonprogressive or slowly progressive separation at cement interfaces in cemented femoral components that were otherwise well functioning and asymptomatic.
Biomechanical effects of stress shielding of the rabbit patellar tendon depend on the degree of stress reduction
Authors: Majima Tokifumi , Yasuda Kazunori , Fujii Takashi , Yamamoto Noritaka , Hayashi Kozaburo , Kaneda Kiyoshi
Published: February 2005

A rabbit model was used to discover whether the effects of stress shielding on the mechanical properties of the patellar tendon depend on the degree of stress reduction. Ninety mature female Japanese White rabbits were divided into three groups: completely stress‐shielded, partially stress‐shielded, and shamoperation and contralateral controls. In the experimental groups, tension applied to the patellar tendon was 0%, approximately 30%, and 100%, of the normal tension, respectively, with a polyester artificial ligament. Tensile tests were carried out on patella‐patellar tendon‐tibia complexes harvested 1, 2, 3, 6, or 12 weeks after surgery. The tensile strength decreased in comparison with the sham‐operation group to 50.2, 13.5, 9.7, and 20.7% in the completely stress‐shielded group and to 75.2, 57.6, 59.6, 57.3, and 72.9% in the partially stress‐shielded group. The tensile strength in the completely stress‐shielded group was significantly less than that in the partially stress‐shielded group at 1, 2, 3, and 6 weeks. The cross‐sectional area of the patellar tendon significantly increased to 132, 206, 237, and 136% in the completely stress‐shielded group and to 136, 170, 175, 155, and 127% in the partially stress‐shielded group, compared with the sham‐operation group. The cross‐sectional area of the completely stress‐shielded tendon was significantly larger than that of the partially stress‐shielded tendon at 1, 2, and 3 weeks. This study demonstrated that effects of stress shielding on the mechanical properties of the patellar tendon were dependent on the degree of stress shielding.
Human breast cancer induces osteoclast activation and increases the number of osteoclasts at sites of tumor osteolysis
Authors: Closhisy Denis R , Palkert Diane , Ramnaraine Margaret L. R. , Pekurovsky Ilya , Oursler Merry Jo
Published: February 2005

The cellular mechanism through which osseous breast cancer metastases induce the focal destruction of bone (tumor osteolysis) is unknown. An athymic mouse model designed for the study of tumor osteolysis was developed and the influence of two human breast cancer tumors on bone was studied. Tumor‐induced osteolysis occurred between 7 and 10 weeks after inoculation of mouse femora with MDA‐MB‐231 or MDA‐MB‐435s breast cancer cells. An increase in osteoclast number and an increase in osteoclast size (area) were detected when tumor‐bearing and sham‐injected limbs were compared. In vitro analysis of the influence of the tumor‐conditioned medium on osteoclast‐mediated bone resorption revealed that this conditioned medium stimulated the resorption by increasing both the number of osteoclasts bound to bone and the number of bone resorption pits formed per osteoclast. In addition, in vitro analysis of the influence of breast cancer tumor cells on osteoclast formation or survival, or both, demonstrated that breast cancer cells induced a dramatic increase in the number of osteoclasts detected in culture. Taken in total, these findings suggest that human breast cancer tumors induce osteolysis by enhancing osteoclast adherence to bone, stimulating osteoclast‐mediated bone resorption, and either prolonging the survival of osteoclasts or increasing osteoclast formation.
In vitro bone biocompatibility of poly(anhydride‐co‐imides) containing pyromellitylimidoalanine
Authors: Attawia Mohamed A. , Uhrich Kathryn E. , Botchwey Edward , Langer Robert , Laurencin Cato T.
Published: February 2005

Poly(anhydride‐co‐imides) are currently under study for applications involving bone. The cytotoxicity of a series of poly(anhydride‐co‐imides) with osteoblast‐like cells (MC3T3‐E1) was evaluated. The imide component of the copolymers was based on pyromellitylimidoalanine and the anhydride component was based on either sebacic acid or 1,6‐bis(carboxyphenoxy)hexane. Cell adhesion and proliferation on the surfaces of the polymer discs were observed by environmental scanning electron microscopy. During the first 24 hours of attachment, the cells showed normal morphology when cultured on copolymers containing 1,6‐bis(carboxyphenoxy)hexane. The cells did not adhere to the polymers containing sebacic acid, probably due to the rapid degradation of the polymer surfaces. Concurrently, the effects of polymer breakdown products on osteoblast‐like cells were evaluated by studying their proliferation (cell numbers), viability (dye exclusion), morphology (light microscopy), and phenotypic expression. The morphology of osteoblast‐like cells cultured in the presence of the polymer breakdown products pyromellitylimidoalanine and pyromellitic acid was found to be similar to that of the same cells grown on tissue culture polystyrene and consisted of a characteristic polygonal shape. With use of a monoclonal antibody to osteocalcin, these cells were shown to demonstrate preserved osteoblast phenotype with growth over a 21‐day period. In addition, the cells reached confluency after 3–4 days, similar to cells grown on tissue culture polystyrene. This in vitro evaluation showed that the poly(anhydride‐co‐imides) evaluated are non‐cytotoxic and may be viable biomaterials for orthopaedic applications.
Biomechanical comparison of calf and human spines
Authors: Wilke Hans‐Joachim , Krischak Stefan , Claes Lutz
Published: February 2005

