bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of cisplatin chemotherapy on extracortical tissue formation in canine diaphyseal segmental replacement
Authors: Young David R. , Shin Lih‐Yuann , Rock Michael G. , Frassica Frank J. , Virolainen Petri , Chao Edmund Y. S.
Published: February 2005

The reconstruction of large bone and joint defects after the resection of malignant tumors remains a major challenge. Chemotherapy has significantly lowered the risk of metastasic disease, but complications associated with reconstructive techniques continue to result in late morbidity. In the present study, biomechanical torsion testing, gait analysis, and histomorphometric and scanning electron microscopic evaluations of 24 dogs were used to examine the effects of preoperative and postoperative administration of cisplatin on the biologic fixation of a porous‐coated segmental replacement prosthesis. The chemotherapy consisted of four cycles of cisplatin administered at a dosage of 75 mg/m:2 preoperatively or postoperatively. The healing was enhanced by use of an autogenous corticocancellous bone graft. The graft was placed evenly around the prosthesis and the adjacent femoral cortex. Mechanical analyses of torsional stiffness, yield strength, and maximum strength revealed no statistically significant differences between the groups at 12 weeks. Such lack of difference was mainly due to the penetration of highly organized fibrous tissue into the porous surface; this provided strong fixation of the implant to bone even in the absence of bone ingrowth. Although bone ingrowth into the prostheses was not affected, electron microscopic, histomorphometric, and radiologic analyses showed a clear difference in the formation of new bone around the prosthesis. Preoperative chemotherapy did not alter the formation of new bone, but specimens from animals treated postoperatively with cisplatin showed significantly less bone graft resorption and less new bone formation. Hence, the effect of cisplatin administration caused only a temporary delay, not a permanent effect, on extracortical capsule formation. The formation of extracortical bone and soft tissue might prevent debris‐incised osteolysis and, therefore, prevent late complications by forming a tight capsule around the bone‐prosthetic interface.
Dependence of trabecular damage on mechanical strain
Authors: Wachtel Edward F. , Keaveny Tony M.
Published: February 2005

Trabecular damage may play a role in hip fracture, bone remodeling, and prosthesis loosening. We hypothesized that when trabecular bone is loaded beyond its elastic range, both the type and the amount of damage depend on the applied strains. Thirty specimens of trabecular bone from the bovine tibia underwent compression tests to one of three levels of strain (0.4,1.0, and 2.5%) (n = 10 per group). The 0.4% level was a mechanically nondestructive control group that accounted for any systematic errors. Optical microscopy at magnifications as high as × 200 was then used to quantify the trabecular damage for each group. The amount of damage in the yield group (1.0% strain) did not differ from that in the control group (p = 0.66), whereas damage in the post‐ultimate strain group (2.5% strain) increased more than 3‐fold (p < 0.0008). Four types of damage were observed: transverse cracks, shear bands, parallel cracks, and complete fractures, of which the first two were dominant. These findings therefore indicate that damage occurs within trabeculae at yield. By comparison with our previous work, it can also be concluded that substantial modulus reductions in trabecular bone (as much as 60%) are caused by damage primarily within trabeculae. The ability to detect such damage clinically may improve in vivo estimates of whole‐bone strength by identifying regions of densito metrically normal but mechanically compromised trabecular bone.
Temporal and spatial expression of transforming growth factor‐β in the healing patellar ligament of the rat
Authors: Natsuume Takashi , Nakamura Norimasa , Shino Konsei , Toritsuka Yukiyoshi , Horibe Shuji , Ochi Takahiro
Published: February 2005

We investigated the temporal and spatial expression of transforming growth factor‐β in the healing patellar ligament of the rat by immunohistochemistry. The mid‐portion of the medial half of the patellar ligament in 14‐week‐old male Wistar rats was cut transversely with a scalpel. On day 1 after ligament injury, diffuse staining for transforming growth factor‐β was observed in the extracellular matrix filling the wound, and the staining in the adjacent ligament tissue was as weak as it was in the normal ligament. On day 3, the intensity of the diffuse extracellular staining decreased, and the staining was observed in correspondence with the cellular distribution in the wound site and in the adjacent uninjured ligament tissue. On day 7, the intense staining was widely distributed over the whole length of the ligament tissue. On day 28, the staining for transforming growth factor‐β was still observed at the wound site and in the adjacent uninjured ligament tissue, where the staining was reduced in intensity but still stronger than it was in the normal ligament. On day 56, the expression of transforming growth factor‐β was still detectable at the wound site: however, in the adjacent uninjured ligament tissue, it had almost subsided to the normal level. The results of the present study suggest that ligament healing may be accompanied by extensive changes in the expression of transforming growth factor‐β over the whole length of ligament tissue.
Fibre type characteristics of the lumbar paraspinal muscles in normal healthy subjects and in patients with low back pain
Authors: Mannion Anne F. , Weber Barbara R. , Dvorak Jiri , Grob Dieter , Müntener Markus
Published: February 2005

