bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal measurement of tibial motion relative to the femur during passive displacements in the cat before and after anterior cruciate ligament transection
Authors: Maitland Murray E. , Leonard Tim , Frank Cyril B. , Shrive Nigel G. , Herzog Walter
Published: February 2005

Passive anterior‐posterior displacement and medial‐lateral rotation of the tibia on the femur in the feline knee were assessed before transection of the anterior cruciate ligament, immediately after transection, and 2 and 4 months after transection. Four anaesthetized experimental and three sham‐operated control animals were positioned in a stereotaxic frame. Motions of the tibia relative to the femur were measured with use of 60‐Hz video motion analysis, while a strain‐gauged system allowed measurement of forces and moments applied to the tibia. Displacement at 15 N of anterior force and 30° of knee flexion increased by an average of 6 mm following transection, and stiffness decreased by an average of 6 N/mm. At 2 and 4 months following transection, there were statistically significant reductions in this abnormal displacement. Stiffness during anterior displacement of the tibia at 30° increased significantly from immediately after transection to 4 months. At 90°, mean anterior displacement decreased from 5.1 mm immediately after transection to 2.9 mm at 4 months. Media rotation at 30° of knee flexion was significantly decreased from a mean of 16.5° after transection to a mean of 10.7° at 4 months. Changes in medial rotation at 90°, lateral rotation at 90°, and lateral rotation at 30° were not statistically significant. These results indicate a significant change in secondary constraints to tibial motion in response to knee instability.
Nonlinear dependence of loading intensity and cycle number in the maintenance of bone mass and morphology
Authors: Qin Yi‐Xian , Rubin Clinton T. , McLeod Kenneth J.
Published: February 2005

The daily stress stimulus theory of bone adaptation was formulated to describe the loading conditions necessary to maintain bone mass. This theory identifies stress/strain magnitude and loading cycle number as sufficient to define an appropriate maintenance loading signal. Here, we extend the range over which loading cycle number has been evaluated to determine whether the daily stress stimulus theory can be applied to conditions of very high numbers of loading cycles at very low strain magnitudes. The ability of a relatively high‐frequency (30‐Hz) and moderate‐duration (60‐minute) loading regimen to maintain bone mass in a turkey ulna model of disuse osteopenia was evaluated by correlating the applied strain distributions to site‐specific remodeling activity. Changes in morphology were investigated following 8 weeks of disuse compared with disuse plus daily exposure to 108,000 applied loading cycles sufficient to induce peak strains of approximately 100 microstrain. A strong correlation was observed between the preservation of bone mass and longitudinal normal strain (R = 0.91) (p < 0.01). The results confirm the strong antiresorptive influence of mechanical loading and identify a threshold near 70 microstrain for a daily loading cycle regimen of approximately 100,000 strain cycles. These results are not consistent with the daily stress stimulus theory and suggest that the frequency or strain rate associated with the loading stimulus must also play a critical role in the mechanism by which bone responds to mechanical strain.
Cultured human ankle and knee cartilage differ in susceptibility to damage mediated by fibronectin fragments
Authors: Kang Yong , Koepp Holger , Cole Ada A. , Kuettner Klaus E. , Homandberg Gene A.
Published: February 2005

According to numerous cadaveric, radiographic, and clinical studies, ankle and knee joints differ in susceptibility to osteoarthritis. To test for biochemical differences in susceptibility to damage, a chondrocytic chondrolysis system has been utilized. In this system, fibronectin fragments are added to cultured cartilage explants, resulting in enhanced release of catabolic cytokines. induction of matrix metalloproteinases, temporary suppression of proteoglycan synthesis, and consequently, severe loss of cartilage proteoglycan. We found that the addition of an amino‐terminal thrombin‐generated 29‐kDa fibronectin fragment to cultured knee cartilage from 14 donors (average age: 53 years) usually caused a 30–50% decrease in proteoglycan content by day 7. However, of the ankle cartilage specimens examined from 21 donors (average age: 50 years), only three showed damage by, day 7. one by day 14, and six by day 21. and 11 were not damaged until day 28. For eight of the donors (average age: 44 years), both knee and ankle cartilages were obtained; this allowed comparison between tissues from the same donor. The analysis showed that the ankle cartilage was much more refractory to damage than was the knee cartilage from the same donor. These data clearly show differences between ankle and knee cartilage in susceptibility to the fibronectin fragments and suggest the feasibility of use of these fragments for discerning differences in homeostasis of the ankle and knee cartilage.
Distal radius fractures: Mechanisms of injury and strength prediction by bone mineral assessment
Authors: Augat Peter , Iida Hiroyuki , Jiang Yebin , Diao Edward , Genant Harry K.
Published: February 2005

