Xu Yang

Hospital for Special Surgery, New York City, New York, United States

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Publications (21)51.74 Total impact

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    ABSTRACT: A calcium phosphate - hydroxyapatite (HA) bone cement was loaded with varying concentrations of tobramycin and vancomycin and the elution properties of these antibiotics were evaluated. Nine groups of antibiotic loaded cement cylinders (N = 6 in each group) were prepared and placed in saline for 28 days. Elution rates of tobramycin and vancomycin from the HA cement were evaluated at high, medium, and low doses of incorporated antibiotic. Tobramycin elution rates did not vary according to dose (0.36, 0.18, and 0.09g). Vancomycin elution rates were also not significantly affected by dose (0.1 , 0.05 , and 0.025 g). The combination of tobramycin and vancomycin increased the elution rate of vancomycin for the medium and low dose of tobramycin. The dose of tobramycin did not affect its elution rate from the cement in the combined groups. Importantly, the concentration of antibiotic eluent stayed above the minimum inhibitory concentration for the entire 28 days for all groups except the medium and low dose of vancomycin alone. Overall, elution rates of both tobramycin and vancomycin in the calcium phosphate-HA cement were comparable to those from polymethylmethacryltate beads in vitro.
    Journal of Biomaterials Science Polymer Edition 05/2013; 24(7):797-806. · 1.70 Impact Factor
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    ABSTRACT: Although mechanical loading is known to influence trabecular bone adaptation, the role of specific loading parameters requires further investigation. Previous studies demonstrated that the number of loading cycles and loading duration modulate the adaptive response of trabecular bone in a rabbit model of applied loading. In the current study, we investigated the influence of load magnitude on the adaptive response of trabecular bone using the rabbit model. Cyclic compressive loads, producing peak pressures of either 0.5 or 1.0 MPa, were applied daily (5 days/week) at 1 Hz and 50 cycles/day for 4 weeks post-operatively to the trabecular bone on the lateral side of the distal right femur, while the left side served as an nonloaded control. The adaptive response was characterized by microcomputed tomography and histomorphometry. Bone volume fraction, bone mineral content, tissue mineral density, and mineral apposition rate (MAR) increased in loaded limbs compared to the contralateral control limbs. No load magnitude dependent difference was observed, which may reflect the critical role of loading compared to the operated, nonloaded contralateral limb. The increased MAR suggests that loading stimulated new bone formation rather than just maintaining bone volume. The absence of a dose-dependent response of trabecular bone observed in this study suggests that a range of load magnitudes should be examined for biophysical therapies aimed at augmenting current treatments to enhance long-term fixation of orthopedic devices. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
    Journal of Orthopaedic Research 02/2013; · 2.88 Impact Factor
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    ABSTRACT: BACKGROUND:Osteoarthritis (OA), a degenerative cartilage disease, results in alterations of the chemical and structural properties of tissue. Arthroscopic evaluation of full-depth tissue composition is limited and would require tissue harvesting, which is inappropriate in daily routine. Fourier transform infrared (FT-IR) spectroscopy is a modality based on molecular vibrations of matrix components that can be used in conjunction with fiber optics to acquire quantitative compositional data from the cartilage matrix. PURPOSE:To develop a model based on infrared spectra of articular cartilage to predict the histological Mankin score as an indicator of tissue quality. STUDY DESIGN:Comparative laboratory study. METHODS:Infrared fiber optic probe (IFOP) spectra were collected from nearly normal and more degraded regions of tibial plateau articular cartilage harvested during knee arthroplasty (N = 61). Each region was graded using a modified Mankin score. A multivariate partial least squares algorithm using second-derivative spectra was developed to predict the histological modified Mankin score. RESULTS:The partial least squares model derived from IFOP spectra predicted the modified Mankin score with a prediction error of approximately 1.4, which resulted in approximately 72% of the Mankin-scored tissues being predicted correctly and 96% being predicted within 1 grade of their true score. CONCLUSION:These data demonstrate that IFOP spectral parameters correlate with histological tissue grade and can be used to provide information on tissue composition. CLINICAL RELEVANCE:Infrared fiber optic probe studies have significant potential for the evaluation of cartilage tissue quality without the need for tissue harvest. Combined with arthroscopy, IFOP analysis could facilitate the definition of tissue margins in debridement procedures.
