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1.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-34360579

RESUMEN

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.


Asunto(s)
Apoptosis , Proliferación Celular , Hueso Cortical/citología , Epigénesis Genética , Histonas/metabolismo , Complejo Represivo Polycomb 1/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Células Madre/citología , Animales , Ciclo Celular , Diferenciación Celular , Células Cultivadas , Hueso Cortical/lesiones , Hueso Cortical/metabolismo , Daño del ADN , Histonas/genética , Ratones , Ratones Endogámicos C57BL , Complejo Represivo Polycomb 1/genética , Proteínas Proto-Oncogénicas/genética , Transducción de Señal , Células Madre/metabolismo
2.
Medicina (Kaunas) ; 56(2)2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32079310

RESUMEN

BACKGROUND: Osteoporotic spinal fractures commonly occur in elderly patients with low bone mineral density. In these cases, percutaneous vertebroplasty or percutaneous kyphoplasty can provide significant pain relief and improve mobility. However, studies have reported both the recurrence of vertebral compression fractures at the index level after vertebroplasty and the development of new vertebral fractures at the adjacent level that occur without any additional trauma. Pedicle screw fixation combined with percutaneous vertebroplasty has been proposed as an effective procedure for addressing osteoporotic thoracolumbar fractures. However, in osteoporotic populations, pedicle screws can loosen, pullout, or migrate. Currently, the efficacy of cortical bone trajectory screw fixation for osteoporotic fractures remains unclear. Thus, we assessed the effects of using cortical bone trajectory instrumentation with vertebroplasty on patient outcomes. METHOD: We retrospectively reviewed data from 12 consecutively sampled osteoporotic thoracolumbar fracture patients who underwent cortical bone trajectory instrumentation with vertebroplasty. Patients were enrolled beginning in October 2015 and were followed for >24 months. RESULT: The average age was 74 years, and the average dual-energy x-ray absorptiometry T-score was -3.6. The average visual analog scale pain scores improved from 8 to 2.5 after surgery. The average blood loss was 36.25 mL. All patients regained ambulation and experienced reduced pain post-surgery. No recurrent fractures or instrument failures were recorded during follow-up. CONCLUSIONS: Our findings suggest that cortical bone trajectory instrumentation combined with percutaneous vertebroplasty may be a good option for treating osteoporotic thoracolumbar fractures, as it can prevent recurrent vertebral fractures or related kyphosis in sagittal alignment.


Asunto(s)
Hueso Cortical/cirugía , Fracturas por Compresión/cirugía , Osteoporosis/complicaciones , Vertebroplastia/instrumentación , Anciano , Anciano de 80 o más Años , Hueso Cortical/lesiones , Femenino , Fracturas por Compresión/etiología , Fracturas por Compresión/fisiopatología , Humanos , Vértebras Lumbares/lesiones , Vértebras Lumbares/fisiopatología , Masculino , Persona de Mediana Edad , Osteoporosis/cirugía , Estudios Retrospectivos , Taiwán , Vértebras Torácicas/lesiones , Vértebras Torácicas/fisiopatología , Resultado del Tratamiento , Vertebroplastia/métodos
3.
FASEB J ; 31(3): 882-892, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27864378

RESUMEN

Scleraxis (Scx) is a known regulator of tendon development, and recent work has identified the role of Scx in bone modeling. However, the role of Scx in fracture healing has not yet been explored. This study was conducted to identify the role of Scx in cortical bone development and fracture healing. Scx green fluorescent protein-labeled (ScxGFP) reporter and Scx-knockout (Scx-mutant) mice were used to assess bone morphometry and the effects of fracture healing on Scx localization and gene expression, as well as callus healing response. Botulinum toxin (BTX) was used to investigate muscle unloading effects on callus shape. Scx-mutant long bones had structural and mechanical defects. Scx gene expression was elevated and bmp4 was decreased at 24 h after fracture. ScxGFP+ cells were localized throughout the healing callus after fracture. Scx-mutant mice demonstrated disrupted callus healing and asymmetry. Asymmetry of Scx-mutant callus was not due to muscle unloading. Wild-type littermates (age matched) served as controls. This is the first study to explore the role of Scx in cortical bone mechanics and fracture healing. Deletion of Scx during development led to altered long bone properties and callus healing. This study also demonstrated that Scx may play a role in the periosteal response during fracture healing.-McKenzie, J. A., Buettmann, E., Abraham, A. C., Gardner, M. J., Silva, M. J., Killian, M. L. Loss of scleraxis in mice leads to geometric and structural changes in cortical bone, as well as asymmetry in fracture healing.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Hueso Cortical/metabolismo , Curación de Fractura , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Proteína Morfogenética Ósea 4/genética , Proteína Morfogenética Ósea 4/metabolismo , Callo Óseo/metabolismo , Hueso Cortical/lesiones , Hueso Cortical/fisiología , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología
4.
J Biomech Eng ; 140(9)2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29801171