The strength of the radius depends on the mechanical properties of cancellous and cortical bone. By assessing both compartments quantitatively with bone densitometry. we tried to identify the specificity of each in predicting the load at which the distal raius will fracture. Twenty human cadaver forearms were scanned for bone mineral and geometric properties with quantitative computed tomography and dual x‐ray absorptiometry. In both a neutral loading situation and one in which the wrist was extended 45°, the load distribution was determined with pressure‐sensitive films, and a fracture simulating a fall on the hand was produced with a material testing machine. Fractures that occur with the wrist in extension were produced by a central impact of the scaphoid onto the radiocarpal joint, and those that occur under neutral loading conditions were produced by a more commonly distributed loading pattern. The load at fracture was most specifically predicted (r2 = 0.74) by bone mineral and geometric measures of the cortex at the shaft of the radius. Bone mineral density measures of trabecular (r2 = 0.64) and total (r2 = 0.66) bone were less successful in predicting the fracture load. After adjustment for bone size, the geometric and density measures revealed similar specificity. Cortical bone, therefore, contributes significantly to the strength of the distal radius and may play an important role in the prediction of osteoporotic wrist fractures.
In situ forces in the posterolateral structures of the knee under posterior tibial loading in the intact and posterior cruciate ligament‐deficient knee
Authors: Höher Jürgen , Harner Christopher D. , Vogrin Tracy M. , Baek Goo Hyun , Carlin Gregory J. , Woo Savio L‐Y.
Published: February 2005

The posterolateral structures of the knee consist of a complex anatomical architecture that includes several components with both static and dynamic functions. Injuries of the posterolateral structures occur frequently in conjunction with ruptures of the posterior cruciate ligament. To investigate the role of the posterolateral structures in maintaining posterior knee stability, we measured the in situ forces in the posterolateral structures and the distribution of force within the structures major components, i.e., the popliteus complex and the lateral collateral ligament, in response to a posterior tibial load. Eight cadaveric knees were tested. With use of a robotic/universal force‐moment sensor testing system, a posterior tibial load of 110 N was applied to the knee, and the resulting five‐degree‐of‐freedom kinematics were measured at flexion angles of 0, 30, 60, 75, and 90°. The knees were tested first in the intact state and then after the posterior cruciate ligament had been resected. These tests were also performed with an additional load of 44 N applied at the aponeurosis to simulate contraction of the popliteus muscle. In the intact knee, the in situ forces in the posterolateral structures were found to decrease with increasing knee flexion. After the posterior cruciate ligament was sectioned, these forces increased significantly at all angles of flexion. With no load applied to the popliteus muscle, the in situ forces in the popliteus complex were similar to those in the lateral collateral ligament. However, with a load of 44 N applied to the popliteus muscle, in situ forces in the popliteus complex were three to five, times higher than those in the lateral collateral ligament. These results reveal that in response to posterior tibial loads, the posterolateral structures play an important role at full extension in intact knees and at all angles of flexion in posterior cruciate ligament‐deficient knees. The popliteus muscle appears to be a major stabilizer under this loading condition; thus, the inability to restore its function may be a cause of unsatisfactory results in reconstructive procedures of the posterolateral structures of the knee.
Immobilization increases the vulnerability of rabbit medial collateral ligament autografts to creep
Authors: Boorman Richard S. , Shrive Nigel G. , Frank Cyril B.
Published: February 2005

Rehabilitation after soft‐tissue autograft reconstructions is controversial because there is indirect evidence that some grafts fail by creeping over time. The vulnerability of soft‐tissue grafts to creep over healing time and the effects of the load environment during healing on this vulnerability have never been studied specifically. We hypothesized that immobilization would decrease the magnitude of the vulnerability of ligament grafts to creep. Thirty‐nine skeletally mature New Zealand White rabbits underwent a standardized medial collateral ligament autograft procedure to the right hindlimb, and 19 of the rabbits also had the limb rigidly pinned into flexion. Subgroups were killed at 3 or 8 weeks, and all isolated tibia/medial collateral ligament/femur complexes were tested for creep at 4.1 MPa under a standardized protocol. Eight normal medial collateral ligament controls were tested similarly. Results showed that all grafts were quantitatively more susceptible to cyclic and static creep than were normal medial collateral ligament controls (p < 0.05). By 3 weeks of healing, immobilization significantly increased the magnitude of the vulnerability of the grafts to cyclic, static, and total creep (all: p < 0.05). Furthermore, the grafts had more unrecovered creep strain than did the controls following a 20‐minute recovery period. Contrary to our hypothesis, immobilization resulted in increased vulnerability of these ligament autografts to creep even with this relatively nonprovocative test of short duration and low stress. We postulate that following immobilization, this increase in the magnitude of susceptibility of the grafts to creep will result in functionally significant elongation of the graft if it is exposed to higher loads and over longer periods of time in vivo.
In vitro strength comparison of hydroxyapatite cement and polymethylmethacrylate in subchondral defects in caprine femora
Authors: Crawford Kevin , Berrey B. Hudson , Pierce William A. , Welch Robert D.
Published: February 2005

