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1.
Connect Tissue Res ; 64(2): 175-185, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36318110

RESUMO

OBJECTIVE: Anterior cruciate ligament rupture (ACLR) is a risk factor for the development of post-traumatic osteoarthritis (PTOA). While PTOA in the tibiofemoral joint compartment is well-characterized, very little is known about pathology in the patellofemoral compartment after ACL injury. Here, we evaluated the extent to which ACLR induces early patellofemoral joint damage in a rat model. METHODS: Adult female Lewis rats were randomized to noninvasive ACLR or Sham. Two weeks post-injury, contrast-enhanced micro-computed tomography (µCT) of femoral and patellar cartilage was performed using 20% v/v ioxaglate. Morphometric parameters of femoral trochlear and patellar cartilage, subchondral bone, and trabecular bone were derived from µCT. Sagittal Safranin-O/Fast-Green-stained histologic sections were graded using the OARSI score in a blinded fashion. RESULTS: Cartilage and bone remodelling consistent with an early PTOA phenotype were observed in both femoral trochleas and patellae. ACLR caused osteophyte formation of the patella and pathology in the superficial zone of articular cartilage, including surface fibrillation, fissures, increased cellularity, and abnormal chondrocyte clustering. There were significant increases in thickness of patellar and trochlear cartilage. Loss of subchondral bone thickness, bone volume fraction, and tissue mineral density, as well as changes to patellar and trochlear trabecular microarchitecture, were indicative of catabolic bone remodelling. Several injury-induced changes, including increased cartilage thickness and trabecular spacing and decreased trabecular number were more severe in the patella compared to the trochlea. CONCLUSION: The patellofemoral joint develops mild but evident pathology in the early period following ACL rupture, extending the utility of this model to the study of patellofemoral PTOA.


Assuntos
Lesões do Ligamento Cruzado Anterior , Cartilagem Articular , Osteoartrite , Animais , Feminino , Ratos , Ligamento Cruzado Anterior/patologia , Lesões do Ligamento Cruzado Anterior/complicações , Lesões do Ligamento Cruzado Anterior/patologia , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Osteoartrite/patologia , Ratos Endogâmicos Lew , Microtomografia por Raio-X/efeitos adversos
2.
J Orthop Res ; 39(9): 1965-1976, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33146410

RESUMO

Assess acute alterations in bone turnover, microstructure, and histomorphometry following noninvasive anterior cruciate ligament rupture (ACLR). Twelve female Lewis rats were randomized to receive noninvasive ACLR or Sham loading (n = 6/group). In vivo µCT was performed at 3, 7, 10, and 14 days postinjury to quantify compartment-dependent subchondral (SCB) and epiphyseal trabecular bone remodeling. Near-infrared (NIR) molecular imaging was used to measure in vivo bone anabolism (800 CW BoneTag) and catabolism (Cat K 680 FAST). Metaphyseal bone remodeling and articular cartilage morphology was quantified using ex vivo µCT and contrast-enhanced µCT, respectively. Calcein-based dynamic histomorphometry was used to quantify bone formation. OARSI scoring was used to assess joint degeneration, and osteoclast number was quantified on TRAP stained-sections. ACLR induced acute catabolic bone remodeling in subchondral, epiphyseal, and metaphyseal compartments. Thinning of medial femoral condyle (MFC) SCB was observed as early as 7 days postinjury, while lateral femoral condyles (LFCs) exhibited SCB gains. Trabecular thinning was observed in MFC epiphyseal bone, with minimal changes to LFC. NIR imaging demonstrated immediate and sustained reduction of bone anabolism (~15%-20%), and a ~32% increase in bone catabolism at 14 days, compared to contralateral limbs. These findings were corroborated by reduced bone formation rate and increased osteoclast numbers, observed histologically. ACLR-injured femora had significantly elevated OARSI score, cartilage thickness, and cartilage surface deviation. ACL rupture induces immediate and sustained reduction of bone anabolism and overactivation of bone catabolism, with mild-to-moderate articular cartilage damage at 14 days postinjury.