RESUMEN

Recent studies demonstrated an association between atypical femoral fracture (AFF) and long-term bisphosphonate (BP) use for osteoporosis treatment. Due to BP treatment, bone undergoes alterations including increased microcrack density and reduced tissue compositional heterogeneity. However, the effect of these changes on the fracture response of bone is not well understood. As a result, the goal of the current study is to evaluate the individual and combined effects of microcracks and tissue compositional heterogeneity on fracture resistance of cortical bone using finite element modeling (FEM) of compact tension (CT) specimen tests with varying microcrack density, location, and clustering, and material heterogeneity in three different bone samples. The simulation results showed that an increase in microcrack density improved the fracture resistance irrespective of the local material property heterogeneity and microcrack distribution. A reduction in material property heterogeneity adversely affected the fracture resistance in models both with and without microcracks. When the combined changes in microcrack density and tissue material property heterogeneity representing BP treatment were evaluated, the models corresponding to BP-treated bone demonstrated reduced fracture resistance. The simulation results also showed that although microcrack location and clustering, and microstructure significantly influenced fracture resistance, the trends observed on the effect of microcrack density and tissue material property heterogeneity did not change. In summary, these results provide new information on the interaction of microcracks, tissue material property heterogeneity, and fracture resistance and may improve the understanding of the influence of mechanical changes due to prolonged BP use on the fracture behavior of cortical bone.


Asunto(s)
Hueso Cortical/lesiones , Fracturas Óseas , Fenómenos Mecánicos , Fenómenos Biomecánicos , Análisis de Elementos Finitos , Humanos , Modelos Biológicos
5.
Appl Opt ; 56(13): F179-F188, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28463314

RESUMEN

A bone's fracture could be produced by an excessive, repetitive, or sudden load. A regular medical practice to heal it is to fix it in two possible ways: external immobilization, using a ferule, or an internal fixation, using a prosthetic device commonly attached to the bone by means of surgical screws. The bone's volume loss due to this drilling modifies its structure either in the presence or absence of a fracture. To observe the bone's surface behavior caused by the drilling effects, a digital holographic interferometer is used to analyze the displacement surface's variations in nonfractured post-mortem porcine femoral bones. Several nondrilled post-mortem bones are compressed and compared to a set of post-mortem bones with a different number of cortical drillings. During each compression test, a series of digital interferometric holograms were recorded using a high-speed CMOS camera. The results are presented as pseudo 3D mesh displacement maps for comparisons in the physiological range of load (30 and 50 lbs) and beyond (100, 200, and 400 lbs). The high resolution of the optical phase gives a better understanding about the bone's microstructural modifications. Finally, a relationship between compression load and bone volume loss due to the drilling was observed. The results prove that digital holographic interferometry is a viable technique to study the conditions that avoid the surgical screw from loosening in medical procedures of this kind.


Asunto(s)
Tornillos Óseos/efectos adversos , Hueso Cortical/lesiones , Fémur/lesiones , Holografía/instrumentación , Imagenología Tridimensional/métodos , Animales , Hueso Cortical/química , Curación de Fractura/fisiología , Interferometría , Porcinos , Soporte de Peso
6.
Am J Orthod Dentofacial Orthop ; 152(3): 301-311, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28863910

RESUMEN

INTRODUCTION: The aim of this in-vitro study was to investigate the influence of cortical bone thickness on the amount of surface microdamage produced after insertion of orthodontic miniscrews (OM) in porcine tibia bone. METHODS: Aarhus OMs (Medicon, Tuttlingen, Germany; diameter, 1.5 mm; length, 6 mm) were inserted into 1.0 mm (group A; n = 10), 1.5 mm (group B; n = 10), and 2.0 mm (group C; n = 10) of porcine cortical bone using a torque-limiting hand screwdriver set at 18 Ncm. A sequential staining technique was used to identify microdamage under laser confocal microscopy. Virtual slices were stitched together using ImageJ software (National Institutes of Health, Bethesda, Md) to form a compressed 2-dimensional composition of the microdamage. The ImageJ software was used to quantify the total damage area, diffuse damage area, maximum crack length, maximum damage radius, and maximum diffuse damage radius. Kruskal-Wallis tests and Wilcoxon rank sum tests were used to analyze the data. RESULTS: All OMs in group A (1.0 mm) were inserted completely; however, 2 OMs from group B (1.5 mm) and all OMs in group C (2.0 mm) failed to insert completely. The entry surface of group C (2.0 mm) exhibited significantly higher amounts of total damage, diffuse damage area, maximum crack length, and maximum crack damage radius compared with groups A (1.0 mm) and B (1.5 mm). The maximum crack length observed on the entry and exit surfaces ranged from 1.03 to 3.06 mm. CONCLUSIONS: In this study, we demonstrated a higher level of microdamage after the insertion of OMs into 2.0-mm thick cortical bone compared with 1.0-mm thick cortical bone. Therefore, clinicians need to consider the thickness of the cortical bone at the insertion site, because mechanisms to reduce cortical bone thickness would likely reduce the amount of microdamage formed. A safety zone of 3.5 mm from the OM is also recommended for OMs inserted into 1.0- and 1.5-mm cortical bone thicknesses to minimize any detrimental effects after targeted remodeling.