Hydroxyapatite cement was investigated in situ for the reconstruction of juxta‐articular defects. Polymethylmethacrylate is currently the most commonly used material for the reconstruction of bone defects following the exteriorization and curettage of aggressive benign tumors. In vitro, we compared the effects of hydroxyapatite cement and polymethylmethacrylate in restoring the stiffness of the subchondral plate in a caprine femoral defect model, fen matched pairs of caprine femora underwent nondestructive compression testing normal to the load‐bearing surface. A standardized subchondral defect 12 mm in diameter was created in the medial femoral condyle. Compression testing was repeated to determine the reduction in stiffness caused by the defect. Each femur from each pair was randomly assigned to one of two groups (n = 9), and the defects were augmented with either polymethylmethacrylate or hydroxyapatite cement. After 12 hours, compression tcsting/vas repeated to determine the subchondral stiffness after augmentation. Compared with intact femora, the defect specimens that were later treated with either polymethylmethacrylate or hydroxy‐npatite cement exhibited stiffness values of 70 (386 ± 107 N/mm) and 59% (343 ± 94 N/mm) respectively, which represented a significant reduction in stiffness (p = 0.05). Augmentation with polymethylmethacrylate or hydroxyapatite cement restored stiffness by 81 (450 111 N/mm) and 71% (413 ± 115 N/mm), respectively, of tile values of intact specimens. Hydroxyapatite cement restored stiffness significantly (p = 0.05) over the stiffness of the nonaugmented defect compared with the stiffness after augmentation with polymethylmethacrylate (p = 0.12). Neither polymethylmethacrylate nor hydroxyapatite cement restored stiffness to that of intact femora (p = 0.05). In the current defect model, hydroxyapatite cement was comparable with poly‐moihylmethacrylate in restoring subchondral stiffness. Unlike polymethylmethacrylate, however, hydroxy‐apalile cement has the following advantages: it is osteoconductive, is replaced by host bone, and avoids the potential for thermal necrosis. Hydroxyapatite cement may therefore provide a viable alternative to poly‐methylmethacrylate lor augmentation of juxta‐articular and other bone defects.
Effects of fibronectin on articular cartilage chondrocyte proteoglycan synthesis and response to insulin‐like growth factor‐I
Authors: Martin James A, , Buckwalter Joseph A.
Published: February 2005

Fibronectin, a ubiquitous glycoprotein of the extracellular matrix, serves as a substrate for cell attachment. Binding to fibronectin through cell‐surface receptors promotes a flattened cell shape, stimulates the phosphorylation of intracellular protein, and changes the pattern of gene expression. Although fibronectin is abundant in normal articular cartilage, its effects on chondrocytes are not well understood. Proteolytic fragments of fibronectin stimulate the catabolism of matrix in articular cartilage and may promote the degeneration of cartilage in osteoarthritis; however, intact fibronectin may regulate other aspects of matrix metabolism, including matrix synthesis. To determine whether intact fibronectin affects the synthetic activity of chondrocytes, as well as to determine the responses of chondrocytes to the anabolic growth factor.insulin‐like growth factor‐I, we compared the incorporation of [35S] by articular chondrocytes of the rat culture.din the presence and absence of commercially prepared cellular fibronectin and 0, 10, or 100 ng/ml recomBinanf human insulin‐like growth factor‐I. Monolayer and alginate suspension cultures were compared to determine whether responses differed under conditions in which fibronectin promoted a flattened cell shape (monolayer culture) and under those in which cells maintained a spherical shape (alginate culture). In alginate cultures, fibronectin alone stimulated the incorporation of [35S]. Fibronectin with 10 ng/ml insulin‐like growth factor‐I had additive effects in alginate culture, producing the maximum incorporation of [35S]. In monolayer cultures, fibronectin did not stimulate incorporation and blocked stimulation by 100 ng/ml insulin‐like growth factor‐I. The cells from the monolayer culture were much less active synthetically (at all doses of the growth factor) than those culture in alginate. Thus, fibronectin enhanced proteoglycan synthesis and the response to insulin‐like growth factor‐I in alginate but inhibited the response to the growth factor in monolayers. These observations suggest intact fibronectin may contribute to the maintenance or repair of the matrix of articular cartilage by stimulating proteoglycan synthesis.
Noninvasive technique for measuring in vivo three‐dimensional carpal bone kinematics
Authors: Crisco Joseph J. , McGovern Robert D. , Wolfe Scott W.
Published: February 2005

Our present knowledge of the three‐dimensional kinematic behavior of skeletal joints has been largely acquired with cadaveric models and use of invasive monitoring. In the wrist, the small size and complex motion of the carpal bones present a difficult challenge for implanted internal or external marker systems. This paper describes a technique for quantifying the three‐dimensional kinematics of the wrist and carpal bones in vivo using noninvasive computed tomographic imaging. An error analysis employing a cadaveric specimen suggests that noninvasive carpal kinematics can be measured with an accuracy within 2° of rotation and 1 mm of translation along a helical axis of motion. The in vivo application of this technique is illustrated with a single normal individual. Potential applications include the quantification of normal wrist motion, analysis of pathomechanics, and evaluation of surgical intervention. The technique is also applicable to other joints and imaging modalities.
Musculoskeletal function assessment: Reference values for patient and non‐patient samples
Authors: Engelberg Ruth , Martin Diane P. , Agel Julie , Swiontkowski Marc F. , Wright James
Published: February 2005