    The American journal of sports medicine 10/2012; · 3.61 Impact Factor
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    ABSTRACT: Periprosthetic joint infection is a particularly difficult orthopedic problem, complicating a growing number of revision procedures. Joint debridement and systemic antibiotics are the mainstay of treatment, yet difficulty remains in maintaining a minimum inhibitory concentration of antibiotic at the localized site of infection. This study analyzes the elution characteristics of a 40%bwt calcium phosphate-60%bwt calcium sulfate composite, at varying concentrations of vancomycin. Four groups of varying concentrations of vancomycin (2.63%bwt, 5.13%, 9.76%, and 17.78%) were mixed with one pack of the composite cement. At designated time intervals up to 28 days, the antibiotic concentration was detected using fluorescence polarization immunoassay and the elution trends compared. The elution rate of each of the four groups decreased over time. At almost all of the intervals, the elution rates of the higher concentration groups were significantly higher than the lower concentration groups (P < 0.05). Calcium sulfate reabsorbs over a prolonged period, producing porosity which allows for new bone ingrowth through occupation of osteoprogenitor cells and osteoblasts; while calcium phosphate acts as a long-term osteoconductive matrix. The results of this study suggest that vancomycin can be mixed affectively with a calcium sulfate/phosphate composite, both maintaining stability and eluting gradually over a clinically relevant period of time.
    HSS Journal 07/2012; 8(2):129-32.
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    ABSTRACT: OBJECTIVE: Little is known about how the biochemical properties of collagen change during tissue regeneration following cartilage damage. In the current study, temporal changes in cartilage repair tissue biochemistry were assessed in a rabbit osteochondral defect. DESIGN: Bilateral full thickness 3mm osteochondral trochlear groove defects were created in 54 adult male skeletally mature New Zealand white rabbits and tissue repair monitored over 16 weeks. Collagen content, cross-links, lysyl hydroxylation, gene expression, histological grading, and FTIR analyses were performed at 2, 4, 6, 8, 12, and 16 weeks. RESULTS: Defect fill occurred at ~4 weeks post-injury, however, histological grading showed that the repair tissue never became normal, primarily due to the presence of fibrocartilage. Gene expression levels of Col1a1 and Col1a2 were higher in the defect compared to adjacent regions. Collagen content in the repair tissue reached the level of normal cartilage at 6 weeks, but it took 12 weeks for the extent of lysine hydroxylation to return to normal. Divalent immature cross-links markedly increased in the early stages of repair. Though the levels gradually diminished thereafter, they never returned to the normal levels. The mature cross-link, pyridinoline, gradually increased with time and nearly reached normal levels by week 16. Infrared imaging data of protein content paralleled the biochemical data. However, collagen maturity, a parameter previously shown to reflect collagen cross-link ratios in bone, did not correlate with the biochemical determination of cross-links in the repair tissue.. CONCLUSION: Collagen biochemical data could provide markers for clinical monitoring in a healing defect.
    Cartilage 07/2012; 3(3):278-287.
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    ABSTRACT: Enhancing the quantity and quality of cancellous bone with anabolic pharmacologic agents may lead to more successful outcomes of non-cemented joint replacements. Using a novel rabbit model of cancellous bone loading, we examined two specific questions regarding bone formation at the bone-implant interface: (1) does the administration of intermittent PTH, a potent anabolic agent, and mechanical loading individually and combined enhance the peri-implant cancellous bone volume fraction; and, (2) does surgical trauma enhance the anabolic effect of PTH on peri-implant bone volume fraction. In this model, PTH enhanced peri-implant bone volume fraction by 30% in loaded bone, while mechanical loading alone increased bone volume fraction modestly (+10%). Combined mechanical loading and PTH treatment had no synergistic effect on any cancellous parameters. However, a strong combined effect was found in bone volume fraction with combined surgery and PTH treatment (+34%) compared to intact control limbs. Adaptive changes in the cancellous bone tissue included increased ultimate stress and enhanced remodeling activity. The number of proliferative osteoblasts increased as did their expression of pro-collagen 1 and PTH receptor 1, and the number of TRAP positive osteoclasts also increased. In summary, both loading and intermittent PTH treatment enhanced peri-implant bone volume, and surgery and PTH treatment had a strong combined effect. This finding is of clinical importance since enhancing early osseointegration in the post-surgical period has numerous potential benefits.