Asunto(s)
Tornillos Óseos/efectos adversos , Hueso Cortical/lesiones , Tibia/lesiones , Animales , Remodelación Ósea , Hueso Cortical/ultraestructura , Microscopía Confocal , Porcinos , Tibia/ultraestructura
7.
Orthopade ; 46(7): 610-616, 2017 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-28364351

RESUMEN

BACKGROUND: In osteotomies with larger correction angles, the capacity for elastic deformation is frequently exceeded, resulting in plastic deformation and fracture of the opposite cortex, which may lead to subsequent loss of correction. An anteroposterior drill hole at the apex of the horizontal osteotomy (= hinge) is supposed to increase the capacity of the bony hinge for elastic deformation and ideally to prevent fractures of the opposite cortex. MATERIALS AND METHODS: A high tibial osteotomy (HTO) using standard surgical technique was performed in 20 each of Synbones, Sawbones, and human cadaver tibial specimens. In 10 specimens per group, an additional anteroposterior hinge drilling was performed at the apex of the horizontal osteotomy. All fractures of the opposite cortex were photographically and radiographically documented. All fractures were classified according to fracture types 1-3 of the Takeuchi classification. RESULTS: Regardless of the study group, all tibial bones with an additional hinge drilling achieved larger correction angles during the spreading of the wedge until a fracture of the opposite cortex occurred. The average correction angle of all specimens without the drill hole was 2.7°, which increased to 4.8° with the hinge drill (increase by 77.8%). In correction angles exceeding 5°, all specimen showed a hinge fracture regardless of the presence or absence of a hinge drill. CONCLUSIONS: The hinge-protecting effect is restricted to small correction angles, i. e., to unload cartilage repair regions in the absence of severe malalignment. For the treatment of varus gonarthrosis, there is no fracture-protecting effect from a hinge drill.


Asunto(s)
Hueso Cortical/lesiones , Complicaciones Intraoperatorias/prevención & control , Traumatismos de la Rodilla/prevención & control , Articulación de la Rodilla/cirugía , Osteotomía/métodos , Tibia/cirugía , Fracturas de la Tibia/prevención & control , Hueso Cortical/diagnóstico por imagen , Humanos , Complicaciones Intraoperatorias/diagnóstico por imagen , Traumatismos de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Factores de Riesgo , Tibia/diagnóstico por imagen , Tibia/lesiones , Fracturas de la Tibia/diagnóstico por imagen
8.
Arch Orthop Trauma Surg ; 136(8): 1115-20, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27379975

RESUMEN

PURPOSE: Exclusion or detection of non-displaced radial head fractures can be difficult in radiographs, because they might lack conclusive radiographic signs, such as fracture lines or distracted articular fragments. Based on the typical injury mechanism of a radial head fracture, causing the head to hit the capitulum and leading to a depression of the anterolateral border of the radial head, we hypothesized that even slight cortical irregularities in the transition zone of the radial neck and head result from that depression and may be a reliable radiographic sign of an underlying radial head fracture. Secondarily, we tested the null hypothesis that the lack of cortical irregularities is sufficient to exclude a fracture of the radial head. METHODS: 84 patients with sets of anteroposterior and lateral radiographs of the elbow were identified from the database of a level 1 trauma center and divided into 2 groups. Group A was formed out of 42 patients with non-displaced radial head fractures, group B out of 42 patients without a history of previous elbow trauma, whose medical history also contained radiographic images. After the radial head was blackened, the transition zone of the radial neck and head was assessed by two attending orthopedic surgeons for presence of a cortical irregularity. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cortical irregularity were calculated for the assessment of radial head fractures. The kappa measure of agreement was utilized to evaluate interrater agreement. RESULTS: The specificity was 87.80 and 97.56 %, respectively, its sensitivity 86.04 and 75.61 %. A high NPV (85.71 %; 80.00 %) and PPV (96.88 %; 88.10 %.) were observed. The interrater agreement for the proposed diagnostic method was high, with a Cohen kappa score of 0.737 (p < 0.001). CONCLUSIONS: A cortical irregularity in the transition zone of the radial neck and head seems to be a reliable radiographic sign of an underlying radial head fracture. The absence of the cortical irregularity can be used to correctly identify a non-fractured radial head.