Given the limited availability of human cadaveric specimens and their potential risk of infection, calf spines have been used as substitutes for human spines in the evaluation of spinal implants. Few bio‐mechanical data comparing calf and human spines are available, however. The purpose of this study was to determine the biomechanical properties of the calf spine and to compare them with properties previously reported for the human spine. We determined the range of motion, neutral zone, and stiffness of thoracic and lumbar calf spines (T6 to L6) under pure moment loading in flexion‐extension, axial rotation, and lateral bending. These properties were shown to be similar to those of the human spine. The results suggest that the calf spine can be used as a substitute for the human spine in some in vitro tests.
Effect of tibial attachment location on the healing of the anterior cruciate ligament freeze model
Authors: Bush‐Joseph C. A. , Cummings J. F. , Buseck M. , Bylski‐Austrow D. I. , Butler D. L. , Noyes F. R. , Grood E. S.
Published: February 2005

We studied the healing response of a devitalized anterior cruciate ligament to a treatment of initial anterior‐posterior joint translation in goats. Devitalization and devascularization were achieved by five successive freeze‐thaw cycles. Anterior‐posterior translation was surgically altered by an osteotomy of the tibial attachment of the devitalized ligament and its reattachment either in the anatomical position or in a position 5 mm posterior. Six weeks after the first surgery, the same procedure was performed on the contralateral limb, except that the ligament was reattached in the alternate position. Six months after the initial surgery, femur‐anterior cruciate ligament‐tibia specimens were tested to determine their structural and mechanical material properties. Anatomic ligament placement resulted in reduced anterior‐posterior translation (p < 0.05) and greater anterior joint stiffness (p < 0.05). Maximum load (p < 0.05) and ligament stiffness (p < 0.01) also were greater for the anatomically placed anterior cruciate ligaments. The maximum load for anatomically placed ligaments averaged 1.625 ± 211 N (SEM). The strength of the posteriorly placed anterior cruciate ligament, 895 ± 164 N. was similar to results of historical anterior cruciate autograft reconstructions. Ligament failure occurred near the tibial insertion in the posteriorly placed ligaments more often than in the anatomically placed ligaments (four of five times compared with one of five times). Ligament failure near the tibial insertion occurred with lower mean maximum load than failure at the midsubstance or by bone avulsion (796 compared with 1.592 N: p < 0.05). These data support the hypothesis that ligament laxity is important to the healing and remodeling of anterior cruciate ligament grafts.
Patellar tendon and anterior cruciate ligament have different mitogenic responses to platelet‐derived growth factor and transforming growth factor β
Authors: Spindler Kurt P. , Imro Amy K. , Mayes Charles E. , Davidson Jeffrey M.
Published: February 2005

The healing responses of the anterior cruciate ligament and the patellar tendon differ markedly. The anterior cruciate ligament fails to heal, whereas the patellar tendon heals slowly. The basis of these differences is unknown. Since cellular proliferation is a critical element of healing, we investigated the response to explants of anterior cruciate ligament and patellar tendon from sheep knees to platelet‐derived growth factor‐AB and transforming growth factor β1 as a function of time and dose. Explants cultured for 48, 72, and 96 hours with transforming growth factor β1 (0‐100 ng/ml) or platelet‐derived growth factor‐AB (0‐200 ng/ml) were radiolabeled for the final 24 hours with [3H]thymidine, and DNA synthesis was quantified as trichloroacetic acid‐precipitable radioactivity normalized to dry tissue weight. Statistical analyses (analysis of variance) showed that transforming growth factor β1 induced a significant proliferative response in the anterior cruciate ligament at 96 hours with equivalent responses at 10.50, and 100 ng/ml, whereas the patellar tendon only responded to one condition, 10 ng/ml at 96 hours. Conversely, the patellar tendon had a significant dose‐dependent response to platelet‐derived growth factor‐AB at 72 and 96 hours, whereas the anterior cruciate ligament showed no proliferative response to platelet‐derived growth factor‐AB. The minimal response of anterior cruciate ligament to platelet‐derived growth factor‐AB could explain, at least in part, the poor repair capacity of this tissue. The response of the anterior cruciate ligament to transforming growth factor β suggests that exogenous transforming growth factor β may promote initial healing. Although growth factors have the potential to modulate soft‐tissue repair, tissue responses in tendons and ligaments may vary at different anatomic sites.
Spatial distribution of CD44 and hyaluronan in the proximal tibia of the growing rat
Authors: Noonan Kenneth J. , Stevens Jeff W. , Tammi Raija , Tammi Markku , Hernandez José A. , Midura Ronald J.
Published: February 2005