Assuntos
Lesões do Ligamento Cruzado Anterior , Cartilagem Articular , Doenças Musculoesqueléticas , Osteoartrite , Animais , Lesões do Ligamento Cruzado Anterior/complicações , Lesões do Ligamento Cruzado Anterior/patologia , Remodelação Óssea , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Feminino , Doenças Musculoesqueléticas/patologia , Osteoartrite/patologia , Ratos , Ratos Endogâmicos Lew
3.
Bone ; 137: 115417, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32416288

RESUMO

Micro-computed tomography (µCT) and contrast-enhanced µCT are important tools for preclinical analysis of bone and articular cartilage (AC). Quantitative data from these modalities is highly dependent on the accuracy of tissue segmentations, which are often obtained via time-consuming manual contouring and are prone to inter- and intra-observer variability. Automated segmentation strategies could mitigate these issues, but few such approaches have been described in the context of µCT. Here, we validated a fully-automated strategy for bone and AC segmentation based on registration of an average tissue atlas. Femora from healthy and arthritic rats underwent µCT scanning, and epiphyseal trabecular bone and AC volumes were manually contoured by an expert. Average tissue atlases composed of 1, 3, 5, 10 and 20 pre-contoured training images (n = 10 atlases/group) were generated using iterative shape averaging and registered onto unknown images via affine and non-rigid registration. Atlas-based and expert-defined volumes for bone and AC were compared in terms of shape-based similarity metrics, as well as morphometric and densitometric parameters. Our results demonstrate that atlas-based registrations were capable of highly accurate and consistent segmentation. Atlases built from as few as 3 training images had no incidence of mal-registration and exhibited improved incidence of accurate registration, and higher sensitivity and specificity compared to atlases built from only one training image. Atlas-based segmentation of bone and AC from µCT images is a robust and accurate alternative to manual tissue segmentation, enabling faster, more consistent segmentation of pre-clinical datasets.


Assuntos
Cartilagem Articular , Imageamento por Ressonância Magnética , Algoritmos , Animais , Osso e Ossos , Cartilagem Articular/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Ratos , Sensibilidade e Especificidade , Microtomografia por Raio-X
4.
NPJ Regen Med ; 5: 3, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32133156

RESUMO

Therapeutic approaches requiring the intravenous injection of autologous or allogeneic mesenchymal stromal cells (MSCs) are currently being evaluated for treatment of a range of diseases, including orthopaedic injuries. An alternative approach would be to mobilise endogenous MSCs into the blood, thereby reducing costs and obviating regulatory and technical hurdles associated with development of cell therapies. However, pharmacological tools for MSC mobilisation are currently lacking. Here we show that ß3 adrenergic agonists (ß3AR) in combination with a CXCR4 antagonist, AMD3100/Plerixafor, can mobilise MSCs into the blood in mice and rats. Mechanistically we show that reversal of the CXCL12 gradient across the bone marrow endothelium and local generation of endocannabinoids may both play a role in this process. Using a spine fusion model we provide evidence that this pharmacological strategy for MSC mobilisation enhances bone formation.

5.
Connect Tissue Res ; 61(6): 568-576, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31232119

RESUMO

Objective: Characterize 3D remodeling of the rat intervertebral disc (IVD) following acute annular injury via in vivo micro-computed tomography (µCT), ex vivo contrast-enhanced (CE)-µCT, and histology. Design: Female Lewis rats (N = 4/group) underwent either sham surgery or anterior annular puncture to L3-L4 and L5-L6 (n = 8 IVDs/group) to induce IVD degeneration. Rats were allowed ad libidum cage activity before and after surgery and underwent in vivo µCT scanning at baseline and every 2 weeks post-op for 12 weeks to characterize longitudinal changes in IVD height. At 12 weeks, lumbar spines were dissected and underwent CE-µCT scanning to characterize endpoint glycosaminoglycan distribution and nucleus pulposus (NP) volume ratio. Spines were processed for safranin-O-stained sagittal histology, and IVD degeneration was graded via the Rutges scale. Results: Puncture IVDs exhibited loss of IVD height at all time points from 4 weeks onward compared to Sham-the most severe height loss occurred posteriorly, with significant changes also occurring in the NP and laterally. Puncture IVDs exhibited higher CE-µCT attenuation, indicative of lower glycosaminoglycan content, and reduced NP volume ratio compared to Sham. Histologically, Puncture IVDs had higher Rutges damage scores and exhibited reduced NP cellularity and hydration, disorganized annulus fibrosus (AF) lamellae with evidence of the stab tract, and indistinct AF-NP border compared to Sham. Conclusions: Characterization of the complex, 3D alterations involved in the onset and early progression of IVD degeneration can foster greater understanding of the pathoetiology of IVD degeneration and may inform future studies assessing more sensitive diagnostic techniques or novel therapies.