Asunto(s)
Hueso Cortical/diagnóstico por imagen , Fracturas del Radio/diagnóstico por imagen , Radio (Anatomía)/diagnóstico por imagen , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Hueso Cortical/lesiones , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Adulto Joven
9.
PLoS One ; 16(7): e0253862, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34197561

RESUMEN

A finite element analysis was performed to evaluate the stresses around nails and cortical bones in subtrochanteric (ST) fracture models fixed using short cephalomedullary nails (CMNs). A total 96 finite element models (FEMs) were simulated on a transverse ST fracture at eight levels with three different fracture gaps and two different distal locking screw configurations in both normal and osteoporotic bone. All FEMs were fixed using CMNs 200 mm in length. Two distal locking screws showed a wider safe range than 1 distal screw in both normal and osteoporotic bone at fracture gaps ≤ 3 mm. In normal bone FEMs fixed even with two distal locking screws, peak von Mises stresses (PVMSs) in cortical bone and nail constructs reached or exceeded 90% of the yield strength at fracture levels 50 mm and 0 and 50 mm, respectively, at all fracture gaps. In osteoporotic bone FEMs, PVMSs in cortical bone and nail constructs reached or exceeded 90% of the yield strength at fracture levels 50 mm and 0 and 50 mm, respectively, at a 1-mm fracture gap. However, at fracture gaps ≥ 2 mm, PVMSs in cortical bone reached or exceeded 90% of the yield strength at fracture levels ≥ 35 mm. PVMSs in nail showed the same results as 1-mm fracture gaps. PVMSs increased and safe range reduced, as the fracture gap increased. Short CMNs (200 mm in length) with two distal screws may be considered suitable for the fixation of ST transverse fractures at fracture levels 10 to 40 mm below the lesser trochanter in normal bone and 10 to 30 mm in osteoporotic bone, respectively, under the assumptions of anatomical reduction at fracture gap ≤ 3 mm. However, the fracture gap should be shortened to the minimum to reduce the risk of refracture and fixation failure, especially in osteoporotic fractures.


Asunto(s)
Clavos Ortopédicos , Hueso Cortical/lesiones , Fijación Intramedular de Fracturas/instrumentación , Fracturas de Cadera/cirugía , Osteoporosis/cirugía , Fenómenos Biomecánicos , Tornillos Óseos , Hueso Cortical/patología , Hueso Cortical/cirugía , Análisis de Elementos Finitos , Fracturas de Cadera/etiología , Fracturas de Cadera/patología , Humanos , Osteoporosis/complicaciones , Osteoporosis/patología
10.
Forensic Sci Int ; 319: 110661, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33360603

RESUMEN

Cut marks provide essential knowledge to interpret which and how tools were used, both in archaeological and forensic context. Lots of studies focused on experimentally produced cut marks on animal models to develop methods for stabbing incidents. However, animal models are criticized to be morphologically different in comparison to human bones. This study analyzed the bone composition and experimentally obtained cut marks done on ribs from humans, pigs and goats. Methods included a qualitative description of differences between the species and a quantitative analysis of the cut mark proportions in histological thin sections and micro CT scans. The results indicated that especially the cortical bone of non-human ribs was different in comparison to human bone tissue as they were more robust and usually juvenile. Plexiform bone dominates and remodeled lamellar bone is rarely visible. The knife impact tends to create debris inside the cut mark and stress fractures along lamellae and cement lines perpendicular to the cut mark. Moreover, entheses of the intercostal muscles are always affected by the incision. Pig ribs were shown to be better suited as a model for sharp force trauma than goat ribs in comparison to humans. Though, plexiform bone and non-remodeled bone made it not quite ideal. We suggested to use bone material from animals used for breeding instead of meat production as they are slaughtered at higher ages.