    Bone 05/2012; · 3.82 Impact Factor
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    ABSTRACT: Unstable implants in bone become surrounded by an osteolytic zone. This is seen around loose screws, for example, but may also contribute to prosthetic loosening. Previous animal studies have shown that such zones can be induced by fluctuations in fluid pressure or flow, caused by implant instability. To understand the roles of pressure and flow, we describe the 3-dimensional distribution of osteolytic lesions in response to fluid pressure and flow in a previously reported rat model of aseptic loosening. 50 rats had a piston inserted in the proximal tibia, designed to produce 20 local spikes in fluid pressure of a clinically relevant magnitude (700 mmHg) twice a day. The spikes lasted for about 0.3 seconds. After 2 weeks, the pressure was measured in vivo, and the osteolytic lesions induced were studied using micro-CT scans. Most bone resorption occurred at pre-existing cavities within the bone in the periphery around the pressurized region, and not under the piston. This region is likely to have a higher fluid flow and less pressure than the area just beneath the piston. The velocity of fluid flow was estimated to be very high (roughly 20 mm/s). The localization of the resorptive lesions suggests that high-velocity fluid flow is important for bone resorption induced by instability.
    Acta Orthopaedica 08/2010; 81(4):508-16. · 2.74 Impact Factor
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    ABSTRACT: Biophysical stimuli may be an effective therapy to counteract age-related changes in bone structure that affect the primary stability of implants used in joint replacement or fracture fixation. The influence of controlled mechanical loading on osseointegration was investigated using an in vivo device implanted in the distal lateral femur of 12 male rabbits. Compressive loads (1 MPa, 1 Hz, 50 cycles/day, 4 weeks) were applied to a porous titanium foam implant and the underlying cancellous bone. The contralateral limbs served as nonloaded controls. Backscattered electron imaging indicated that the amount of bone ingrowth was significantly greater in the loaded limb than in the nonloaded control limb, whereas the amount of underlying cancellous periprosthetic bone was similar. No significant difference in the mineral apposition rate of the bone ingrowth or periprosthetic bone was measured in the loaded compared to the control limb. Histological analysis demonstrated newly formed woven bone in direct apposition to the implant coating, with a lack of fibrous tissue at the implant-periprosthetic bone interface in both loaded and nonloaded implants. The lack of fibrous tissue demonstrates that mechanical stimulation using this model significantly enhanced cancellous bone ingrowth without the detrimental effects of micromotion. These results suggest that biophysical therapy should be further investigated to augment current treatments to enhance long-term fixation of orthopedic devices. Additionally, this novel in vivo loading model can be used to further investigate the influence of biophysical stimulation on other tissue engineering approaches requiring bone ingrowth into both metallic and nonmetallic cell-seeded scaffolds.
    Tissue Engineering Part C Methods 04/2010; 16(6):1399-406. · 4.64 Impact Factor
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    ABSTRACT: Techniques for epiphysiodesis have evolved from open surgical techniques requiring direct observation of the physis to percutaneous techniques performed with fluoroscopy. Our purposes were to (1) describe a new minimally invasive surgical technique used to achieve epiphysiodesis using radiofrequency ablation, (2) document the effect of radiofrequency ablation on tibia length at 2, 6, and 12 weeks after ablation in a skeletally immature rabbit model, and (3) assess the effects of radiofrequency ablation on the histologic appearance of the proximal tibia physis and proximal tibia articular cartilage. We performed epiphysiodesis of the rabbit proximal tibia on 15 skeletally immature male New Zealand White rabbits using a 22-gauge radiofrequency probe. The probe was positioned percutaneously and heated to 90 degrees C for 4 minutes on the medial and lateral (1/2) of the physis. The opposite tibia was used as a control. Five animals were sacrificed at 2, 6, or 12 weeks postoperatively. Tibia length was compared using Faxitron(R) radiographs and electronic calipers. Histology of the growth plate was assessed with light microscopy. We observed differences in tibia length between 4.16 mm and 11.59 mm (average 7.86 mm) at 12 weeks. The proximal tibia physis closed radiographically and histologically in all animals by 12 weeks. Histologic analysis showed no evidence of articular cartilage injury. This technique was reproducible and resulted in bone fusion of the rabbit proximal tibial growth plate. The use of radiofrequency ablation as described in this report may be used as an alternative to other surgical epiphysiodesis techniques. This technique may be useful for epiphysiodesis of small tubular bones of the hands and feet in humans.