Assuntos
Anel Fibroso/patologia , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/patologia , Animais , Anel Fibroso/diagnóstico por imagem , Modelos Animais de Doenças , Determinação de Ponto Final , Feminino , Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/diagnóstico por imagem , Ratos Endogâmicos Lew , Coloração e Rotulagem , Microtomografia por Raio-X
6.
J Orthop Res ; 36(10): 2762-2770, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29744917

RESUMO

Quantitative analyses of bone using micro-computed tomography (µCT) are routinely employed in preclinical research, and virtual image reorientation to a consistent reference frame is a common processing step. The purpose of this study was to quantify error introduced by common reorientation algorithms in µCT-based characterization of bone. Mouse and rat tibial metaphyses underwent µCT scanning at a range of resolutions (6-30 µm). A trabecular volume-of-interest (VOI) was manually selected. Image stacks were analyzed without rotation, following 45° In-Plane axial rotation, and following 45° Triplanar rotation. Interpolation was performed using Nearest-Neighbor, Linear, and Cubic interpolations. Densitometric (bone volume fraction, tissue mineral density, bone mineral density) and morphometric variables (trabecular thickness, trabecular spacing, trabecular number, structural model index) were computed for each combination of voxel size, rotation, and interpolation. Significant reorientation error was measured in all parameters, and was exacerbated at higher voxel sizes, with relatively low error at 6 and 12 µm (max. reorientation error in BV/TV was 2.9% at 6 µm, 7.7% at 12 µm and 36.5% at 30 µm). Considering densitometric parameters, Linear and Cubic interpolations introduced significant error while Nearest-Neighbor interpolation caused minimal error, and In-Plane rotation caused greater error than Triplanar. Morphometric error was strongly and intricately dependent on the combination of rotation and interpolation employed. Reorientation error can be eliminated by avoiding reorientation altogether or by "de-rotating" VOIs from reoriented images back to the original reference frame prior to analysis. When these are infeasible, reorientation error can be minimized through sufficiently high resolution scanning, careful selection of interpolation type, and consistent processing of all images. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2762-2770, 2018.


Assuntos
Osso Esponjoso/diagnóstico por imagem , Microtomografia por Raio-X/métodos , Absorciometria de Fóton , Algoritmos , Animais , Camundongos Endogâmicos C57BL , Ratos Endogâmicos Lew
7.
Orthopedics ; 41(3): e376-e382, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29570765

RESUMO

Fresh allograft transplantation of osteochondral defects restores functional articular cartilage and subchondral bone; however, rapid loss of chondrocyte viability during storage and osteoclast-mediated bone resorption at the graft-host interface after transplantation negatively impact outcomes. The authors present a pilot study evaluating the in vitro and in vivo impact of augmenting storage media with bisphosphonates. Forty cylindrical osteochondral cores were harvested from femoral condyles of human cadaveric specimens and immersed in either standard storage media or storage media supplemented with nitrogenated or non-nitrogenated bisphosphonates. Maintenance of graft structure and chondrocyte viability were assessed at 3 time points. A miniature swine trochlear defect model was used to evaluate the influence of bisphosphonate-augmented storage media on in vivo incorporation of fresh osteochondral tissue, which was quantified via µCT and decalcified histology. In the in vitro study, Safranin-O/Fast Green staining showed that both low- and high-dose nitrogenated-treated grafts retained chondrocyte viability and cartilage matrix for up to 43 days of storage. Allografts stored in nitrogenated-augmented storage media showed both µCT and histologic evidence of enhanced in vivo bony and cartilaginous incorporation in the miniature swine trochlear defect model. Several preclinical studies have shown the potential for enhanced storage of fresh osteochondral allografts via additions of relatively common drugs and biomolecules. This study showed that supplementing standard storage media with nitrogenated bisphosphonates may improve maintenance of chondrocyte viability and graft structure during cold storage as well as enhance in vivo osseous and cartilaginous incorporation of the graft. [Orthopedics: 2018; 41(3):e376-e382.].