Asunto(s)
Fracturas de las Costillas/patología , Costillas/lesiones , Costillas/patología , Heridas Punzantes/patología , Anciano , Animales , Hueso Esponjoso/lesiones , Hueso Esponjoso/patología , Hueso Cortical/lesiones , Hueso Cortical/patología , Patologia Forense , Fracturas por Estrés/diagnóstico por imagen , Fracturas por Estrés/patología , Cabras , Humanos , Masculino , Modelos Animales , Fracturas de las Costillas/diagnóstico por imagen , Costillas/diagnóstico por imagen , Porcinos , Heridas Punzantes/diagnóstico por imagen , Microtomografía por Rayos X
11.
Medicine (Baltimore) ; 100(2): e24099, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33466177

RESUMEN

BACKGROUND: To explore the ideal trajectory of lumbar cortical bone trajectory screws and provide the optimal placement scheme in clinical applications. METHODS: Lumbar computed tomography (CT) data of 40 patients in our hospital were selected, and the cortical vertebral bone contour model was reconstructed in three dimensions (3D). Depending on the different regions of the screw through the entrance and exit of the pedicle, 9 trajectories were obtained through combinational design: T-Aa, T-Ab, T-Ac, T-Ba, T-Bb, T-Bc, T-Ca, T-Cb, and T-Cc. Cortical bone trajectory (CBT) screws with appropriate diameters were selected to simulate screw placement and measure the parameters corresponding to each trajectory (screw path diameter, screw trajectory length, cephalad angle, and lateral angle), and then determine the optimal screw according to the screw parameters and screw safety. Then, 23 patients in our hospital were selected, and the navigation template was designed based on the ideal trajectory before operation, CBT screws were placed during the operation to further verify the safety and feasibility of the ideal trajectory. RESULTS: T-Bc and T-Bb are the ideal screw trajectories for L1-L2 and L3-L5, respectively. The screw placement point is located at the intersection of the inner 1/3 vertical line of the superior facet joint and the bottom 1/3 horizontal line of the outer crest of the vertebral lamina (i.e., 2-4 mm inward at the bottom 1/3 of the outer crest of the vertebral lamina). CBT screws were successfully placed based on the ideal screw trajectory in clinical practice. During the operation or the follow-up period, there were no adverse events. CONCLUSION: CBT screw placement based on the ideal screw trajectory is a safe and reliable method for achieving effective fixation and satisfactory postoperative effects.


Asunto(s)
Hueso Cortical/lesiones , Fijación de Fractura/instrumentación , Vértebras Lumbares/lesiones , Tornillos Pediculares , Fracturas de la Columna Vertebral/cirugía , Simulación por Computador , Hueso Cortical/diagnóstico por imagen , Hueso Cortical/cirugía , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Modelos Anatómicos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Articulación Cigapofisaria/diagnóstico por imagen , Articulación Cigapofisaria/cirugía
12.
Proc Inst Mech Eng H ; 234(3): 247-254, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31648627

RESUMEN

Cortical bone fracture mechanisms are well studied under quasi-static loading. The influence of strain rate on crack propagation mechanisms needs to be better understood, however. We have previously shown that several aspects of the bone micro-structure are involved in crack propagation, such as the complete porosity network, including the Haversian system and the lacunar network, as well as biochemical aspects, such as the maturity of collagen cross-links. The aim of this study is to investigate the influence of strain rate on the toughness of human cortical bone with respect to its microstructure and organic non-collagenous composition. Two strain rates will be considered: quasi-static loading (10-4 s-1), a standard condition, and a higher loading rate (10-1 s-1), representative of a fall. Cortical bone samples were extracted from eight female donors (age 50-91 years). Three-point bending tests were performed until failure. Synchrotron radiation micro-computed tomography imaging was performed to assess bone microstructure including the Haversian system and the lacunar system. Collagen enzymatic cross-link maturation was measured using a high performance liquid chromatography column. Results showed that that under quasi-static loading, the elastic contribution of the fracture process is correlated to both the collagen cross-links maturation and the microstructure, while the plastic contribution is correlated only to the porosity network. Under fall-like loading, bone organization appears to be less linked to crack propagation.


Asunto(s)
Hueso Cortical/fisiología , Estrés Mecánico , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Hueso Cortical/citología , Hueso Cortical/diagnóstico por imagen , Hueso Cortical/lesiones , Femenino , Humanos , Persona de Mediana Edad , Microtomografía por Rayos X
13.
Sci Rep ; 10(1): 21804, 2020 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-33311522

RESUMEN

Previous studies examining the role of the histone deacetylase Hdac3 within myeloid cells demonstrated that Hdac3 promotes M2 activation and tissue healing in inflammatory conditions. Since myeloid lineage cells are required for proper bone formation and regeneration, in this study we examined the functions of Hdac3 during bone healing. Conditional deletion of Hdac3 within myeloid progenitors accelerates healing of cortical bone defects. Moreover, reduced osteoclast numbers within the defect site are correlated with Hdac3 suppression. Ex vivo osteoclastogenesis assays further demonstrate that Hdac3 deficiency limits osteoclastogenesis, the number of nuclei per cell and bone resorption, suggesting a defect in cell fusion. High throughput RNA sequencing identified the transmembrane protein Pmepa1 as a differentially expressed gene within osteoclast progenitor cells. Knockdown of Pmepa1 partially restores defects in osteoclastogenesis induced by Hdac3 deficiency. These results show that Hdac3 is required for optimal bone healing and osteoclast fusion, potentially via its regulation of Pmepa1 expression.