Although researchers and clinicians are encouraged to use health‐status questionnaires to evaluate, monitor, and modify care, their use is hindered by the lack of reference values. Without reference values, it is difficult to interpret or evaluate questionnaire scores. In this paper, we present reference values for the Musculoskeletal Function Assessment, a 101‐item health‐status questionnaire designed and validated for patients with a broad range of musculoskeletal disorders. We describe reference values for two samples: non‐patients (n = 123) and patients with isolated extremity injuries (n = 274). For the non‐patient sample, descriptive statistics are presented by age and gender, measured at one point in time. For the patient sample, descriptive statistics are provided for seven Orthopaedic Trauma Association/AO diagnostic groups, measured at two points in time. Reference values for changes in the Musculoskeletal Function Assessment total score are described for patients 3 and 9 months and 6 and 12 months after injury. The total scores by post‐injury interval, across the diagnostic groups, are significantly better at follow‐up than at baseline (p = 0.00). Reference values for changes in total scores are also described in terms of these diagnostic groups across post‐injury intervals. Musculoskeletal Function Assessment total scores for Orthopaedic Trauma Association/AO diagnostic groups are significantly better at follow‐up than at baseline (p < 0.03). Changes in the total score are also tested for responsiveness with use of standardized response means. Large effects are demonstrated for patients completing the Musculoskeletal Function Assessment at 3 and 9 months (1.03), and small effects are demonstrated for those completing it at 6 and 12 months (0.49). Moderate and large effects are demonstrated for Orthopaedic Trauma Association/AO diagnostic groups across post‐injury intervals.
In situ expression of collagen and proteoglycan genes during development of fibrocartilage in bovine deep flexor tendon
Authors: Perez‐Castro Ana V. , Vogel Kathryn G.
Published: February 2005

A region of fibrocartilage develops in bovine deep flexor tendon where the tissue wraps around bone and is subjected to compressive and shear forces in addition to tension. There is no fibrocartilage at this location in fetal tendon or in adjacent adult tendon that is subjected to tensional load only. We investigated the development of fibrocartilage in tendon using in situ hybridization to localize cells that express collagen and proteoglycan genes typical of either tendon or cartilage. The signal for type I collagen and decorin was high in cells throughout fetal and newborn tendon, as is expected in a growing tissue composed predominantly of type I collagen. No signal for aggrecan was seen in either fetal or newborn tendon. No hybridization with any of the probes for collagen or proteoglycan was detected in cells in the tensional region of adult tendon, indicating that the cells in this tissue are normally quiescent. However, the cells in the fibrocartilage of adult tendon displayed a high level of expression for types I and II collagen, decorin, biglycan, and aggrecan. This suggests that the fibrocartilage in adult tendon is a dynamic tissue. Expression of type IIA collagen is considered a marker of prechondrocytes. Type IIA collagen gene expression was present throughout both the tensional and compressed regions of fetal and newborn tendon but was absent in cartilaga and adult tendon. This suggests that cells located throught fetal tendon may have the capacity to develop as chondrocytes. Fibrocartilage signal was detected for type I collagen in 75% of the cells and for type II collagen in 50% of the cells at one location in adult tendon, suggesting that some cells in this tissue could have expressed mRNA for both type I and type II collagen.
Development of an extremely wear‐resistant ultra high molecular weight polythylene for total hip replacements
Authors: McKellop Harry , Shen Fu‐wen , Lu Bin , Campbell Patricia , Salovey Ronald
Published: February 2005

Osteolysis induced by ultra high molecular weight polyethylene wear debris is one of the primary factors limiting the lifespan of total hip replacements. Crosslinking polyethylene is known to improve its wear resistance in certain industrial applications, and crosslinked polyethylene acetabular cups have shown improved wear resistance in two clinical studies. In the present study, crosslinked polyethylene cups were produced by two methods. Chemically crosslinked cups were produced by mixing a peroxide with ultra high molecular weight polyethylene powder and then molding the cups directly to shape. Radiation‐crosslinked cups were produced by exposing conventional extruded ultra high molecular weight polyethylene bar stock to gamma radiation at various doses from 3.3 to 100 Mrad (1 Mrad = 10 kGy), remelting the bars to extinguish residual free radicals (i.e., to minimize long‐term oxidation), and then machining the cups by conventional techniques. In hip‐joint simulator tests lasting as long as 5 million cycles, both types of crosslinked cups exhibited dramatically improved resistance to wear. Artificial aging of the cups by heating for 30 days in air at 80°C induced oxidation of the chemically crosslinked cups. However, a chemically crosslinked cup that was aged 2.7 years at room temperature had very little oxidation. Thus, whether substantial oxidation of chemically crosslinked polyethylene would occur at body temperature remains unclear. The radiationcrosslinked remelted cups exhibited excellent resistance to oxidation. Because crosslinking can reduce the ultimate tensile strength, fatigue strength, and elongation to failure of ultra high molecular weight polyethylene, the optimal crosslinking dose provides a balance between these physical properties and the wear resistance of the implant and might substantially reduce the incidence of wear‐induced osteolysis with total hip replacements.
Three‐dimensional knee kinematics and stability in patients with a posterior cruciate ligament tear
Authors: Jonsson Håkan , Kärrholm Johan
Published: February 2005