Assuntos
Conservadores da Densidade Óssea/farmacologia , Transplante Ósseo , Condrócitos/efeitos dos fármacos , Difosfonatos/farmacologia , Fêmur/efeitos dos fármacos , Osseointegração/efeitos dos fármacos , Preservação de Tecido/métodos , Aloenxertos/efeitos dos fármacos , Aloenxertos/fisiologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/transplante , Feminino , Fêmur/transplante , Humanos , Técnicas In Vitro , Masculino , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Distribuição Aleatória , Suínos , Transplante Homólogo
8.
J Orthop Res ; 36(7): 2007-2014, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29314184

RESUMO

Polyethylene wear is a known complication in total joint arthroplasty, however, in vivo wear rates in reverse total shoulder arthroplasty (RTSA) remain largely unknown. This study aimed to quantify volumetric and surface deviation changes in retrieved RTSA humeral liners using a novel micro-computed tomography (µCT)-based technique. After IRB-approval, 32 humeral liners (single manufacturer and model) with term-of-service greater than 90 days were analyzed. Clinical demographics and surgical data were collected via chart review. Unworn liners were used as geometric controls. Retrieved and unworn liners underwent µCT scanning. Retrieved liner volumes were isolated, co-registered to controls of matching geometry, and surface deviations of the articulation surface and rim were computed. Differences in total volume loss (TVL), volumetric wear rate (VWR), and surface deviation were reported. Semi-quantitative grading evaluated rim damage presence and severity. Mean term-of-service for all liners was 2.07 ± 1.33 years (range: 0.30-4.73). Mean TVL and VWR were 181.3 ± 208.2 mm3 and 114.5 ± 160.3 mm3 /year, respectively. Mean articulation and rim surface deviations were 0.084 ± 0.065 and 0.177 ± 0.159 mm, respectively. Articulation surface deviation was positively correlated to term-of-service. Rim damage was present on 63% of liners and correlated significantly to rim surface deviation. This study reports in vivo wear rates of retrieved RTSA implants. Our results demonstrate volumetric and articulation surface wear in select RTSA liners that is correlated to term-of-service. Calculation of in vivo wear rates can help bridge the gap between clinical outcomes and experimental models such as wear simulations and computational models. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2007-2014, 2018.


Assuntos
Artroplastia do Ombro , Polietileno/química , Desenho de Prótese , Falha de Prótese , Ombro/cirurgia , Microtomografia por Raio-X , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Articulações , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Reoperação
9.
J Orthop Res ; 36(7): 2030-2038, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29314237