    Clinical Orthopaedics and Related Research 03/2010; 468(7):1943-8. · 2.79 Impact Factor
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    ABSTRACT: A novel porous titanium foam implant has recently been developed to enhance biological fixation of orthopaedic implants to bone. The aim of this study was to examine the mechanical and histological characteristics of bone apposition into two different pore sizes of this titanium foam (565 and 464 micron mean void intercept length) and to compare these characteristics to those obtained with a fully porous conventionally sintered titanium bead implant. Cylindrical implants were studied in a rabbit distal femoral intramedullary osseointegration model at time zero and at 3, 6, and 12 weeks. The amount of bone ingrowth, amount of periprosthetic bone, and mineral apposition rate of periprosthetic bone measured did not differ among the three implant designs at 3, 6, or 12 weeks. By 12 weeks, the interface stiffness and maximum load of the beaded implant was significantly greater than either foam implant. No significant difference was found in the interface stiffness or maximum load between the two foam implant designs at 3, 6, or 12 weeks. The lower compressive modulus of the foam compared to the more dense sintered beaded implants likely contributed to the difference in failure mode. However, the foam implants have a similar compressive modulus to other clinically successful coatings, suggesting they are nonetheless clinically adequate. Additional studies are required to confirm this in weight-bearing models. Histological data suggest that these novel titanium foam implants are a promising alternative to current porous coatings and should be further investigated for clinical application in cementless joint replacement.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 12/2009; 92(2):479-88. · 2.31 Impact Factor
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    ABSTRACT: Mechanical stimuli are critical to the growth, maintenance, and repair of the skeleton. The adaptation of bone to mechanical forces has primarily been studied in cortical bone. As a result, the mechanisms of bone adaptation to mechanical forces are not well-understood in cancellous bone. Clinically, however, diseases such as osteoporosis primarily affect cancellous tissue and mechanical solutions could counteract cancellous bone loss. We previously developed an in vivo model in the rabbit to study cancellous functional adaptation by applying well-controlled mechanical loads to cancellous sites. In the rabbit, in vivo loading of the lateral aspect of the distal femoral condyle simulated the in vivo bone-implant environment and enhanced bone mass. Using animal-specific computational models and further in vivo experiments we demonstrate here that the number of loading cycles and loading duration modulate the cancellous response by increasing bone volume fraction and thickening trabeculae to reduce the strains experienced in the bone tissue with loading and stiffen the tissue in the loading direction.
    Clinical Orthopaedics and Related Research 06/2009; 467(8):2000-6. · 2.79 Impact Factor
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    ABSTRACT: Fracture healing requires controlled expression of thousands of genes. Only a small fraction of these genes have been isolated and fewer yet have been shown to play a direct role in fracture healing. The purpose of this study was threefold: (1) to develop a reproducible open femur model of fracture healing that produces consistent fracture calluses for subsequent RNA extraction, (2) to use this model to determine temporal expression patterns of known and unknown genes using DNA microarray expression profiling, and (3) to identify and validate novel gene expression in fracture healing. In the initial arm of the study, a total of 56 wild-type C57BL/6 mice were used. An open, stabilized diaphyseal femur fracture was created. Animals were killed at 1, 5, 7, 10, 14, 21, and 35 days after surgery and the femurs were harvested for analysis. At each time point, fractures were radiographed and sectioned for histologic analyses. Tissue from fracture callus at all stages following fracture yielded reproducibly large amounts of mRNA. Expression profiling revealed that genes cluster by function in a manner similar to the histologic stages of fracture healing. Based on the expression profiling of fracture tissue, temporal expression patterns of several genes known to be involved in fracture healing were verified. Novel expression of multiple genes in fracture callous tissue was also revealed including leptin and leptin receptor. In order to test whether leptin signaling is required for fracture repair, mice deficient in leptin or its receptor were fractured using the same model. Fracture calluses of mice deficient in both leptin or leptin receptor are larger than wild-type mice fractures, likely due to a delay in mineralization, revealing a previously unrecognized role of leptin signaling in fracture healing. This novel model of murine fracture repair is useful in examining both global changes in gene expression as well as individual signaling pathways, which can be used to identify specific molecular mechanisms of fracture healing.
    HSS Journal 09/2008; 4(2):149-60.