A knowledge of the alteration in the fibre type profile of paraspinal muscle associated with low back pain is essential for the design of successful rehabilitation programmes. In attempting to compare the muscles of patients with low back pain with those of controls, few previous studies have considered factors such as gender, age, and size of the subjects, each of which can potentially confound interpretation of the results. We obtained samples of lumbar paraspinal muscle during spinal surgery from 21 patients with low back pain and, using the percutaneous biopsy technique, from 21 control volunteers matched for gender, age, and body mass. The samples were subject to routine histochemicsl typcal analysis to determine characteristics of muscle fibre type. Compared with controls, the muscle of the patients had a significantly higher proportion of type‐IIB (fast‐twitch glycolytic) fibres than type‐ I (slow oxidatve) fibres. The mean size of a given fibre type did not differ between the patients and the controls. Consequently, the relative area of the muscle iccupied by type‐IIB fibres was higher and that by type‐I fibres Was lower in the patients. The patients had a greater number of muscle samples with more than 1% type‐IIC fibres, and abnormalities that could be described as pathological were more marked in the patients than in the controls. In conclusion, the paraspinal muscles of patients who have low back pain display a more glycolytic (faster) profile; this can be expected to render them less resistant to fatigue.
Staphylococcal septic arthritis: Antibiotic and nonsteroidal anti‐inflammatory drug treatment in a rabbit model
Authors: Smith R. Lane , Kajiyama G. , Schurman D. J.
Published: February 2005

This study evaluated the effects of combining antibiotic therapy with the application of a nonsteroidal anti‐inflammatory drug on the degradation of articular cartilage for an animal model of Staphylococcal septic arthritis. Rabbits were infected intra‐articularly with Staphylococcus aureus. Antibiotic treatment started 18 hours after infection and continued for 7 days. Treatment with the nonsteroidal anti‐inflammatory drug naproxen sodium started 24 hours before infection and continued for either 3 or 7 weeks. The cartilage matrix of uninfected and infected knees was quantified by analysis of glycosaminoglycan and collagen content. Three weeks after infection, the combined treatment of the nonsteroidal anti‐inflammatory drug and antibiotics reduced the loss of glycosaminoglycan and collagen from the cartage of the infected knee by 15 and 30%, respectively, compared with antibiotic treatment alone. Continuing treatment with naproxen sodium for 7 weeks reduced the loss of collagen by 50% when compared with antibiotic treatment alone. The longer period of treatment with naproxen sodium showed little further effect on the loss of glycosaminoglycan than that observed for the 3‐week treatment. Treatment with this drug and antibiotics reduced swelling of the knee and levels of prostaglandin E2 in the synovial fluid. The data support the hypothesis that decreasing post‐infectious inflammation by adding the drug to a standard antibiotic regimen reduces cartilage damage from Staphylococcal septic arthritis.
Prognostic relevance of C‐myc gene expression in giant‐cell tumor of bone
Authors: Gamberi Gabriella , Benassi M. Serena , Böhling Tom , Ragazzini Paola , Molendini Lara , Sollazo M. Rosa , Merli Mara , Ferrari Cristina , Magagnoli Giovanna , Bertoni Franco , Picci Piero
Published: February 2005

Giant‐cell tumor is a primary bone tumor, of uncertain origin, with the potential capacity to metastasize. To study the role of c‐myc and c‐fos oncogene overexpression in the tumorigenesis and metastatic spread of giant‐cell tumors. 32 primary tumors were collected: of these. 19 remained disease‐free and 13 metastasized to the lung. Samples of lung metastasis from these 13 patients were also available for study. The expression of c‐myc and c‐fos mRNA was studied by reverse transcription‐polymerase chain reaction and by in situ hybridization. The expression of protein was studied by Western blot analysis and by immunohistochemistry. C‐myc mRNA was overexpressed in 12 (38%) of the 32 primary tumors. Thirteen primary tumors metastasized to the lung: in nine (69%) of these. c‐myc mRNA was overexpressed. The c‐myc protein was overexpressed in seven (54%) of the 13 tumors that metastasized to the lung. C‐fos was overexpressed in only one lung metastasis. A strong correlation between the overexpression of c‐myc and the occurrence of metastases was found: thus, c‐myc seems a powerful prognosticator in giant‐cell tumor. C‐myc was overexpressed both in giant cells and in mononuclear cells, suggesting that both cell types are involved in the progression of this tumor.
Role of glutathione in cisplatin resistance in osteosarcoma cell lines
Authors: Komiya S. , Gobhardt M. C. , Mangham D. C. , Inoue A.
Published: February 2005

This study was designed to examine whether and how glutathione and catalase increase the resistance of osteosarcoma cells to the toxicity of cisplatin. Eight osteosarcoma cell lines were exposed to varying concentrations of cisplatin. and a [3H]thymidine incorporation study then estimated their drug sensitivity. Cells were pretreated with aminotriazole and buthionine sulfoximine to depress catalase and glutathione activities and then entered into the same protocol to assess their sensitivity to cisplatin. Intracytoplasmic levels of catalase and glutathione were measured before and after the treatments. Cisplatin‐glutathione conjugates were created to examine how glutathione might depress the toxicity of cisplatin. Although the cell lines differed in the magnitude of their response to cisplatin, there was a statistical correlation between intrinsic glutathione content and cisplatin resistance. Pretreatment with aminotriazole reduced catalase activity by 84% but did not change the sensitivity to cisplatin. Depletion of glutathione activity by 70% increased the sensitivity of the cells to the cytotoxicity of cisplatin. In addition, cisplatin was detoxified following conjugation with glutathione. The increased sensitization to cisplatin toxicity caused by the depletion of glutathione and cisplatin detoxification after the in vitro reaction of glutathione to cisplatin indicated that the formation of the glutathione‐cisplatin conjugate was an important mechanism in the cellular resistance to cisplatin. These data also demonstrated that catalase activity did not contribute to resistance to cisplatin and suggested that H2O2‐induced oxidative stress did not significantly contribute to the cytotoxicity of cisplatin in osteosarcoma cells.
Relationships between bone morphology and bone elastic properties can be accurately quantified using high‐resolution computer reconstructions
Authors: Van Rietbergen B. , Odgaard A. , Kabel J. , Huiskes R.
Published: February 2005