RESUMO

Mechanical characterization of the intervertebral disc involves labor-intensive and destructive experimental methodology. Contrast-enhanced micro-computed tomography is a nondestructive imaging modality for high-resolution visualization and glycosaminoglycan quantification of cartilaginous tissues. The purpose of this study was to determine whether anionic and cationic contrast-enhanced micro-computed tomography of the intervertebral disc can be used to indirectly assess disc mechanical properties in an ex vivo model of disc degeneration. L3/L4 motion segments were dissected from female Lewis rats. To deplete glycosaminoglycan, samples were treated with 0 U/ml (Control) or 5 U/ml papain. Contrast-enhanced micro-computed tomography was performed following incubation in 40% Hexabrix (anionic) or 30 mg I/ml CA4+ (cationic) for 24 h (n = 10/contrast agent/digestion group). Motion segments underwent cyclic mechanical testing to determine compressive and tensile modulus, stiffness, and hysteresis. Glycosaminoglycan content was determined using the dimethylmethylene blue assay. Correlations between glycosaminoglycan content, contrast-enhanced micro-computed tomography attenuation, and mechanical properties were assessed via the Pearson correlation. The predictive accuracy of attenuation on compressive properties was assessed via repeated random sub-sampling cross validation. Papain digestion produced significant decreases in glycosaminoglycan content and corresponding differences in attenuation and mechanical properties. Attenuation correlated significantly to glycosaminoglycan content and to all compressive mechanical properties using both Hexabrix and CA4+ . Predictive linear regression models demonstrated a predictive accuracy of attenuation on compressive modulus and stiffness of 79.8-86.0%. Contrast-enhanced micro-computed tomography was highly predictive of compressive mechanical properties in an ex vivo simulation of disc degeneration and may represent an effective modality for indirectly assessing disc compressive properties. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2030-2038, 2018.


Assuntos
Degeneração do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/diagnóstico por imagem , Microtomografia por Raio-X , Animais , Fenômenos Biomecânicos , Cartilagem Articular , Meios de Contraste , Feminino , Glicosaminoglicanos , Degeneração do Disco Intervertebral/patologia , Deslocamento do Disco Intervertebral/patologia , Ácido Ioxáglico , Vértebras Lombares , Ratos , Ratos Endogâmicos Lew , Reprodutibilidade dos Testes , Estresse Mecânico
10.
J Shoulder Elbow Surg ; 26(11): 2029-2037, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28893545

RESUMO

BACKGROUND: Larger glenosphere diameters have been used recently to increase prosthesis stability and impingement-free range of motion in reverse total shoulder arthroplasty. The goal of this study was to evaluate the rate of polyethylene wear for 32-mm and 40-mm glenospheres. METHODS: Glenospheres (32 mm and 40 mm, n = 6/group) and conventional polyethylene humeral liners underwent a 5-million cycle (MC) wear simulation protocol. Abduction-adduction and flexion-extension motion profiles were alternated every 250,000 cycles. At each interval, mass loss was determined and converted to volume loss and wear rate. At 0, 2.5 MC, and 5 MC, liners were imaged using micro-computed tomography to determine surface deviation. White light interferometry was performed on liners and glenospheres at 0 and 5 MC to quantify surface roughness. Wear particle morphology was characterized by environmental scanning electron microscopy. RESULTS: Total volume loss was significantly higher in 40-mm liners from 1.5 MC onward (P < .05). Overall, volumetric wear rate was significantly higher in 40-mm liners compared with 32-mm glenospheres (81.7 ± 23.9 mm3/MC vs. 68.0 ± 18.9 mm3/MC; P < .001). However, micro-computed tomography surface deviation results demonstrated increased linear penetration on 32-mm glenospheres compared with 40-mm glenospheres (0.36 ± 0.03 µm vs. 0.28 ± 0.01 µm; P = .002). Surface roughness measurements showed no difference for liners; however, increased roughness was noted for 40-mm glenospheres at 5 MC compared with 32 mm (P < .05). CONCLUSION: Larger glenospheres underwent significantly greater polyethylene volume loss and volumetric wear rates, whereas smaller glenospheres underwent greater polyethylene surface deviations. The enhanced stability provided by larger glenospheres must be weighed against the potential for increased polyethylene wear.


Assuntos
Artroplastia do Ombro , Teste de Materiais , Desenho de Prótese , Falha de Prótese , Prótese de Ombro , Simulação por Computador , Análise de Falha de Equipamento , Humanos , Imageamento Tridimensional , Polietileno , Microtomografia por Raio-X
11.
J Orthop Res ; 35(12): 2755-2764, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28460415