CD44 has been described as a cell surface hyaluronan receptor present on a variety of different cells, and it is generally assumed to be prevalent in most connective tissues that contain hyaluronan. A major aim of this study was to test that presumption by localizing CD44 and hyaluronan within several tissues of the proximal tibia of the growing rat. Comparison of these profiles would reveal whether CD44 and hyaluronan co‐localize with high fidelity, as would be expected if CD44 were a major hyaluronan binding protein. Using in situ hybridization and immunohistochemistry, CD44 was identified on osteoclasts, chondroclasts, osteocytes, hematopoietic marrow cells, synovial cells, and connective tissue fibroblasts (ligaments, tendons, and fascia). Although the majority of osteocytes expressed CD44, reduced expression was observed for osteoblasts and osteoprogenitor cells. Additionally, CD44 was not detected on chondrocytes from epiphyseal and metaphyseal growth cartilages or in meniscal fibrocartilage. Using biotinylated G1 domain from aggrecan and link protein, hyaluronan was observed in the maturational and hypertrophic zones of all growth cartilages, the synovium and other fibroblastic connective tissues, regional areas of the periosteum and endosteum (around osteoblasts, osteoprogenitor cells, and osteoclasts), osteocyte lacunae, and surrounding blood vessels. In regions of co‐localization for CD44 and hyaluronan, it seems that CD44 is a likely hyaluronan binding protein in several tissues of the proximal tibia. However, it does not appear to be the predominant hyaluronan binding protein in growing cartilages of the weanling rat.
Effects of combined knee loadings on posterior cruciate ligament force generation
Authors: Markolf Keith L. , Slauterbeck James L. , Armstrong Kevin L. , Shapiro Matthew M. , Finerman Gerald A. M.
Published: February 2005

Resultant forces in the posterior cruciate ligament were measured under paired combinations of posterior tibial force, internal and external tibial torque, and varus and valgus moment. The force generated in the ligament from a straight 100 N posterior tibial force was highly sensitive to the angle of knee flexion. For example, at 90 of flexion the mean resultant force in the posterior cruciate ligament was 112% of the applied posterior tibial force, whereas at 0°, only 16% of the applied posterior force was measured in the ligament. When the tibia was preloaded by 10 Nm of external torque, only 9–13% of the 100 N posterior tibial force was transmitted to the posterior cruciate ligament at flexion angles less than 60° at 90° of flexion, 61% was carried by the ligament. This “off‐loading” of the posterior cruciate ligament also occurred when the tibia was preloaded by 10 Nm or internal torque, but only at knee flexion angles between 20 and 40°. The addition of 10 Nm of valgus moment to a knee loaded by a 100 N posterior tibial force increased the mean force in the posterior cruciate ligament at all flexion angles except hyperextension: this represents a common and potentially dangerous loading combination. The addition of 10 Nm of varus moment to a knee loaded by a 100 N posterior tibial force increased the mean force in the posterior cruciate ligament at all flexion angles except hyperextension; this represents a common and potentially dangerous loading combination. The addition of 10 Nm of varus moment to a knee loaded by a 100 N posterior tibial force decreased the mean force in the ligament between 10 and 70° of flexion. External tibial torque (alone or combined with varus or valgus moment) was not an important loading mechanism in the posterior cruciate ligament. The application of internal torque plus varus moment at 90° of flexion produced the greatest posterior cruciate ligament forces in our study and represented the only potential injury mechanism that did not involve posterior tibial force.
SAS is amplified predominantly in surface osteosarcoma
Authors: Noble‐Topham S. E. , Kandel R. A. , Burrow S. R. , Bell R. S. , Eppert K. , Meltzer P. S. , Andrulis I. L.
Published: February 2005

The development of several types of human tumors is related to amplification of genes that are involved in cell growth. The protein products of these genes give the cells a selective growth advantage. The q13–15 region of chromosome 12 is frequently altered in human sarcomas, and the SAS gene has been identified in an amplification unit mapping to this region. Gene amplification of SAS was analyzed to determine the frequency of genetic alteration of this gene in osteosarcoma. Using Southern blot analysis as well as quantitative polymerase chain reaction. SAS was found to be amplified in 10 (36% ) of 28 osteosarcomas. Gene amplification was evaluated in subtypes of osteosarcoma. All seven surface osteosarcomas displayed amplified SAS. In contrast, SAS was amplified in only two (13% ) of 15 intramedullary osteosarcomas. The finding that all surface osteosarcomas demonstrated SAS gene amplification suggests that this gene may play a role in the pathogenesis of osteosarcoma subtypes and that surface osteosarcoma may be genetically different from high‐grade intramedullary osteosarcoma.