Asunto(s)
Regeneración Ósea , Hueso Cortical/metabolismo , Eliminación de Gen , Histona Desacetilasas/deficiencia , Proteínas de la Membrana/metabolismo , Células Progenitoras Mieloides/metabolismo , Osteoclastos/metabolismo , Animales , Fusión Celular , Hueso Cortical/lesiones , Hueso Cortical/patología , Femenino , Histona Desacetilasas/metabolismo , Proteínas de la Membrana/genética , Ratones , Ratones Noqueados , Células Progenitoras Mieloides/patología , Osteoclastos/patología
14.
J Biomech ; 100: 109596, 2020 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-31898977

RESUMEN

This work investigates how changes in cortical bone microstructure alter the risk of fragility fractures. The secondary osteons of non-osteoporotic (by DXA) women with fragility fractures have reduced lamellar width and greater areas of birefringent brightness in transverse sections, a pathological condition. We used hierarchical finite element (FE) models of the proximal femur of two women aged 67 and 88 (younger and older) during one-legged stance. At specific locations of the anterior-inferior neck (ROI), we analyzed micro-models containing osteons comprised of alternating birefringent extinct and bright lamellae. The plane of lamellar isotropy (XY) was transverse to the osteon longitudinal axis (Z) which was parallel to the femoral neck axis. To evaluate changes in fracture risk with changes in microstructure, we investigated principal and von Mises stresses, and planar stress measures that accounted for transverse isotropy. For both younger and older femurs, 48% to 100% of stress measures were larger in models with healthy architecture than in models with pathological architecture, while controlling for type of lamella and osteon. These findings suggest that bone adaptation reduces stress at most pathological lamellar sites. However, in the bright lamellae of the younger femur, the pathological tensile, compressive and distortional stresses in the transverse plane and distortional stress in the longitudinal planes were larger than the non-negligible corresponding stresses in 6 of the 28 osteon models with healthy architecture, in 5 of the 7 locations. Therefore, a minority of sites with pathological architecture present greater stress, and therefore, greater fracture risk.


Asunto(s)
Hueso Cortical/citología , Hueso Cortical/lesiones , Fracturas Óseas/patología , Estrés Mecánico , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Hueso Cortical/patología , Hueso Cortical/fisiopatología , Femenino , Fémur/lesiones , Fémur/patología , Fémur/fisiopatología , Fracturas Óseas/fisiopatología , Humanos , Persona de Mediana Edad
15.
Mater Sci Eng C Mater Biol Appl ; 113: 110981, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32487395

RESUMEN

Bone tissue engineering aims to alleviate the shortage of available autograft material and the biological/mechanical incompatibility of allografts through fabrication of bioactive synthetic bone graft substitutes. However, these substitute grafting materials have insufficient biological potency that limits their clinical efficacy in regenerating large defects. Extracellular matrix, a natural tissue scaffold laden with biochemical and structural cues regulating cell adhesion and tissue morphogenesis, may be a versatile supplement that can extend its biological functionality to synthetic grafts. Embedding decellularized extracellular matrix (dECM) into synthetic polymers offers a promising strategy to enhance cellular response to synthetic materials, mitigate physical and mechanical limitations of dECMs, and improve clinical utility of synthetic bone grafts. Enriched with dECM biochemical cues, synthetic polymers can be readily fabricated into complex biocomposite grafts that mimic bone structure and stimulate endogenous cells to regenerate bone. In this study, cell-derived dECMs from osteoblast and endothelial cells were incorporated into polycaprolactone (PCL) solutions for electrospinning dual-layer nanofibrous scaffolds with osteogenic and vascular cues. The study examined the bioactivity of dECM scaffolds in osteoblast cultures for cell number, mineral deposits, and osteogenic markers, as well as regeneration of cortical bone defect in a rat femur. Scaffolds with osteoblast dECM had a significantly robust osteoblast proliferation, Alizarin Red staining/concentration, and osteopontin-positive extracellular deposits. Implanted scaffolds increased bone growth in femoral defects, and constructs with both osteogenic and vascular cues significantly improved cortical width. These findings demonstrate the potential to fabricate tailored biomimetic grafts with dECM cues and fibrous architecture for bone applications.