RESUMO

Current imaging-based morphometric indicators of osteoarthritis (OA) using whole-compartment mean cartilage thickness (MCT) and volume changes can be insensitive to mild degenerative changes of articular cartilage (AC) due to areas of adjacent thickening and thinning. The purpose of this preliminary study was to evaluate cartilage thickness-based surface roughness as a morphometric indicator of OA. 3D magnetic resonance imaging (MRI) datasets were collected from osteoarthritis initiative (OAI) subjects with Kellgren-Lawrence (KL) OA grades of 0, 2, and 4 (n = 10/group). Femoral and tibial AC volumes were converted to two-dimensional thickness maps, and MCT, arithmetic surface roughness (Sa ), and anatomically normalized Sa (normSa ) were calculated. Thickness maps enabled visualization of degenerative changes with increasing KL grade, including adjacent thinning and thickening on the femoral condyles. No significant differences were observed in MCT between KL grades. Sa was significantly higher in KL4 compared to KL0 and KL2 in the whole femur (KL0: 0.55 ± 0.10 mm, KL2: 0.53 ± 0.09 mm, KL4: 0.79 ± 0.18 mm), medial femoral condyle (KL0: 0.42 ± 0.07 mm, KL2: 0.48 ± 0.07 mm, KL4: 0.76 ± 0.22 mm), and medial tibial plateau (KL0: 0.42 ± 0.07 mm, KL2: 0.43 ± 0.09 mm, KL4: 0.68 ± 0.27 mm). normSa was significantly higher in KL4 compared to KL0 and KL2 in the whole femur (KL0: 0.22 ± 0.02, KL2: 0.22 ± 0.02, KL4: 0.30 ± 0.03), medial condyle (KL0: 0.17 ± 0.02, KL2: 0.20 ± 0.03, KL4: 0.29 ± 0.06), whole tibia (KL0: 0.34 ± 0.04, KL2: 0.33 ± 0.05, KL4: 0.48 ± 0.11) and medial plateau (KL0: 0.23 ± 0.03, KL2: 0.24 ± 0.04, KL4: 0.40 ± 0.10), and significantly higher in KL2 compared to KL0 in the medial femoral condyle. Surface roughness metrics were sensitive to degenerative morphologic changes, and may be useful in OA characterization and early diagnosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2755-2764, 2017.


Assuntos
Cartilagem Articular/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Idoso , Estudos de Coortes , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade
12.
J Orthop Res ; 35(5): 1067-1075, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27415967

RESUMO

The objective of this study was to quantify and compare the contrast-enhancing properties of the anionic contrast agent ioxaglate/Hexabrix, and cationic contrast agent CA4+ for biochemical and morphological characterization of the intervertebral disc (IVD) via µCT. Optimal contrast agent concentrations were determined by incubating rat lumbar IVDs in dilutions of Hexabrix-320 (20%, 30%, 40%, and 50%) and CA4+ (10, 20, 30, and 40 mg I/ml). µCT imaging was performed at 70 kVp, 114 µA, and 250 ms integration time, 12 µm voxel size. The kinetics of contrast enhancement were quantified with cumulative incubations for 0.5, 1, 2, 12, 16, 20, and 24 h using both agents. Agreement in morphological quantification was assessed via serial scans of the same IVDs. Correlation of attenuation to glycosaminoglycan (GAG) content was determined by enzymatic digestion of IVDs, subsequent µCT imaging, and GAG quantification via dimethylmethylene blue assay. Forty percent Hexabrix and 30 mg I/ml CA4+ were chosen as optimal concentrations. Hexabrix enabled greater delineation of the IVD from surrounding tissues, and CA4+ had the lowest uptake in surrounding soft tissue. Twenty-four hour incubation was sufficient for >99% equilibration of both agents. A high level of agreement was observed in the quantification of IVD volume (ICC = 0.951, r = 0.997) and height (ICC = 0.947, r = 0.991). Both agents exhibited strong linear correlations between µCT attenuation and GAG content (Hexabrix: r = -0.940; CA4+ : r = 0.887). Both agents enable biochemical and morphological quantification of the IVD via contrast-enhanced µCT and are effective tools for preclinical characterization. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1067-1075, 2017.