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    ABSTRACT: Interaction between wear particle debris and the cells at the implant-bone interface is an important contributory factor to periprosthetic bone loss seen in arthroplasties. To investigate the effect of this particle-induced response on different stages of osteoclast maturation, polymethylmethacrylate (PMMA) particles were added to a murine osteoclastogenic bone marrow cell culture system at either day 0, day 4, or day 8 of culture, which represented PMMA particle stimulation of precursor osteoclasts, mature osteoclasts, or end-stage osteoclasts, respectively. The number of TRAP-posi-tive multinucleate cells (MNCs) and the degree of bone resorption in culture were measured Treatment of precursor osteoclasts with PMMA particles resulted in a statistically significant increase in TRAP-positive MNCs that persisted for 4 days, but there was no significant increase in bone resorption. Addition of particles to mature osteoclasts resulted in a significant increase in the number of TRAP-positive MNCs that lasted for 8 days, and also a significant increase in bone resorption. Treatment of end-stage osteoclasts with PMMA particles did not result in an increased number of TRAP-positive MNCs and there was no increase in bone resorption. Treatment of mature osteoclasts with PMMA particles resulted in an elevated number of TRAP-positive cells. This persisted over a longer period of time than at the other stages of osteoclast development, and there was also a greater increase in bone resorption.
    Acta Orthopaedica 05/2008; 79(2):281-8. · 2.74 Impact Factor
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    ABSTRACT: Currently, the standard treatment for osteogenesis imperfecta (OI) is bisphosphonate therapy. Recent studies, however, have shown delayed healing of osteotomies in a subset of OI patients treated with such agents. The current study sought to determine the effects of another therapy, RANKL inhibition, on bone healing and bone strength in the growing oim/oim mouse, a model of moderate to severe OI. Mice [73 oim/oim and 69 wild-type (WT)] were injected twice weekly with either soluble murine RANK (RANK-Fc) (1.5 mg/kg) or saline beginning at 6 weeks of age. At 8 weeks of age, the animals underwent transverse mid-diaphyseal osteotomies of the right femur. Therapy was continued until sacrifice at 2, 3, 4, or 6 weeks postfracture. At 6 weeks post-fracture, greater callus area (6.59 +/- 3.78 mm(2) vs. 2.67 +/- 2.05 mm(2), p = 0.003) and increased radiographic intensity (mineral density) (0.48 +/- 0.14 vs. 0.30 +/- 0.80, p = 0.005) were found in the RANK-Fc versus saline oim/oim group, indicating a delay in callus remodeling. Despite this delay, mechanical tests at 6 weeks postfracture revealed no significant differences in whole bone properties of stiffness and failure moment. Further, RANKL inhibition resulted in a greater failure moment and greater work to failure for the nonfractured contralateral WT bones compared to the nonfractured saline WT bones. Together, these results demonstrate that RANKL inhibition does not adversely affect the mechanical properties of healing bone in the oim/oim mice, and is associated with increased strength in intact bone in the WT mice.
    Journal of Orthopaedic Research 03/2008; 26(2):153-64. · 2.88 Impact Factor
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    ABSTRACT: IL-6 is a pleiotropic cytokine involved in cell signaling in the musculoskeletal system, but its role in bone healing remains uncertain. The purpose of this study was to examine the role of IL-6 in fracture healing. Eight-week-old male C57BL/6 and IL-6 -/- mice were subjected to transverse, mid-diaphyseal osteotomies on the right femora. Sacrifice time points were 1, 2, 4, or 6 weeks post-fracture (N=14 per group). Callus tissue properties was analyzed by microcomputed tomography (micro-CT) and Fourier transform infrared imaging spectroscopy (FT-IRIS). Cartilage and collagen content, and osteoclast density were measured histologically. In intact unfractured bone, IL-6 -/- mice had reduced crystallinity, mineral/matrix ratio, tissue mineral density (TMD), and bone volume fraction (BVF) compared to wildtype mice. This suggests that there was an underlying deficit in baseline bone quality in IL-6 -/- mice. At 2 weeks post-fracture, the callus of IL-6 -/- mice had reduced crystallinity and mineral/matrix ratio. These changes were less evident at 4 weeks. At 2 weeks, the callus of the IL-6 -/- mice had an increased tissue mineral density (TMD), an increased cartilage and collagen content, and reduced osteoclast density compared to these parameters in wildtype mice. By 4 and 6 weeks, these parameters were no longer different between the two strains of mice. In conclusion, IL-6 -/- mice had delayed callus maturity, mineralization, and remodeling compared with the callus of the wildtype mice. These effects were transient indicating that the role of IL-6 appears to be most important in the early stages of fracture healing.