Asunto(s)
Regeneración Ósea , Matriz Extracelular/química , Nanofibras/química , Poliésteres/química , Andamios del Tejido/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Regeneración Ósea/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Hueso Cortical/lesiones , Hueso Cortical/patología , Matriz Extracelular/metabolismo , Masculino , Osteoblastos/citología , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteopontina/metabolismo , Porosidad , Ratas , Ratas Sprague-Dawley , Resistencia a la Tracción , Ingeniería de Tejidos
16.
J Mech Behav Biomed Mater ; 90: 556-565, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30472565

RESUMEN

Reliable tools for fracture risk assessment are necessary to handle the challenge with an aging population and the increasing occurrence of bone fractures. As it is currently difficult to measure local damage parameters experimentally, computational models could be used to provide insight into how cortical bone microstructure and material properties contribute to the fracture resistance. In this study, a model for crack propagation in 2D at the microscale in cortical bone was developed using the extended finite element method (XFEM). By combining the maximum principal strain criterion with an additional interface damage formulation in the cement line, the model could capture crack deflections at the osteon boundaries as observed in experiments. The model was used to analyze how the Haversian canal and the interface strength of the cement line affected the crack trajectory in models depicting osteons with three different orientations in 2D. Weak cement line interfaces were found to reorient the propagating cracks while models with strong interfaces predicted crack trajectories that penetrated the cement line and propagated through the osteons. The presented model is a promising tool that could be used to analyze how local, age-related material changes influence the crack trajectory and fracture resistance in cortical bone.


Asunto(s)
Hueso Cortical/lesiones , Análisis de Elementos Finitos , Fracturas Óseas , Fenómenos Mecánicos , Modelos Biológicos , Fenómenos Biomecánicos , Osteón/lesiones , Estrés Mecánico
17.
Proc Inst Mech Eng H ; 233(8): 823-838, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31169079

RESUMEN

Stress intensity factor and energy release rate are important parameters to understand the fracture behaviour of bone. The objective of this study is to predict stress intensity factor and energy release rate using finite element method, element-free Galerkin method, and extended finite element method and compare these results with the experimentally determined values. For experimental purpose, 20 longitudinally and transversely fractured single-edge notched bend specimens were prepared and tested according to ASTM standard. All specimens were tested using the universal testing machine. For numerical simulations (finite element method, element-free Galerkin method, and extended finite element method), two-dimensional model of cortical bone was developed by assuming plane strain condition. Material properties of the cortical bone were considered as anisotropic and homogeneous. The values obtained through finite element method, element-free Galerkin method, and extended finite element method are well corroborated to experimentally determined values and earlier published data. However, element-free Galerkin method and extended finite element method predict more accurate results as compared to finite element method. In the case of the transversely fractured specimen, the values of stress intensity factor and energy release rate were found to be higher as compared to the longitudinally fractured specimen, which shows consistency with earlier published data. This study also indicates element-free Galerkin method and extended finite element method predicted stress intensity factor and energy release rate results are more close to experimental results as compared to finite element method, and therefore, these methods can be used in the different field of biomechanics, particularly to predict bone fracture.


Asunto(s)
Hueso Cortical/fisiología , Análisis de Elementos Finitos , Modelos Biológicos , Estrés Mecánico , Anisotropía , Fenómenos Biomecánicos , Hueso Cortical/lesiones , Hueso Cortical/fisiopatología , Fracturas Óseas/fisiopatología , Ensayo de Materiales
18.
J Orthop Surg Res ; 14(1): 1, 2019 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-30606215

RESUMEN

BACKGROUND: This study aimed to explore the effect of retaining inferomedial cortical bone contact and fixation with calcar screws on the dynamic and static mechanical stability of proximal humerus fractures treated with a locking plate. METHODS: Twelve Synbone prosthetic humeri (SYNBONE-AG, Switzerland) were used for a wedge osteotomy model at the proximal humerus, in four groups. In the cortex contact + screw fixation group and cortex contact group, the inferomedial cortical bone contact was retained. In the screw fixation group and control group, the inferomedial cortical bone contact was not retained. Calcar screw fixation was implemented only in the screw fixation groups. The dynamic and static mechanical stability of the models were tested with dynamic fatigue mechanics testing, quasi-static axial compression, three-point bending, and torsion testing. RESULTS: The cortex contact + screw fixation group showed the longest fatigue life and the best stability. There was 35% difference in fatigue life between the cortex contact + screw fixation group and the cortex contact group, 43%between the cortex contact + screw fixation group and screw fixation group, and 63% between the cortex contact + screw fixation group and screw fixation group (P < 0.01). The cortex contact + screw fixation group showed the best axial compressive stiffness, bending stiffness, and torsion stiffness; these were successively decreased in the other three groups (P < 0.01). CONCLUSION: Retaining inferomedial cortical bone contact and fixation with two calcar screws maintained fracture stability with the highest strength and minimum deformation. Of the two methods, restoration of the inferomedial cortical bone support showed better dynamic and static biomechanical properties than placement of calcar screws alone.


Asunto(s)
Tornillos Óseos/normas , Hueso Cortical/cirugía , Ensayo de Materiales/normas , Fracturas del Hombro/cirugía , Fuerza Compresiva/fisiología , Hueso Cortical/lesiones , Hueso Cortical/patología , Humanos , Ensayo de Materiales/métodos , Distribución Aleatoria , Fracturas del Hombro/patología
19.
Acta Biomater ; 90: 278-286, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30926579

RESUMEN

The initiation and propagation of physiological cracks in porcine cortical and cancellous bone under high rate loading were visualized using high-speed synchrotron X-ray phase-contrast imaging (PCI) to characterize their fracture behaviors under dynamic loading conditions. A modified Kolsky compression bar was used to apply dynamic three-point flexural loadings on notched specimens and images of the fracture processes were recorded using a synchronized high-speed synchrotron X-ray imaging set-up. Three-dimensional synchrotron X-ray tomography was conducted to examine the initial microstructure of the bone before high-rate experiments. The experimental results showed that the locations of fracture initiations were not significantly different between the two types of bone. However, the crack velocities in cortical bone were higher than in cancellous bone. Crack deflections at osteonal cement lines, a prime toughening mechanism in bone at low rates, were observed in the cortical bone under dynamic loading in this study. Fracture toughening mechanisms, such as uncracked ligament bridging and bridging in crack wake were also observed for the two types of bone. The results also revealed that the fracture toughness of cortical bone was higher than cancellous bone. The crack was deflected to some extent at osteon cement line in cortical bone instead of comparatively penetrating straight through the microstructures in cancellous bone. STATEMENT OF SIGNIFICANCE: Fracture toughness is with great importance to study for crack risk prediction in bone. For those cracks in bone, most of them are associated with impact events, such as sport accidents. Consequently, we visualized, in real-time, the entire processes of dynamic fractures in notched cortical bone and cancellous bone specimens using synchrotron X-ray phase contrast imaging. The onset location of crack initiation was found independent on the bone type. We also found that, although the extent was diminished, crack deflections at osteon cement lines, a major toughening mechanism in transversely orientated cortical bone at quasi-static rate, were still played a role in resisting cracking in dynamically loaded specimen. These finding help researchers to understand the dynamic fracture behaviors in bone.


Asunto(s)
Hueso Esponjoso , Hueso Cortical , Fracturas Óseas , Modelos Biológicos , Tomografía Computarizada por Rayos X , Animales , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/lesiones , Hueso Esponjoso/fisiopatología , Hueso Cortical/diagnóstico por imagen , Hueso Cortical/lesiones , Hueso Cortical/fisiopatología , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/fisiopatología , Porcinos
20.
Ann Biomed Eng ; 47(12): 2384-2401, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31342335

RESUMEN

The ability to rapidly detect localised fractures of cortical and/or trabecular bone sustained by the vertebral body would enhance the analysis of vertebral fracture initiation and propagation during dynamic loading. In this study, high rate axial compression tests were performed on twenty sets of three-vertebra lumbar spine specimens. Acoustic Emission (AE) sensor measurements of sound wave pressure were used to classify isolated trabecular fractures and severe compressive fractures of vertebral body cortical and trabecular bone. Fracture detection using standard AE parameters was compared to that of traditional mechanical parameters obtained from load cell and displacement readings. Results indicated that the AE parameters achieved slightly enhanced classification of isolated trabecular fractures, whereas the mechanical parameters better identified combined fractures of cortical and trabecular bone. These findings demonstrate that AE may be used to promptly and accurately identify localised fractures of trabecular bone, whereas more extensive fractures of the vertebral body are best identified by load cell readings due to the considerable loss in compressive resistance. The discrimination thresholds corresponding to the AE parameters were based on calibrated measurements of AE wave pressure and may ultimately be used to examine the onset and progression of vertebral fracture in other loading scenarios.


Asunto(s)
Hueso Esponjoso/lesiones , Hueso Cortical/lesiones , Fracturas Óseas/diagnóstico , Vértebras Lumbares/lesiones , Acústica , Anciano , Fenómenos Biomecánicos , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/fisiopatología , Hueso Cortical/diagnóstico por imagen , Hueso Cortical/fisiopatología , Fracturas Óseas/fisiopatología , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/fisiopatología , Masculino , Persona de Mediana Edad , Estrés Mecánico , Tomografía Computarizada por Rayos X
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