Assuntos
Meios de Contraste , Etilenodiaminas , Disco Intervertebral/diagnóstico por imagem , Iodobenzenos , Ácido Ioxáglico , Microtomografia por Raio-X , Animais , Feminino , Ratos Endogâmicos Lew
13.
J Biomech ; 49(16): 4159-4163, 2016 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-27863739

RESUMO

Rotator cuff tears are a common shoulder pathology. The rat supraspinatus tendon model is commonly employed for preclinical assessment of rotator cuff pathology or regeneration. However, there is a lack of a standardized biomechanical testing protocol; previous studies have tested the tendon at abduction angles ranging from -15° to 90°. This study aimed to assess the effect of abduction/testing angle on the biomechanical properties of the rat supraspinatus tendon. Fourty-eight shoulders (n=12/group) from healthy Sprague-Dawley rats were randomized to 4 testing angle groups: 0° (corresponding to 90° abduction), 30°, 60°, and 90° (0° abduction). Biomechanical testing of the supraspinatus was performed, consisting of stress-relaxation and load-to-failure. Mechanical properties were calculated, and nonlinear tensile modeling was performed via the Quasilinear Viscoelastic (QLV) and Structurally Based Elastic (SBE) models. Results indicate that testing angle significantly affects supraspinatus tendon biomechanics. Stiffness and modulus significantly decreased with increasing testing angle (stiffness: 20.93±5.8N/mm at 0° vs. 6.12±1.0N/mm at 90°, P<.001; modulus: 59.51±34.0MPa at 0° vs. 22.37±7.4MPa at 90°, P=.002). Testing angle correlated significantly to ultimate strain, yield strain, and all coefficients of the SBE and QLV models, implying differences in collagen fiber crimp patterns and viscoelastic behavior as a function of testing angle. These results suggest that differences in testing methodology, in particular testing angle, significantly affect the measured mechanical properties of the supraspinatus tendon. Future studies may consider utilizing testing angles of 0°-30°, at which tendon stiffness is maximized, and full standardization of rat rotator cuff testing protocols is necessary.


Assuntos
Manguito Rotador/fisiopatologia , Animais , Fenômenos Biomecânicos , Elasticidade , Feminino , Humanos , Amplitude de Movimento Articular , Ratos , Ratos Sprague-Dawley , Lesões do Manguito Rotador/fisiopatologia , Articulação do Ombro/fisiopatologia
14.
Am J Clin Oncol ; 39(1): 76-84, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24351780

RESUMO

The advent of targeted oncolytic agents has created a revolution in the treatment of malignancies. Perhaps best exemplified in myeloproliferative neoplasms (MPN), the tyrosine kinase inhibitors, including inhibitors of BCR-ABL tyrosine kinase and JAK2, have dramatically changed outcomes in persons with MPN. However, clinically relevant dosing of these adenosine triphosphate-mimetic agents in humans leads to inhibition of numerous tyrosine kinases beyond those touted by drug manufacturers and studied in landmark clinical trials. These so-called off-target effects have been linked to both clinical efficacy and toxicity. Rational drug development and serendipitous discovery of drug molecules allows the clinician to select targeted oncolytic agents to treat a specific clinical diagnosis and/or avoid exacerbation of concomitant disease states due to effects upon signaling pathways. Understanding the off-target binding and effects upon signaling pathway of the agents approved for the treatment of MPN will empower the clinician to adroitly select pharmacotherapy, predict toxicities, and utilize these agents in clinical practice for indications beyond MPN.


Assuntos
Antineoplásicos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Janus Quinase 2/antagonistas & inibidores , Transtornos Mieloproliferativos/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Compostos de Anilina/uso terapêutico , Carbazóis/uso terapêutico , Dasatinibe/uso terapêutico , Eosinofilia/tratamento farmacológico , Furanos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Harringtoninas/uso terapêutico , Mepesuccinato de Omacetaxina , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Imidazóis/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Mastocitose/tratamento farmacológico , Nitrilas/uso terapêutico , Policitemia Vera/tratamento farmacológico , Mielofibrose Primária/tratamento farmacológico , Fibrose Pulmonar/tratamento farmacológico , Pirazóis/uso terapêutico , Piridazinas/uso terapêutico , Pirimidinas/uso terapêutico , Quinolinas/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Varíola/tratamento farmacológico , Trombocitemia Essencial/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
15.
J Shoulder Elbow Surg ; 24(9): 1372-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25842031

RESUMO

BACKGROUND: Although short-term outcomes of reverse total shoulder arthroplasty (rTSA) remain promising, the most commonly cited complication remains prosthetic instability. A retentive rTSA liner is commonly used to increase system constraint; however, no studies have evaluated the rate of polyethylene wear. Our hypothesis was that more constrained retentive liners would have higher wear rates than nonretentive liners. METHODS: Six nonretentive and six retentive rTSA non-cross-linked polyethylene liners were subjected to 4.5 million cycles of alternating cycles of abduction-adduction and flexion-extension motion loading profiles. The rTSA liners were assessed for gravimetric wear loss, 3-dimensional volumetric loss by novel micro-computed tomography analysis, and particulate wear debris analysis. RESULTS: Volumetric wear rates were significant at 7 specific time points (1.0, 2.0, 2.5, 3.25, 3.75, 4.0, and 4.5 million cycles) throughout testing between nonretentive and retentive liners; however, overall mean volumetric wear rate was not statistically significant (P = .076). Total volume loss between liner test groups was found to be significant starting after 3.5 million cycles of testing. Maximum and mean surface deviations were found to be larger for retentive liners vs. nonretentive liners by micro-computed tomography analysis across the entire articulation surface. DISCUSSION AND CONCLUSION: Retentive liners undergo significantly greater volume loss and greater surface deviation compared with nonretentive liners, most notably at later time points representing extended implantation times. Additional stability afforded by retentive liners should be balanced against the potential for increased wear and potential for subsequent polyethylene wear-induced aseptic loosening.


Assuntos
Artroplastia de Substituição/instrumentação , Falha de Prótese , Articulação do Ombro , Anatomia Transversal , Materiais Biocompatíveis , Simulação por Computador , Análise de Falha de Equipamento , Humanos , Polietileno , Desenho de Prótese , Articulação do Ombro/cirurgia , Microtomografia por Raio-X
16.
J Shoulder Elbow Surg ; 24(1): 143-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25037062

RESUMO

BACKGROUND: Although short-term outcomes of reverse total shoulder arthroplasty have been promising, long-term success may be limited due to device-specific complications, including scapular notching. Scapular notching has been explained primarily as mechanical erosion; however, the generation of wear debris may lead to further biologic changes contributing to the severity of scapular notching. METHODS: A 12-station hip simulator was converted to a reverse total shoulder arthroplasty wear simulator subjecting conventional and highly cross-linked ultra-high-molecular-weight polyethylene humeral liners to 5 million cycles of alternating abduction-adduction and flexion-extension loading profiles. RESULTS: Highly cross-linked polyethylene liners (36.5 ± 10.0 mm(3)/million cycle) exhibited significantly lower volumetric wear rates compared with conventional polyethylene liners (83.6 ± 20.6 mm(3)/million cycle; P < .001). The flexion-extension loading profile exhibited significantly higher wear rates for conventional (P < .001) and highly cross-linked polyethylene (P < .001) compared with the abduction-adduction loading profile. Highly cross-linked wear particles had an equivalent circle diameter significantly smaller than wear particles from conventional polyethylene (P < .001). CONCLUSIONS: Highly cross-linked polyethylene liners significantly reduced polyethylene wear and subsequent particle generation. More favorable wear properties with the use of highly cross-linked polyethylene may lead to increased device longevity and fewer complications but must be weighed against the effect of reduced mechanical properties.


Assuntos
Artroplastia de Substituição/instrumentação , Prótese Articular , Polietileno , Articulação do Ombro/cirurgia , Artroplastia de Substituição/efeitos adversos , Materiais Biocompatíveis , Análise de Falha de Equipamento , Humanos , Úmero , Prótese Articular/efeitos adversos , Teste de Materiais , Falha de Prótese , Amplitude de Movimento Articular
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