The three‐dimensional kinematics of the knee were studied from 5 months to 15 years after unilateral posterior cruciate ligament tears occurred in eight patients. All but two patients had signs of additional ligament injuries. Repeated radiostereometric examinations were conducted when the patients ascended a platform (step‐up test) and during an instrumented anterior‐posterior drawer test with the knee at 30° of flexion. No changes in knee kinematics were observed during the step‐up test, whereas increased anteriorposterior laxity (3.8–11.3 mm) was recorded for all patients. Four of the patients had an increased side‐to‐side difference (more than 2 mm) in anterior as well as posterior laxity. A rupture of the posterior cruciate ligament can be diagnosed at 30° of knee flexion, but an increase in anterior laxity can erroneously be interpreted as an injury of the anterior cruciate ligament. The unaffected kinematics of the knee suggest that factors such as joint load and congruity and muscle activity can compensate for the absent posterior cruciate ligament during static examinations.
Expression of α‐smooth muscle actin in canine intervertebal disc cells in situ and in collagen‐glycosaminoglycan matrices in vitro
Authors: Schneider T. O. , Mueller S. M. , Shortkroff S. , Spector M.
Published: February 2005

The objective of this study was to investigate the presence of a contractile actin isoform, α‐smooth muscle actin, in annulus fibrosus cells in situ and in two and three‐dimensional cultures. Annulus fibrosus cells were isolated from healthy adult dogs, serial passaged, and then injected into porous collagen‐glycosaminoglycan copolymers consisting of either type‐I or type‐II collagen. α‐Smooth muscle actin was detected in the cells in tissue samples and in culture by immunohistochemistry. The number of cells and glycosaminoglycan content of the matrices were determined after 1, 7, and 14 days, and the diameters of the specimens were measured every 2 days. Although few annulus fibrosus cells in vivo displayed the presence of the α‐smooth muscle actin isoform, most cells in two‐dimensional culture demonstrated this phenotype. The contractile behavior of these cells was shown by the cell‐mediated contraction of type‐I collagen‐ glycosaminoglycan scaffolds after 8 days in culture. Glycosaminoglycan production was not significantly different in the seeded type‐I matrices than in the unseeded matrices, whereas the seeded type‐II matrices had a significant increase in glycosaminoglycan production between days 1 and 14 compared with the unseeded controls. This is the first report of both the expression of the contractile α‐smooth muscle actin isoform in intervertebral disc cells and the ability of the cells to contract a collagen matrix. This finding could aid in better understanding the nature of cells in the annulus.
Cartilage induction by controlled mechanical stimulation in vivo
Authors: Tägil Magnus , Aspenberg Per
Published: February 2005

To study mechanical control of tissue differentiation, we designed a new version of the previously described bone conduction chamber. The bone conduction chamber consists of a cylindrical titanium chamber for implantation in the rat tibia. It has tissue ingrowth openings at one end, located subcortically, and the other end protrudes into the subcutis. The newly developed load chamber has a mobile piston so that an external compressive load can be transferred to the tissue within the chamber. Sprague‐Dawley rats had a regular bone conduction chamber implanted in one tibia and a load chamber implanted in the other. Mesenchymal tissue was allowed to grow into the chamber for 3 weeks before the mechanical loading was started. Thereafter, twice a day, 20 cycles of compressive load were applied with a frequency of 0.17 Hz to the load chamber. This was estimated to produce a compressive hydrostatic stress of 2 MPa. The chambers, harvested after 7 weeks of loading, all contained newly formed bone. The bone ingrowth distance into the chamber was decreased in the loaded specimens compared with the contralateral unloaded controls (p = 0.01). Instead, cartilage was found in the loaded chambers next to the piston. Beneath the cartilage was a dense bone plate under which a marrow cavity had formed. No cartilage was found in the unloaded controls, but the architecture of the bone and marrow cavity was similar to that of the loaded specimens. We conclude that this model allows load to be transmitted onto the ingrowing tissue and that the load parameters used cause this tissue to differentiate into cartilage close to the piston.
Hyaluronic acid‐based polymers as cell carriers for tissue‐engineered repair of bone and cartilage
Authors: Solchaga Luis A. , Dennis James E. , Goldberg Victor M. , Caplan Arnold I.
Published: February 2005

Culture‐expanded bone marrow‐derived mesenchymal progenitor cells differentiate into chondrocytes or osteoblasts when implanted subcutaneously in vivo in combination with an appropriate delivery vehicle. This in vivo implantation technique is used to test new materials as putative delivery vehicles in skeletal tissue‐engineering models. HYAFF 11 and ACP sponges, two biomaterials based on hyaluronic acid modified by esterification of the carboxyl groups of the glucuronic acid, were tested as osteogenic or chondrogenic delivery vehicles for rabbit mesenchymal progenitor cells and compared with a well characterized porous calcium phosphate ceramic delivery vehicle. The implant materials were examined by scanning electron microscopy for differences in pore structure or cellular interactions, were quantified for their ability to bind and retain mesenchymal progenitor cells, and were examined histologically for their ability to support osteogenesis and chondrogenesis after subcutaneous implantation into nude mice. The ACP sponge bound the same number of cells as fibronectin‐coated ceramic, whereas the HYAFF 11 sponge bound 90% more. When coated with fibronectin, ACP and HYAFF 11 bound, respectively, 100 and 130% more cells than the coated ceramics. HYAFF 11 sponge composites retained their integrity after the 3 or 6‐week incubation period in the animals and were processed for histomorphometric analysis. As a result of rapid degradation or resorption in vivo, ACP sponges could not be recovered after implantation and could not be analyzed. HYAFF 11 sponges presented more area available for cell attachment and more available volume for newly formed tissue. Following loading with mesenchymal progenitor cells and implantation, the pore of the sponges contained more bone and cartilage than the pores of ceramic cubes at either time point. Thus, relative to ceramic, HYAFF 11 sponges allow incorporation of twice as many cells and produce a 30% increase in the relative amount of bone and cartilage per unit area. Hence, the hyaluronic acid‐based delivery vehicles are superior to porous calcium phosphate ceramic with respect to the number of cells loaded per unit volume of implant, and HYAFF 11 sponges are superior to the ceramics with regard to the amount of bone and cartilage formed. Additionally, hyaluronic acid‐based vehicles have the advantage of degradation/resorption characteristics that allow complete replacement of the implant with newly formed tissue.
Shear strength of the physis varies with anatomic location and is a function of modulus, inclination, and thickness
Authors: Williams John L. , Vani John N. , Eick J. David , Petersen Erik C. , Schmidt Thomas L.
Published: February 2005

Slipped capital femoral epiphysis involves the gradual displacement of the femoral head relative to the neck. Many theories have arisen to explain this slip. Frequently cited etiological factors include increases in physeal thickness and inclination. Slipped epiphysis has been postulated to result from shear overload that causes separation through the hypertrophic cellular zone. We sought to answer the following questions: (a) Do significant regional differences in strength and stiffness exist within a given physis? (b) Are regional differences in resistance to shear related to thickness and inclination of the physis? (c) Does physeal compression cause mammillary interdigitation to begin sooner and increase the resistance to shear before, during, and after failure? (d) Does shear failure occur at displacements detectable by radiography? and (e) Does cleavage occur throughout the entire columnar zone, and do the chondrocyte columns remain intact on both sides of the cleavage plane? We prepared beam‐shaped microstructural samples from different sites of the bovine proximal tibial physis. We determined thickness, inclination, ultimate stress and strain, modulus, and strain energy density at ultimate stress as a function of location. Using scanning electron microscopy, we also examined the entire failed surface of several samples. Forty‐eight samples were tested by displacing the epiphysis end anteriorly, without axial (across the thickness) constraint; 41 were sheared while an average axial compressive stress of 0.3 MPa was applied to the physis. The posterior region had the greatest strength and stiffness, lowest physeal thickness, and steepest inclination. Compressing the plate did not increase the shear strength or tangent modulus. Ultimate strength varied inversely with thickness and increased when shearing up steeper inclinations; however, it was more strongly associated with the modulus, implying that additional factors control both strength and modulus. Scanning electron microscopy revealed that the plane of fracture differed widely between and within samples, involving all zones of the growth plate. On either side of the fracture, individual chondrocyte columns remained intact, although separated from neighboring columns.
Comparative study of normal and osteoarthritic canine synovial fluid using 500 MHz 1H magnetic resonance spectroscopy
Authors: Damyanovich A. Z. , Staples J. R. , Chan A. D. M. , Marshall K. W.
Published: February 2005

High resolution 1H nuclear magnetic resonance spectroscopy has been used to investigate and compare the metabolic profiles of normal and osteoarthritic synovial fluids in a canine model of osteoarthritis. The spectra of osteoarthritic synovial fluid showed (a) increased concentiations of lactate, pyruvate, lipoproteinassociated fatty acids, and glycerol as well as the ketones hydroxybutyrate and hydroxyisobutyrate, (b) reduced levels of glucose, and (c) elevated levels of N‐acetylglycoproteins, acetate, and acetamide compared with healthy normal canine synovial fluid. An increase was also observed in the concentrations of the amino acids alanine and isoleucine. These results suggest that (a) the intaarticular environment in canine osteoarthritis is more hypoxic and acidotic than in a normal joint, (b) lipolysis may play an increasingly important role as a source of energy in osteoarthritis, and (c) the N‐acetylglycoprotein polymer component of synovial fluid (mostly hyaluronan) seems to be increasingly fragmented and degraded into acetate by way of an acetamide intermediate with progressive osteoarthritis. The observed changes in the biochemical profile of canine osteoarthritic synovial fluid may be useful in understanding alterations in joint metabolism consequent to arthritic diseases and helpful in identifying potential markers of osteoarthritis.
Accelerating bone formation and earlier healing after using demineralized bone matrix for limb lengthening in rabbits
Authors: Hagino Tetsuo , Hamada Yoshiki
Published: February 2005

We studied the effects of grafting with demineralized bone matrix during lengthening of the tibia in young Japanese White rabbits. The demineralized bone matrix was made from frozen cortical bone harvested from other rabbits. A 5‐mm gap was created in the tibial diaphysis by a subperiosteal osteotomy; a maximum of 20 mm (2–3 mm/day) of tibial lengthening was reached in a week with use of an external fixator. The control group of 20 rabbits did not receive an implant; the group of 21 experimental rabbits received an implant of demineralized bone matrix in the surgical gap. The control group failed to demonstrate radiographic callus 5 weeks after surgery, and nonunion was persistent after 1 year. In the group with demineralized bone matrix, new radiodensity was demonstrated within the lengthening gap at 3 weeks, with a gradual increase in bone density to 85% that of the intact tibia after 12 weeks. Bone union was seen within 1 year for all experimental animals for whom the external fixator was removed 8 weeks after the procedure. These bones showed normal bone structure histologically. The lengthening was carried out at a rapid distraction rate of 2–3 mm/day; therefore, this method allows for satisfactory bone formation at a faster rate than normal.
Osteochondral progenitor cells in acute and chronic canine nonunions
Authors: Boyan B. D. , Caplan A. I. , Heckman J. D. , Lennon D. P. , Ehler W. , Schwartz Z.
Published: February 2005

This study examined the ability of cells isolated from early healing segmental defects and from tissue from chronic nonunions to support bone and cartilage formation in vivo and their response to transforming growth factor‐betal in vitro. Ostectomies (3 mm) were created in the radial diaphysis of four dogs. The dogs were splinted 3–5 days postoperatively and then allowed to bear full weight. At 7 days, tissue in the defect was removed and any periosteum was discarded; cells in the defect tissue were released by enzymatic digestion. The dogs were splinted again and allowed to bear full weight for 12 weeks. Radiographs confirmed a persistent nonunion in each dog. Defect tissue was again removed, any periosteum was discarded, and cells were isolated. Cells were also obtained from the defect tissue by nonenzymatic means with use of explant cultures. One‐half of the tissue and one‐half of any preconfluent, first‐passage cultures were shipped to Cleveland by overnight carrier. At second passage, cells were loaded into ceramic cubes and implanted into immunocompromised mice for 3 or 6 weeks. Harvested cubes were examined histologically for cartilage and bone with use of a semiquantitative scoring system. Confluent fourth‐passage cultures of 7 and 84‐day defect tissue cells were cultured with 0.03–0.88 ng/ml transforming growth factor‐betal for 24 hours, and [3H]thymidine incorporation and alkaline phosphatase specific activity were determined. Donor‐dependent differences were noted in the rate at which defect cells achieved confluence; in general, cells from 7‐day tissue divided most rapidly. Seven‐day defect cells formed less bone and at a slower rate than was seen in the ceramic cubes containing samples from day 84. Cells derived enzymatically behaved similarly to those from explant cultures. Ceramic cubes contained fibrous connective tissue, cartilage, bone, and fat, indicating that multipotent cells were present. Stimulation of [3H]thymidine incorporation in response to transforming growth factor‐betal was donor dependent and variable; only two of six separate isolates of cells exposed to it had measurable alkaline phosphatase activity (which was relatively low), and none of the cultures exhibited an increase in response to transforming growth factor‐betal for 24 hours. This indicates that mesenchymal progenitor cells are present in the healing defect tissue at 7 and 84 days and that the relative proportion of osteochondroprogenitor cells is greater at the later time. The response to transforming growth factor‐beta1 is typical of multipotent mesenchymal cells but not of committed chondrocytes or osteoblasts, indicating that these committed and differentiated cells are not present in early stages of healing and suggesting that their differentiation is inhibited in chronic nonunion.
Length changes of the hamstrings and adductors resulting from derotational osteotomies of the femur
Authors: Schmidt Deanna J. , Arnold Allison S. , Carroll Norris C. , Delp Scott L.
Published: February 2005

Derotational osteotomies of the femur are frequently performed to treat persons with cerebral palsy who walk with excessive internal rotation of the hip. However, whether these procedures stretch or slacken the surrounding muscles appreciably is unknown. Determination of how muscle lengths are altered by derotational osteotomies is difficult because the length changes depend not only on the osteotomy site and the degree of derotation, but also on the anteversion angle of the femur and the rotational position of the hip. We have developed a three‐dimensional computer simulation of derotational osteotomies, tested by anatomical experiments, to examine how femoral anteversion, hip internal rotation, and derotation affect the lengths of the semitendinosus, semimembranosus, biceps femoris long head, adductor longus, adductor brevis, and gracilis muscles. Simulation of derotational osteotomies at the intertrochanteric, subtrochanteric, or supracondylar levels decreased the origin‐to‐insertion lengths of the hamstrings and gracilis in our model by less than 8 mm (1.8%). Hence, the lengths of the hamstrings and gracilis are not likely to be altered substantially by these procedures. The origin‐to‐insertion lengths of the adductor longus and adductor brevis decreased less than 4 mm (1.9%) with subtrochanteric correction in our model, but the length of adductor brevis increased 8 mm (6.3%) with 60° of intertrochanteric derotation. These muscles are also unlikely to be affected by derotational osteotomies, unless a large degree of intertrochanteric derotation is performed.
Sparing radiation‐induced damage to the physis by radioprotectant drugs: Laboratory analysis in a rat model
Authors: Tamurian R. M. , Damron T. A. , Spadaro J. A.
Published: February 2005

The radioprotectant compound amifostine (S‐2{3‐aminopropylamino}‐ethylphosphorothioc acid), administered prior to radiotherapy, has been demonstrated to provide differential protection of normal cells from the damaging effects of ionizing radiation. The aim of this pilot was to determine if amifostine could preserve the integrity of, or minimize the damage to, the physis during exposure to radiation in an animal model. Thirty weanling Sprague‐Dawley rats were randomized into five groups of six animals each. Groups 1 and 2 received a single exposure to radiation consisting of 12.5 and 17.5 Gy, respectively. Groups 3 and 4 received similar exposures of 12.5 and 17.5 Gy, respectively, but with prior administration of amifostine at 100 mg/kg. Group 5 (control) received neither radiation nor amifostine. At 6 weeks, femoral and tibial lengths were measured in treated and untreated hindlimbs and compared with the baseline lengths to calculate growth. Concordant with previous reports in the literature, the radiation doses of 12.5 and 17.5 Gy reduced net femoral growth in length by a mean of 23% (range = 12–33%, SD = 7.41) and 59% (range = 54–64%, SD = 4.45), respectively, in the irradiated limb. Amifostine reduced anticipated growth loss normally resulting from a single 12.5‐Gy radiation dose by 48.9% in the femur, 13.1% in the tibia, and 27.6% overall in the total limb (p ⩽ 0.05). Similarly, anticipated growth loss from a single 17.5‐Gy radiation dose was reduced by 30.8% in the femur, 20.3% in the tibia, and 25.7% overall in the total limb (p ⩽ 0.05). Amifostine administered prior to clinically relevant radiation exposures significantly reduced the amount of anticipated growth arrest in our animal model.
Motor functional and morphological findings following end‐to‐side neurorrhaphy in the rat model
Authors: Liu Kang , Chen Long‐En , Seaber Anthony V. , Goldner Richard V. , Urbaniak James R.
Published: February 2005

Nerve repair cannot always be achieved by the conventional end‐to‐end technique. This study evaluated the functional recovery of nerves repaired with end‐to‐side neurorrhaphy in a rat model. The right peroneal nerves of 80 female rats were transected and divided into four groups. In group A, the nerve ends were separated and remained unrepaired; in group B, the distal peroneal ends were directly sutured to the epineurium of the tibial nerves in end‐to‐side fashion; in group C, the distal ends were sutured through an epineurial window at the repair site in end‐to‐side fashion; and in group D, the nerve ends were reconnected by the traditional end‐to‐end technique. Evaluation included gait analysis by calculation of a peroneal functional index, measurement of contractile function of the extensor digitorum longus muscle, wet weight of the extensor digitorum longus, and histological examination. The findings of this study suggested the following: (a) end‐to‐side neurorrhaphy allows effective motor functional recovery, demonstrated by earlier improvement of the peroneal functional index, stronger muscle contractile function, greater muscle weight, and higher density of regenerated axons compared with unrepaired nerves; (b) removal of the epineurium of the donor nerve at the nerve coaptation site increases the effectiveness of end‐to‐side neurorrhaphy, but the epineurium appears to be a partial barrier to axonal regeneration; (c) removal of the epineurium does not affect the structure and function of the donor nerve; and (d) end‐to‐end repair achieved the best functional recovery among the four groups; therefore, end‐to‐side repair should be considered as a potential alternative only when no proximal nerve is available.
Expression of leukemia inhibitory factor by cartilage‐forming tumors of bone: An immunohistochemical study
Authors: Gouin Francois , Moreau Anne , Couillaud Séverine , Guicheux Jérôme , Passuti Norbert , Godard Anne , Heymann Dominique
Published: February 2005

Recent studies have implicated leukemia inhibitory factor in connective‐tissue metabolism involving the remodeling of bone and the destruction of cartilage tissue. This cytokine, which has also been implicated in the proliferation of solid tumor, is expressed by osteotropic tumor cell lines. The present study investigated the presence of leukemia inhibitory factor in cartilage tissue harvested from cartilage‐forming bone tumors. Immunohistochemical study showed that it was present in all benign enchondromas (n = 8) and malignant chondrosarcomas (n = 6) but not in control tissue (n = 3). The cytokine was localized in only cytoplasmic areas of cartilage cells. The number of stained cells ranged from less than 5% in enchondroma of the hand to more than 70% in grade‐III chondrosarcoma. Moreover, high levels of leukemia inhibitory factor were found in the primary culture of tumor tissues (n = 7). These results question the significance of leukemia inhibitory factor in tumor‐associated bone resorption and the potential role of this cytokine as a prognostic marker.
Mixed‐mode fracture toughness of the cobalt‐chromium alloy/polymethlymethacrylate cement interface
Authors: Mann Kenneth A. , Bhashyam Srinivas
Published: February 2005

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