    Bone 01/2008; 41(6):928-36. · 3.82 Impact Factor
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    ABSTRACT: Assessment of subtle changes in proteoglycan (PG) and collagen, the primary macromolecular components of cartilage, which is critical for diagnosis of the early stages of osteoarthritis (OA), has so far remained a challenge. In this study we induced osteoarthritic cartilage changes in a rabbit model by ligament transection and medial meniscectomy and monitored disease progression by infrared fiber optic probe (IFOP) spectroscopy, Fourier transform infrared imaging spectroscopy (FT-IRIS), and magnetic resonance imaging (MRI) microscopy. IFOP studies combined with chemometric partial least-squares analysis enabled us to monitor progressive cartilage surface changes from two to twelve weeks post-surgery. FT-IRIS studies of histological sections of femoral condyle cartilage revealed that compared with control cartilage the OA cartilage had significantly reduced PG content 2 and 4 weeks post-surgery, collagen fibril orientation changes 2 and 4 weeks post-surgery, and changes in collagen integrity 2 and 10 weeks post-surgery, but no significant changes in collagen content at any time. MR microscopy studies revealed reduced fixed charge density (FCD), indicative of reduced PG content, in the OA cartilage, compared with controls, 4 weeks post-surgery. A non-significant trend toward higher apparent MT exchange rate, k(m), was also found in the OA cartilage at this time point, suggesting changes in collagen structural features. These two MR findings for FCD and k(m) parallel the FT-IRIS findings of reduced PG content and altered collagen integrity, respectively. MR microscopy studies of the cartilage at the 12-week time point also found a trend toward longer T (2) values and reduced anisotropy in the deep zone of the OA cartilage, consistent with increased hydration and less ordered collagen. These studies reveal that FT-IRIS and MR microscopy provide complementary data on compositional changes in articular cartilage in the early stages of osteoarthritic degradation.
    Analytical and Bioanalytical Chemistry 04/2007; 387(5):1601-12. · 3.66 Impact Factor
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    ABSTRACT: Significant complications in the management of osteoarthritis (OA) are the inability to identify early cartilage changes during the development of the disease, and the lack of techniques to evaluate the tissue response to therapeutic and tissue engineering interventions. In recent studies several spectroscopic parameters have been elucidated by Fourier transform infrared imaging spectroscopy (FT-IRIS) that enable evaluation of molecular and compositional changes in human cartilage with progressively severe OA, and in repair cartilage from animal models. FT-IRIS permits evaluation of early-stage matrix changes in the primary components of cartilage, collagen and proteoglycan on histological sections at a spatial resolution of approximately 6.25 microm. In osteoarthritic cartilage, the collagen integrity, monitored by the ratio of peak areas at 1338 cm(-1)/Amide II, was found to correspond to the histological Mankin grade, the gold standard scale utilized to evaluate cartilage degeneration. Apparent matrix degradation was observable in the deep zone of cartilage even in the early stages of OA. FT-IRIS studies also found that within the territorial matrix of the cartilage cells (chondrocytes), proteoglycan content increased with progression of cartilage degeneration while the collagen content remained the same, but the collagen integrity decreased. Regenerative (repair) tissue from microfracture treatment of an equine cartilage defect showed significant changes in collagen distribution and loss in proteoglycan content compared to the adjacent normal cartilage, with collagen fibrils demonstrating a random orientation in most of the repair tissue. These studies demonstrate that FT-IRIS is a powerful technique that can provide detailed ultrastructural information on heterogeneous tissues such as diseased cartilage and thus has great potential as a diagnostic modality for cartilage degradation and repair.
    Biochimica et Biophysica Acta 08/2006; 1758(7):934-41. · 4.66 Impact Factor
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    ABSTRACT: Biophysical stimuli are important to the development and maintenance of cancellous bone, but the regulatory mechanisms need to be understood. We investigated the effects of mechanical loading applied in vivo to native cancellous bone in the rabbit on bone formation and trabecular realignment. A novel device was developed to apply controlled compressive loads to cancellous bone in situ. The effect of loading on cancellous bone volume fraction and architecture was quantified. A 4-week experiment was performed in rabbits with devices implanted bilaterally. Cyclic 1 MPa pressures were applied daily to the right limb for 10, 25, or 50 cycles at 0.5 Hz, and the left limb served as the control without any applied loading. Microcomputed tomography and histomorphometry were used to characterize the cancellous tissue within a 4-mm spherical volume located below the loading core. In vivo cyclic loading significantly increased the bone volume fraction, direct trabecular thickness, mean intercept length, and mineral apposition rate in the loaded limbs compared with contralateral limbs. Insufficient evidence was found to demonstrate an effect of number of cycles on the cancellous adaptation between loaded and control limbs. Using a rabbit model, we demonstrated that mechanical loading applied to cancellous bone in situ increased bone formation and altered trabecular morphology. This in vivo model will allow further investigation of cancellous functional adaptation to controlled mechanical stimuli and the influence of mechanical loading parameters, metabolic status, and therapeutic agents.