It would be advantageous if the mechanical properties of trabecular bone could be directly inferred from stereomorphometric parameters. For that purpose, apparent density and mean intercept length, as measures of bone mass and directionality (fabric), are commonly correlated with the elastic characteristics of bone samples, as determined in compression tests. However, complete and accurate relationships have not yet been established in this way. This may be due not only to the occurrence of artifacts in both the stereomorphometric and the mechanical assessments but also to an inherent inadequacy of mean intercept length in characterizing the full mechanical significance of bone architecture or nonhomogeneities in trabecular tissue properties not accounted for in stereomorphometry. In this study, we introduce a computer modeling approach allowing these biases to be eliminated. With use of high‐resolution three‐dimensional computer reconstructions of trabecular bone specimens for stereomorphometry and for microstructural finite element models to simulate mechanical tests, unbiased comparisons become feasible. The purpose was to investigate if accurate and complete relationships can be established in this way. Four different fabric measures were considered: mean intercept length and three volume‐based ones. Compliance matrices were calculated from fabric tensors, with use of the mathematical relationship proposed by Cowin for 29 vertebral whale‐bone specimens. These were correlated with the compliance constants determined directly from the microstructural finite element, model simulation. The nine orthotropic elastic constants of all 29 specimens were well predicted from their stereomorphometric fabric and volume fraction values, with correlation coefficients ranging from R = 0.9934 to O. 9963. When individual compliance components were considered (1/Ei,. 1/Gij, or ‐vij/Ei), correlation coefficients ranged from R = 0.924 to 0.9X2. All four fabric measures performed equally well. It is concluded that volume fraction and fabric measures correlate highly with the apparent elastic properties of bone samples, provided the anisotropy and nonhomgoencity in the elastic properties of the trabecular tissue itself have negligible effects on the apparent propertie Whether this is true for bone in general remains to be seen, as only a subset was analyzed here. These methods, however, can be valuable in similar assessments of other subsets.
Identification of the oim mutation by dye terminator chemistry combined with automated direct DNA sequencing
Authors: Camacho Nancy P. , Dow David , Toledano Talya R. , Buckmeyer Jennifer K. , Gertner Joseph M. , Brayton Corey F. , Raggio Cathleen L. , Root Leon , Boskey Adele L.
Published: February 2005

The homozygous oimloim mouse, a model of moderate‐to‐severe human osteogenesis imperfecta, contains a G‐nucleotide deletion in the Cola‐2 gene (the murine proα2(I) collagen gene) that results in accumulation of α1(I) homotrimer collagen. Although these mice have a distinctive phenotype that includes multiple fractures and deformities, genotyping is necessary to distinguish them from their wildtype (+/+) and heterozygote (oim/+) littermates. In this study, the dye primer and dye terminator chemistry methods, in combination with automated direct DNA sequencing, were compared for accuracy and ease in genotyping. A total of 82 mice from 14 litters were bred and genotyped, this resulted in 18 +/+, 35 oim/+, and 29 oim/oim mice. The dye primer and dye terminator chemistry methods worked equally well for identification of the deletion mutation and thus the genotype of all of the mice. However, the dye terminator method was found to be superior on the basis of the reduced amount of sample handling and reduced quantity of reagent required.
Bonding of cartilage matrices with cultured chondrocytes: An experimental model
Authors: Peretti Giuseppe M. , Randolph Mark A. , Caruso Enzo M. , Rossetti Francesco , Zaleske David J.
Published: February 2005

The capacity of isolated chondrocytes to join separate masses of cartilage matrix was investigated with composites implanted in subcutaneous pouches in nude mice. Slices of articular cartilage were harvested from lambs and were devitalized by cyclic freezing and thawing. The slices were then either co‐cultured with viable allogeneic lamb chondrocytes (experimental) or cultured without such chondrocytes (control). Composites of three slices were constructed with use of fibrin glue and were implanted in nude mice for periods ranging from 7 to 42 days. Bonding of the experimental matrices with viable chondrocytes was achieved at 28 and 42 days, as assessed by direct examination, histology, thymidine uptake, and fluorescence. No bonding occurred in the control composites without viable chondrocytes. We conclude that devitalized cartilage matrix is a scaffold to which isolated chondrocytes can attach and begin to repopulate.
Spatial and temporal expression of CD44 isoforms in the developing and growing joints of the rat limb
Authors: Noonan Kenneth J. , Reiter Rebecca S. , Kurriger Gail L. , Martin James A. , Maynard Jerry A. , Stevens Jeff W.
Published: February 2005

Hyaluronan is an integral component of proteoglycan‐rich extracellular matrices such as hyaline cartilage. Hyaluronan is commonly found in embryonic tissue and is important in the formation of hydrated matrices that allow cellular expansion and migration. Cell surface hyaluronan‐binding proteins such as CD44 are presumed to be important in the cellular interactions with hyaluronan in both of these processes. The primary aim of this study was to document the spatial and temporal expressions of CD44 isoforms during the development and growth of the diarthrodial joints of rat limbs. With use of in situ hybridization and immunohistochemistry, the CD44s isoform is selectively identified as localized to a single cell layer on opposing sides of the joint at the first appearance of joint cavitation (on the 18th day of gestation). After joint formation in the neonate, the expression of the CD44s isoform in the cells at the joint surface is lost. These findings suggest that the CD44s isoform has a role in the development of the diarthrodial joint, presumably through interaction with hyaluronan.
Fingertip loading and carpal tunnel pressure: Differences between a pinching and a pressing task
Authors: Keir Peter J. , Bach Joel M. , Rempel David M.
Published: February 2005

Carpal tunnel syndrome may be caused by repeated or sustained elevated carpal tunnel pressure. This study examined the relationship between carpal tunnel pressure, posture, and fingertip load. In 20 healthy individuals, carpal tunnel pressure was measured with a catheter inserted into the carpal tunnel of the dominant hand and connected to a pressure transducer. With the wrist in a pressure‐neutral position, the subjects pressed on a force transducer with the index finger to levels of 0, 5, 10, and 15 N. They then pinched the transducer at the same levels of force. For both fingertip‐loading postures, the carpal tunnel pressure increased with increasing fingertip load. Carpal tunnel pressures were significantly greater (p < 0.015) for the pinching task (14.2, 29.9, 41.9, and 49.7 mm Hg [1.89, 3.99, 5.59, and 6.63 kPa] for 0, 5, 10, and 15 N force levels, respectively) than for simple finger pressing (7.8, 14.1, 20.0, and 33.8 mm Hg [1.04, 1.88, 2.67, and 4.51 kPa]). This study indicates that although the external load on the finger remained constant between the two tasks, the internal loading, as measured by carpal tunnel pressure, experienced a near 2‐fold increase by using a pinch grip. These findings should be given consideration in designing work tasks and tools because relatively low fingertip forces, especially in a pinch grip, elevate carpal tunnel pressures to levels that, if prolonged, may lead to the development or exacerbation of carpal tunnel syndrome.
Programmed removal of chondrocytes during endochondral fracture healing
Authors: Lee Francis Young‐In , Choi Yong Won , Behrens Fred F. , DeFouw David O. , Einhorn Thomas A.
Published: February 2005

This investigation tested the hypothesis that the removal of chondrocytes during endochondral fracture healing involves an ordered process of programmed cell death. To accomplish this, unilateral closed fractures were created in the femora of 36 Sprague‐Dawley rats. The rats were killed in groups of four on days 1, 3, 7, 14, 21, 28, 42, 49, and 56 after fracture. The femora were embedded in paraffin and tested for expression of specific markers of fragmented DNA with use of a terminal deoxyuridyl transferase‐mediated deoxyuridine triphosphatebiotin nick end labeling (TUNEL) technique. To determine the potential for trans–differentiation of chondrocytes to osteoblasts calluses were also hybridized to detect expression of osteocal in mRNA. Cell proliferation was assessed by an immunohistochemical detection method for proliferating cell nuclear antigen. A separate group of four rats was killed on day 28 to represent the later stage of the endochondral ossification, and the calluses were examined for cellular morphology with transmission electron microscopy. The results showed a coordination in both time and space of the activities of cellular proliferation and programmed cell death. Cell proliferation was most active in the earlier phases of fracture healing (days 1 through 14) although TUNEL expression was apparent in hypertrophic chondrocytes on day 14 after fracture and persisted until day 28. In the later stages of fracture healing (days 14 through 28), proliferating cell nuclear antigen was no longer synthesized in hard callus (intramembranous bone) and cell removal was the dominant activity in soft callus chondrocytes. Expression of osteocalcin mRNA was detected in osteoblasts but not in hypertrophic chondrocytes or in any other nonosteoblastic cell type. These findings support the hypothesis that the removal of chondrocytes during endochondral fracture healing is part of an ordered transition of tissue types in which the cellular mechanisms are genetically programmed to involve proliferation, maturation, and apoptotic cell death.
Bone regeneration by implantation of purified, culture‐expanded human mesenchymal stem cells
Authors: Bruder Scott P. , Kurth Andreas A. , Shea Marie , Hayes Wilson C. , Jaiswal Neelam , Kadiyala Sudha
Published: February 2005

Bone marrow contains a population of rare progenitor cells capable of differentiating into bone, cartilage, tendon, and other connective tissues. These cells, referred to as mesenchymal stem cells, can be purified and culture‐expanded from animals and humans and have been shown to regenerate functional tissue when delivered to the site of musculoskeletal defects in experimental animals. To test the ability of purified human mesenchymal stem cells to heal a clinically significant bone defect, mesenchymal stem cells isolated from normal human bone marrow were culture‐expanded, loaded onto a ceramic carrier, and implanted into critical‐sized segmental defects in the femurs of adult athymic rats. For comparison, cell‐free ceramics were implanted in the contralateral limb. The animals were elthanized at 4, 8, or 12 weeks, and healing bone defects were compared by high‐resolution radiography, immunohistochemistry, quantitative histomorphometry, and biomechanical testing. In mesenchymal stem cell‐loaded samples, radiographic and histologic evidence of new bone was apparent by 8 weeks and histomorphometry demonstrated increasing bone formation through 12 weeks. Biomechanical evaluation confirmed that femurs implanted with mesenchymal stem cell‐loaded ceramics were significantly stronger than those that received cell‐free ceramics. These studies demonstrate that human mesenchymal stem cells can regenerate bone in a clinically significant osseous defect and may therefore provide an alternative to autogenous bone grafts.
In vitrodifferentiation of chick embryo bone marrow stromal cells into cartilaginous and bone‐like tissues
Authors: Martin Ivan , Padera Robert F. , Vunjak‐Novakovic Gordana , Freed Lisa E.
Published: February 2005

Bone marrow stromal cells, progenitor cells involved in repair of bone and cartilage, can potentially provide a source for autologous skeletal tissue engineering. We investigated which factors were required to inducein vitrodifferentiation of avian bone marrow stromal cells into three‐dimensional cartilaginous and bone‐like tissues. Bone marrow stromal cells from embryonic chicks were expanded in monolayers, seeded onto biodegradable polyglycolic acid scaffolds, and cultured for 4 weeks in orbitally mixed Petri dishes. Cell‐polymer constructs developed an organized extracellular matrix containing glycosaminoglycans and collagen, whereas control bone marrow stromal cell pellet cultures were smaller and consisted predominantly of fibrous tissue. Bone marrow stromal cells expanded with fibroblast growth factor‐2 and seeded onto polymer scaffolds formed highly homogeneous three‐dimensional tissues that contained cartilage‐specific molecular markers and had biochemical compositions comparable with avian epiphyseal cartilage. When cell‐polymer constructs were cultured in the presence of beta‐glycerophosphate and dexamethasone, the extracellular matrix mineralized and bone‐specific proteins were expressed. Our work shows that cell expansion in the presence of fibroblast growth factor‐2 and cultivation on a three‐dimensional polymer scaffold allows differentiation of chick bone marrow stromal cells into three‐dimensional cartilaginous tissues. In thein vitrosystem studied, the same population could be selectively induced to regenerate either cartilaginous or bonelike tissue.
Correlation between biomechanical and structural changes during the regeneration of skeletal muscle after laceration injury
Authors: Kääriäinen Minna , Kääriäinen Janne , Järvinen Teppo L. N. , Sievänen Harri , Kalimo Hannu , Järvinen Markku
Published: February 2005

A standardized and reliable model for muscle laceration injuries was developed. The biomechanical and morphological changes during the process of muscle repair after injury were analysed, and the reproducibility of the methods was evaluated. The soleus muscles of Sprague‐Dawley rats were completely transected and were allowed to heal for 5, 7, 10, 14, 21, 28, or 56 days, when the muscles either were pulled to failure to measure different parameters of tensile strength or were removed for morphological analysis. During the repair process, the regenerating myofibers penetrated into the connective‐tissue scar and formed new myotendinous junctions, thus restoring the functional continuity across the muscle stumps. The muscle atrophied significantly during the recovery period. Mechanical failure occurred in the scar until day 10, and thereafter it occurred within myofibers. Until day 10, the failure load, strain, and specific energy increased to as much as 46.59. and 36% of the control level, respectively: thereafter, there were only minor changes. Stress (tensile strength per cross‐sectional area) reached 86% of the control level by day 21 and further increased to as much as 96% of the control level until day 56. These results indicate that the scar becomes stronger than muscle within 14 days: thereafter, the weakest point is the atrophic muscle. The fact that the stress value was most rapidly normalized suggests that, qualitatively, the regenerated muscle had virtually regained its pretrauma strength by day 56 and that the low values of failure load, strain, and specific energy were mainly due to atrophy of the muscle. Thus, further increase in the tensile strength of the regenerated muscle‐tendon unit may require active exercise to reverse muscle atrophy.
Chondrocytes in culture produce a mechanically functional tissue
Authors: Fedewa Michelle M. , Oegema Theodore R. , Schwartz Michael H. , MacLeod Adrienne , Lewis Jack L.
Published: February 2005

A mechanically testable tissue was grown in vitro from rabbit chondrocytes that were initially plated at high density (approximately 80.000 cells/cm2). The DNA, collagen, and proteoglycan content, as well as the tissue thickness, tensile stiffness, and synthesis rates, were measured at 4, 6, and 8 weeks. The biochemical properties were similar to those for immature cartilage, with predominantly type‐II collagen produced; this indicated that the cells retained their chondrocytic phenotype. The tissue formed a coherent mechanical layer with testable tensile stiffness as early as 4 weeks. The tensile elastic modulus reached 1.3 MPa at 8 weeks, which is in the range of values for native cartilage from the midzone. Collagen density was approximately 24 mg/ml at 8 weeks, which is about one‐half the value for native cartilage, and the collagen fibril diameters were smaller. Chondrocytes in culture responded to culture conditions and were stimulated by cytokine interleukin‐1β. When culture conditions were varied to RPMI nutrient medium with lower fetal bovine serum and higher ascorbic acid concentrations, the thickness decreased and the modulus increased significantly. Interleukin‐1β. added to the 8‐week culture for 2 weeks. caused a decrease of 60% in thickness, a decrease of 81% in proteoglycan content, and a decrease of 31% in collagen content; this is similar to the response of cartilage explants to interleukin‐1β. This cartilage analog may be useful as a model system to study structure‐function relationships in cartilage or as cartilage‐replacement tissue.
Bone morphogenetic protein‐7 in growth‐plate chondrocytes: Regulation by retinoic acid is dependent on the stage of chondrocyte maturation
Authors: Grimsrud Christopher D. , Rosier Randy N. , Puzas J Edward , Reynolds Paul R. , Reynolds Susan D. , Hicks David G. , O'Keefe Regis J.
Published: February 2005

Although the bone morphogenetic proteins stimulate chondrogenesis, little is known regarding their expression and regulation in growth‐plate chondrocytes. The expression of bone morphogenetic protein‐7 was examined in chick growth‐plate chondrocyte cultures. Low basal levels of bone morphogenetic protein‐7 mRNA and protein expression were stimulated by increasing doses of all‐trans retinoic acid, a metabolite of vitamin A. The addition of 10 μM retinoic acid resulted in approximately a 6‐fold increase in bone morphogenetic protein‐7 mRNA levels. In contrast, other growth regulators, including basic fibroblast growth factor, transforming growth factor‐β. vitamin D, bone morphogenetic protein‐6, bone morphogenetic protein‐7, and parathyroid hormone‐related peptide. did not alter bone morphogenetic protein‐7 transcript levels. The increase in bone morphogenetic protein‐7 transcripts, although present at 6 hours, was maximal following a 12‐hour exposure to retinoic acid. Retinoic acid induction of Done morphogenetic protein‐7 transcript levels was dependent on protein synthesis because the induction could be blocked by cyclohexamide. In maturation‐ally distinct subpopulations of chondrocytes separated by countercurrent centrifugal elutriation, retinoic acid markedly induced bone morphogenetic protein‐7 mRNA levels in the least differentiated chondrocytes but had no effect in the most terminally differentiated hypertrophic chondrocytes. Immunohistochemical localization of bone morphogenetic protein‐7 demonstrates its expression throughout the developing and adolescent growth plate consistent with the constitutive pattern of expression seen in isolated chondrocytes. The addition of exogenous bone morphogenetic protein‐7 to chondrocyte cultures stimulated maturation in undif‐ferentiated chondrocyte populations. The data support a role for bone morphogenetic protein‐7 as an autocrine regulator of chondrocyte maturation in the growth plate. Regulation of bone morphogenetic protein‐7 by retinoic acid may be important in normal growth and development as well as in pathologic conditions of an excess or deficiency of vitamin A.
Posterior tilting of the tibial component decreases femoral rollback in posterior‐substituting knee replacement: A computer simulation study
Authors: Piazza Stephen J. , Delp Scott L. , Stulberg S. David , Stern Steven H.
Published: February 2005

Posterior tilting of the tibial component is thought to increase the range of motion in posterior cruciate‐retaining total knee replacement, but its effect on implant motion in posterior cruciate‐substituting total knee replacement is unknown. This issue has become of interest recently because manufacturers have introduced instrumentation that produces a posteriorly tilted tibial cut for both implant types. The purpose of this study was to investigate how motion of posterior cruciate‐substituting total knee replacement is affected when the tibial component is installed with posterior tilt. Sagittal plane implant motions were predicted from prosthesis geometry with use of a computer simulation in which the femoral condyles were assumed to sit in the bottoms of the tibial condylar wells when the knee was in extension. Rollback of the femoral component was produced by a cam‐spine mechanism at higher angles of flexion. The simulations revealed that even small degrees of posterior tilt reduced rollback by limiting the interaction between the cam and spine. Tilting the component posteriorly by 5° caused the cam to contact the spine at a knee flexion angle that was 18° higher than with the untilted component. The results suggest that posterior tilting of the tibial component in posterior cruciate‐substituting knee replacement may not produce the same beneficial effects that have been reported for the tilting of tibial components in posterior cruciate‐retaining knee replacement.
Postural balance measurements for children and adolescents
Authors: Wolff Don R. , Rose Jessica , Jones V. K. , Bloch Daniel A. , Oehlert John W. , Gamble James G.
Published: February 2005

Measurements of standing balance were determined for 92 children and adolescents, 5–18 years old, while they stood on a force plate with eyes open or eyes closed. The measurements included center‐of‐pressure calculations for path length per second, average radial displacement, anterior‐posterior and me‐diolateral amplitudes, area per second, mean frequency of sway, Brownian random motion measure of short‐term diffusion coefficient, and long‐term scaling exponent. All balance parameters improved from youngest to oldest subjects, and the parameters improved when measured with the subjects' eyes open compared with closed. The mean values for data from three trials varied by only 5% when compared with the mean values from 10 trials. Data from this study suggest that force‐plate center‐of‐pressure data can be used to determine differences in standing balance between children and adolescents of different ages and those with movement and balance abnormalities.
Effect of intramedullary polymethylmethacrylate and autogenous cancellous bone on healing of frozen segmental allografts
Authors: Hanson Peter D. , Warner Chad , Kofroth Rachael , Osmond Christian , Bogdanske John J. , Kalscheur Vicki L. , Frassica Frank J. , Markel Mark D.
Published: February 2005

This study was designed to compare bone mineral density, periosteal callus production. new bone formation, bone porosity, histologic appearance, and union of mid‐diaphyseal segmental allografts of the femur stabilized with an interlocking nail technique in a canine model 4 months after the procedure. Anin vivostudy was performed to compare the effects of augmenting interlocking nail fixation with an interlocking nail alone, intramedullary polymethylmethacrylate, intramedullary polymelhylmethacrylate and autogenous cancellous bone applied to the periosteal surface of the host‐allograft junction, autogenous cancellous bone applied to the endosteal surface of the allograft, autogenous cancellous bone applied to the periosteal surface of the host‐allograft junction, and autogenous cancellous bone applied to the periosteal surface of the hostallograft junction and to the endosteal surface of the allograft. There were no differences among treatments for bone mineral density at any time interval. Callus area 4 weeks after the procedure was greater along the lateral and cranial surfaces for treatments with periosteal cancellous bone (p < 0.05). New bone within the allograft segment did not differ among treatments and was reduced compared with the host‐allograft junctions (p < 0.05). The amount and quality of bone tissue at the host‐allograft junctions were greatest with treatments of intramedullary polymethylmethacrylate and autogenous cancellous bonc applied to the periostcal surface of the host‐allograft junction and of autogenous cancellous bone applicd to the periosteal surface of the host‐allograft junction and to the endosteal surface of the allograft (p < 0.05). The rate of bone union was lower, and there was a greater gap (non‐bone tissue) remaining between host and allograft bone with treatment involving just intramedullary polymethylmethacrylate than with other treatments (p < 0.05). The results suggest that augmenting interlocking nail fixation with intramedullary polyrnethylmethacrylate by itself offers no advantage but that a combination of intramedullary polymethylmethacrylate and cancellous bone at the periosteal surface or of cancellous bone within the medullary canal and at the periosteal surface improves the quality of healing at 6 months.
Computed tomography‐based finite element analysis predicts failure loads and fracture patterns for vertebral sections
Authors: Silva Matthew J. , Keaveny Tony M. , Hayes Wilson C.
Published: February 2005

Computed tomography‐based finite element analysis represents a powerful research tool for investigating the mechanics of skeletal fractures. To provide evidence that this technique can be used to predict failure loads and fracture patterns for bone structures, we compared the observed and predicted failure behaviors of 18 midsagittal sections. 10 mm thick, cut from human vertebral bodies. The specimens were scanned by computed tomography, and finite element models were generated with use of empirically determined density‐property relations to assign element‐specific material properties. The specimens were loaded to failure in uniaxial compression, and the models were analyzed under matching conditions. The models provided predictions of yield load that were strongly correlated with experimentally measured values (r2 > 0.86) and were typically within 25% of measured values. Predicted stiffness values were moderately correlated with measured values, but large absolute differences existed between them. Comparisons between regions of observed fracture and of high predicted strain indicated that strain was an accurate indicator of the pattern of local fracture in more than two‐thirds of the bone specimens. In addition, strain contour plots provided better indicators of local fracture than did stress plots in these heterogeneous bone structures. We conclude that computed tomography‐based finite element analysis can be used successfully to predict both global and local failure behavior of simplified skeletal structures.
Surface stiffness affects impact force during a fall on the outstretched hand
Authors: Robinovitch Stephen N. , Chiu James
Published: February 2005

Falls on the outstretched hand are among the most common causes of traumatic bone fracture. However, little is known regarding the biomechanical factors that affect the risk for injury during these events. In the present study, we explored how upper‐extremity impact forces during forward falls are affected by modification of surface stiffness, an intervention applicable to high‐risk environments such as nursing homes, playgrounds, and gymnasiums. Results from both experimental and linear biomechanical models suggest that during a fall onto an infinitely stiff surface, hand contact force is governed by a high‐frequency transient (having an associated peak force Fmax1), followed by a low‐frequency oscillation (having an associated lower magnitude peak force Fmax2). Practical decreases in surface stiffness attenuate Fmax1 but not Fmax2 or the magnitude of force transmitted to the shoulder. Model simulations reveal that this arises from the compliant surface's ability to decrease the velocity across the wrist damping elements at the moment of impact (which governs Fmax1) but inability to substantially reduce the peak deflection of the shoulder spring (which governs Fmax2). Comparison between model predictions and previous data on fracture force suggests that feasible compliant surface designs may prevent wrist injuries during falls from standing height or lower, because Fmax1 will be attenuated and Fmax2 will remain below injurious levels. However, such surfaces cannot prevent Fmax2 from exceeding injurious levels during falls from greater heights and therefore likely provide little protection against upper‐extremity injuries in these cases.
Blunt impact causes changes in bone and cartilage in a regularly exercised animal model
Authors: Newberry William N. , Mackenzie Charles D. , Haut Roger C.
Published: February 2005

The goal of this study was to document the effect of blunt‐impact trauma on the knee in a small animal model that incorporated a known level of physical exercise after impact. We hypothesized that a single blunt impact to the patellofemoral joint, of a magnitude comparable with our earlier studies, would result in degenerative changes to cartilage and to subchondral bone of the patella. Blunt impacts were delivered to rabbit patellofemoral joints without producing bone fracture, and biomechanical and histological analyses were performed on joint tissues at various times. At 12 months, the subchondral bone plate was thicker on the impacted side than on the unimpacted side and than that of the controls at comparable locations (near where surface fissures were found on the impacted side). The instantaneous modulus of cartilage was significantly less on the impacted side than that of controls at 3, 6, and 12 months after impact. The relaxed modulus of cartilage on the unimpacted side increased with time after impact and was significantly greater than that of controls at 12 months. These facts suggest that in this exercise model, the contralateral limb should not be considered a control. The retropatellar cartilage on the impacted side was significantly less thick than that of controls at 12 months, and histological analyses of the cartilage and bone indicated early‐stage osteoarthrosis in the impacted joint. Thus, in this animal model a single subfracture blunt impact produced degeneration of joint tissues.
Retinoic acid responsiveness of cells and tissues in developing fetal limbs evaluated in a RAREhsplacZ transgenic mouse model
Authors: Schroeder Herbert P. von , Heersche Johan N. M.
Published: February 2005

Limb morphogenesis is a complex phenomenon in which retinoids play an important role. Abnormal maternal retinoid levels from high oral doses cause fetal malformations, including abnormalities of the musculoskeletal system. Our purpose was to identify the retinoid‐responsive cells in bone and cartilage during limb development by using a transgenic line of mice containing a reporter gene insert consisting of a retinoic acid response element linked to an Escherichia coli β‐galactosidase gene. Transgenic fetuses from day 11.5 after conception to birth (day 20) were analyzed histologically. Retinoid‐responsive cells and tissues were first seen in the limb bud at 12.5 days in the webs between the forming digits. The webs stained maximally at 14.5 days, after which staining intensity subsided. Staining in the muscles was detectable at 13.5 days, at a stage coinciding with myoblast fusion. Specific regions of perichondrium and periosteum also stained at this Stage. Occasional staining was observed in individual chondroblasts in all chondrogenic regions, including hypertrophic chondroblasts and certain articular surfaces of developing joints. Staining of these tissues decreased in intensity in subsequent stages. Osteoclasts started to express β‐galactosidase at 15.5 days and continued to stain into maturity. Our results indicate that specific subsets of cells respond to retinoids at specific stages in the course of normal limb development. In hypertrophic chondrocytes and cells in the webs and joints that display such a response, retinoid‐induced effects may be linked to cell death that occurs in these regions. Staining in muscle, perichondrium, and periosteum may reflect retinoid‐induced effects associated with cell differentiation and growth. These results suggest that retinoids play a role in a variety of tissues, including bone and cartilage, at specific stages during morphogenesis.
Analytic model to predict the strength of tendon repairs
Authors: Lotz Jeffrey C. , Hariharan Jayaram S. , Diao Edward
Published: February 2005

We developed an analytic model to predict suture load‐sharing immediately after flexor tendon repair in the hand. Tendon repair was mathematically modeled as two nonlinear springs in parallel, representing separate core and peripheral sutures that were in series with a third nonlinear spring representing the tendon. To serve as a basis for, and validation of, our analytic model, fresh human flexor digitorum profundus tendons were harvested and mechanically tested either intact or after surgical repair in a variety of ways: core suture alone, superficial peripheral suture alone, deep peripheral suture alone, core suture plus superficial peripheral suture, and core suture plus deep peripheral suture. The stiffness and strength of the composite repairs predicted with use of the analytic model were comparable with those determined experimentally. Furthermore, the model predicted inequities in suture load‐sharing, with 64% of the applied load carried by the peripheral suture when it was placed superficially, as compared with 77% when the peripheral suture was placed deep. Our results demonstrate a disparity in load‐sharing within composite suture systems, the rectification of which may lead to significant improvement in the repair strength. To this end, we expect that our analytic model will serve as a basis for the design of more efficient, and consequently stronger, suture techniques.
Collagen fiber sliding during ligament growth and contracture
Authors: Wood Mark L. , Lester Gayle E. , Dahners Laurence E.
Published: February 2005

It is hypothesized that the sliding of collagen fibers past one another plays an important role in changes of ligament length during growth or contracture. To explore this possibility, we used the fluorescent dye dichlorotriazinyl fluorescein to stain collagen fibers perpendicular to their orientation in a rat medial collateral ligament model. Growth, contracture, and control models (with rats weighing 50–75 g in the first and 500–600 g in the latter two groups) were studied. In the contracture model, the medial collateral ligament was transected distally. Marking sutures were used to verify the presence of growth or contracture in each medial collateral ligament. Fluorescence photomicrography after 2 weeks demonstrated stained collagen fibers protruding from either side of the original mark as one would expect, in either growth or contracture, if the fibers slid past one another and away from their initial location during changes in length. By measuring the initial and final widths of the growth and contracture model marks and correlating them to controls that had minimal growth (rats grow throughout their life) and were free of contracture, we have provided evidence that collagen sliding plays a significant role in changes in ligament length.