    Bone 07/2006; 38(6):871-7. · 3.82 Impact Factor
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    ABSTRACT: In vivo identification of early-stage cartilage degradation could positively impact disease progression in osteoarthritis, but to date remains a challenge. The primary goal of this study was to develop an infrared fiber-optic probe (IFOP) chemometric method using partial least squares (PLS1) to objectively determine the degree of cartilage degradation. Arthritic human tibial plateaus (N = 61) were obtained during knee replacement surgery and analyzed by IFOP. IFOP data were collected from multiple regions of each specimen and the cartilage graded according to the Collins Visual Grading Scale of 0, 1, 2, or 3. These grades correspond to cartilage morphology that displayed normal, swelling or softening, superficially slight fibrillation, and deeper fibrillation or serious fibrillation, respectively. The model focused on detecting early cartilage degradation and therefore utilized data from grades 0, 1, and 2. The best PLS1 calibration utilized the spectral range 1733-984 cm(-1), and independent validation of the model utilizing 206 spectra to create a model and 105 independent test spectra resulted in a correlation between the predicted and actual Collins grade of R2 = 0.8228 with a standard error of prediction of 0.258 with a PLS1 rank of 15 PLS factors. A preliminary PLS1 calibration that utilized a cross-validation technique to investigate the possibility of correlation with histological tissue grade (33 spectra from 18 tissues) resulted in R2 = 0.8408 using only eight PLS factors, a very encouraging outcome. Thus, the groundwork for use of IFOP-based chemometric determination of early cartilage degradation has been established.
    Applied Spectroscopy 01/2006; 59(12):1527-33. · 1.94 Impact Factor
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    ABSTRACT: Tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6), pleiotropic cytokines with osteotropic activities, are produced by multiple cells in the skeletal tissue, including macrophages and osteoblasts. They are thought to be pivotally involved in pathological bone resorption, such as that seen with aseptic loosening. Thalidomide is reported to have antiinflammatory, immunomodulatory effects in a number of inflammatory diseases. We investigated the effect of thalidomide on titanium (Ti) particle-induced TNFalpha and IL-6 production by both human macrophage U937 and osteoblast MG-63 cell lines. They were stimulated with 1 x 10(7) Ti particles/ml and treated simultaneously with or without various concentrations of thalidomide (from 2.5 ng/ml to 25 microg/ml) for 24, 48, or 72 h. Cell viability and proliferation were measured. TNFalpha and IL-6 in the supernatant of the culture media were also analyzed with an enzyme-linked immunosorbent assay. We found that with a concentration of thalidomide of less than 2.5 microg/ml the viability of the two cell lines did not differ significantly from that of controls treated simultaneously with 1 x 10(7) Ti particles/ml. Cell proliferation was inhibited to some extent when they were treated with thalidomide 2.5 microg/ml co-cultured with 1 x 10(7) Ti particles/ml. Thalidomide treatment was found to inhibit TNFalpha production in a dose-dependent manner in human macrophages exposed to Ti particles. At the clinically achievable drug dose of 2.5 microg/ml, 34.4% TNFalpha inhibition occurs. Thalidomide had no effect on IL-6 secretion in these cultures. These data support the idea that thalidomide may have potential for treating prosthetic loosening in humans.
    Journal of Orthopaedic Science 02/2003; 8(1):79-83. · 0.96 Impact Factor

Publication Stats

254 Citations
51.74 Total Impact Points

Institutions

  • 2006–2013
    • Hospital for Special Surgery
      • Research Division
      New York City, New York, United States
  • 2012
    • Linköping University
      Linköping, Östergötland, Sweden
  • 2009
    • Cornell University
      • Sibley School of Mechanical and Aerospace Engineering
      Ithaca, New York, United States
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany