RESUMEN
Magnesium (Mg)-based implants have become of interest to both academia and the medical industry. The attraction largely is due to Mg's biodegradability and ability to enhance bone healing and formation. However, the underlying mechanism of how Mg regulates osteogenesis is still unclear. Based on our previous in vivo and molecular signaling work demonstrating the osteogenic effect of Mg, the current study aims to extend this work at the molecular level especially that we also observed and quantified mineral deposits in the bone marrow space in a rabbit ulna fracture model with Mg plates and screws. Histological analysis and quantitative results of micro-CT showed mineralized deposition and a significant increase in bone volume at 8â¯weeks and 16â¯weeks post-operative. These in vivo results led us to focus on studying the effect of Mg2+ on human bone marrow stromal cells (hBMSCs). The data presented in this manuscript demonstrate the activation of the canonical Wnt signaling pathway in hBMSCs when treated with 10â¯mMâ¯Mg2+. With additional Mg2+ present, the protein expression of active ß-catenin was significantly increased to a level similar to that of the positive control. Immunocytochemistry and the increased expression of LEF1 and Dkk1, downstream target genes that are controlled directly by active ß-catenin, demonstrated the protein translocation and the activation of transcription. Taken together, these data suggest that Mg2+ induces an osteogenic effect in the bone marrow space by activating the canonical Wnt signaling pathway, which in turn causes BMSCs to differentiate toward the osteoblast lineage. STATEMENT OF SIGNIFICANCE: Magnesium (Mg)-based alloys are being studied to be used in the field of implantable medical devices due to its natural biodegradability and the potential ability to promote bone regeneration. Despite many in vivo studies that demonstrated an increased new bone growth by implanting Mg-based devices, the underlying mechanism of this effect is still unclear. In order to safely use Mg-based implants on human and better control the osteogenic effect, it is necessary to understand the corresponding cellular response in the targeted area. The present study provides the rationale to study Mg ions on bone marrow stromal cells and shows the activation of canonical Wnt signaling pathway that promotes osteogenesis by in vivo and in vitro approaches.
Asunto(s)
Regeneración Ósea/efectos de los fármacos , Magnesio/farmacología , Vía de Señalización Wnt/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Animales , Calcificación Fisiológica/efectos de los fármacos , Iones , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Conejos , Transcripción Genética/efectos de los fármacos , Vía de Señalización Wnt/genética , Microtomografía por Rayos X , beta Catenina/metabolismoRESUMEN
PURPOSE: To compare the fluid delivery performance of 2 different technologies for administration of iodinated contrast media in computed tomography (CT). METHODS: The maximum achievable flow rate and the steady-state flow rate variance of a piston-based contrast media injector system (Stellant MP, MEDRAD) was compared with peristaltic pump-based injector systems (CT motion, Ulrich Medical; CT Exprès, Bracco). The contrast media iopromide (Ultravist) and iopamidol (Isovue) were used at 2 concentrations each (300 and 370 mg I/mL) and 3 catheter sizes (18, 20, and 22 G) to test the injector performance. RESULTS: Average maximum achievable flow rates for room temperature iopromide (370 mg I/mL) using a 20 G catheter were 7.6, 7.1, and 4.8 mL per second for the Stellant MP injector, CT motion injector, and CT Exprès injector, respectively. The Stellant MP injector achieved significantly higher flow rates compared to the CT Exprès injector for all catheter sizes tested (P<.001). Higher flow rates also were observed for the Stellant MP injector compared to the CT motion injector, with 20 G and 22 G catheters (P<.001). The Stellant MP injector featured a constant steady-state flow rate (variance<0.04 mL/s), whereas the other systems injected in a pulsatile fashion, with significantly greater variance (P<.001). DISCUSSION: To the authors' knowledge, this is the first reported laboratory study providing preliminary evidence of differences between the fluid delivery performance of CT injection systems. Additional investigations using a dedicated flow phantom simulating human physiological flow parameters should be conducted, and depending on the results, a clinical study could assess the effect on image quality. CONCLUSION: The piston-based injector demonstrated higher maximum achievable flow rates and more consistent steady-state flow when compared to peristaltic pump-based injectors.
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Cateterismo/instrumentación , Medios de Contraste/administración & dosificación , Inyecciones Intravenosas/instrumentación , Yohexol/análogos & derivados , Yopamidol/administración & dosificación , Diseño de Equipo , Humanos , Yohexol/administración & dosificación , Tomografía Computarizada por Rayos XRESUMEN
Magnesium (Mg) alloys have many unique qualities which make them ideal candidates for bone fixation devices, including biocompatibility and degradation in vivo. Despite a rise in Mg alloy production and research, there remains no standardized system to assess their degradation or biological effect on human stem cells in vivo. In this study, we developed a novel in vivo model to assess Mg alloys for craniofacial and orthopedic applications. Our model consists of a collagen sponge seeded with human bone marrow stromal cells (hBMSCs) around a central Mg alloy rod. These scaffolds were implanted subcutaneously in mice and analyzed after eight weeks. Alloy degradation and biological effect were determined by microcomputed tomography (microCT), histological staining, and immunohistochemistry (IHC). MicroCT showed greater volume loss for pure Mg compared to AZ31 after eight weeks in vivo. Histological analysis showed that hBMSCs were retained around the Mg implants after 8 weeks. Furthermore, immunohistochemistry showed the expression of dentin matrix protein 1 and osteopontin around both pure Mg and AZ31 with implanted hBMSCs. In addition, histological sections showed a thin mineral layer around all degrading alloys at the alloy-tissue interface. In conclusion, our data show that degrading pure Mg and AZ31 implants are cytocompatible and do not inhibit the osteogenic property of hBMSCs in vivo. These results demonstrate that this model can be used to efficiently assess the biological effect of corroding Mg alloys in vivo. Importantly, this model may be modified to accommodate additional cell types and clinical applications. STATEMENT OF SIGNIFICANCE: Magnesium (Mg) alloys have been investigated as ideal candidates for bone fixation devices due to high biocompatibility and degradation in vivo, and there is a growing need of establishing an efficient in vivo material screening system. In this study, we assessed degradation rate and biological effect of Mg alloys by transplanting Mg alloy rod with human bone marrow stromal cells seeded on collagen sponge subcutaneously in mice. After 8 weeks, samples were analyzed by microcomputed tomography and histological staining. Our data show that degrading Mg alloys are cytocompatible and do not inhibit the osteogenic property of hBMSCs in vivo. These results demonstrate that this model can be used to efficiently assess the biological effect of corroding Mg alloys in vivo.
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Aleaciones , Magnesio/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Modelos Biológicos , Células Cultivadas , HumanosRESUMEN
Each year, millions of Americans suffer bone fractures, often requiring internal fixation. Current devices, like plates and screws, are made with permanent metals or resorbable polymers. Permanent metals provide strength and biocompatibility, but cause long-term complications and may require removal. Resorbable polymers reduce long-term complications, but are unsuitable for many load-bearing applications. To mitigate complications, degradable magnesium (Mg) alloys are being developed for craniofacial and orthopedic applications. Their combination of strength and degradation make them ideal for bone fixation. Previously, we conducted a pilot study comparing Mg and titanium devices with a rabbit ulna fracture model. We observed Mg device degradation, with uninhibited healing. Interestingly, we observed bone formation around degrading Mg, but not titanium, devices. These results highlighted the potential for these fixation devices. To better assess their efficacy, we conducted a more thorough study assessing 99.9% Mg devices in a similar rabbit ulna fracture model. Device degradation, fracture healing, and bone formation were evaluated using microcomputed tomography, histology and biomechanical tests. We observed device degradation throughout, and calculated a corrosion rate of 0.40±0.04mm/year after 8 weeks. In addition, we observed fracture healing by 8 weeks, and maturation after 16 weeks. In accordance with our pilot study, we observed bone formation surrounding Mg devices, with complete overgrowth by 16 weeks. Bend tests revealed no difference in flexural load of healed ulnae with Mg devices compared to intact ulnae. These data suggest that Mg devices provide stabilization to facilitate healing, while degrading and stimulating new bone formation.
Asunto(s)
Placas Óseas , Tornillos Óseos , Curación de Fractura/efectos de los fármacos , Magnesio/farmacología , Fracturas del Cúbito/patología , Animales , Desarrollo Óseo/efectos de los fármacos , Ensayo de Materiales , Conejos , Cúbito/diagnóstico por imagen , Cúbito/efectos de los fármacos , Cúbito/patología , Fracturas del Cúbito/diagnóstico por imagen , Microtomografía por Rayos XRESUMEN
PURPOSE: Internal bone fixation devices made with permanent metals are associated with numerous long-term complications and may require removal. We hypothesized that fixation devices made with degradable magnesium alloys could provide an ideal combination of strength and degradation, facilitating fracture fixation and healing while eliminating the need for implant removal surgery. MATERIALS AND METHODS: Fixation plates and screws were machined from 99.9% pure magnesium and compared with titanium devices in a rabbit ulnar fracture model. Magnesium device degradation and the effect on fracture healing and bone formation were assessed after 4 weeks. Fracture healing with magnesium device fixation was compared with that of titanium devices using qualitative histologic analysis and quantitative histomorphometry. RESULTS: Micro-computed tomography showed device degradation after 4 weeks in vivo. In addition, 2-dimensional micro-computed tomography slices and histologic staining showed that magnesium degradation did not inhibit fracture healing or bone formation. Histomorphology showed no difference in bone-bridging fractures fixed with magnesium and titanium devices. Interestingly, abundant new bone was formed around magnesium devices, suggesting a connection between magnesium degradation and bone formation. CONCLUSION: Our results show potential for magnesium fixation devices in a loaded fracture environment. Furthermore, these results suggest that magnesium fixation devices may enhance fracture healing by encouraging localized new bone formation.
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Placas Óseas , Tornillos Óseos , Curación de Fractura , Fijadores Internos , Animales , Osteogénesis , Conejos , Microtomografía por Rayos XRESUMEN
We have developed a prototype of a real-time, interactive projective overlay (IPO) system that creates augmented reality display of a medical procedure directly on the surface of a full-body mannequin human simulator. These images approximate the appearance of both anatomic structures and instrument activity occurring within the body. The key innovation of the current work is sensing the position and motion of an actual device (such as an endotracheal tube) inserted into the mannequin and using the sensed position to control projected video images portraying the internal appearance of the same devices and relevant anatomic structures. The images are projected in correct registration onto the surface of the simulated body. As an initial practical prototype to test this technique we have developed a system permitting real-time visualization of the intra-airway position of an endotracheal tube during simulated intubation training.
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Instrucción por Computador/métodos , Imagenología Tridimensional/métodos , Intubación Intratraqueal/métodos , Maniquíes , Modelos Biológicos , Cirugía Asistida por Computador/métodos , Interfaz Usuario-Computador , Simulación por Computador , Sistemas de Computación , Humanos , Enseñanza/métodosRESUMEN
A fall detection system and algorithm, incorporated into a custom designed garment has been developed. The developed fall detection system uses a tri-axial accelerometer, microcontroller, battery and Bluetooth module. This sensor is attached to a custom designed vest, designed to be worn by the elderly person under clothing. The fall detection algorithm was developed and incorporates both impact and posture detection capability. The vest and fall algorithm was tested on young healthy subjects performing normal activities of daily living (ADL) and falls onto crash mats, while wearing the best and sensor. Results show that falls can de distinguished from normal activities with a sensitivity >90% and a specificity of >99%, from a total data set of 264 falls and 165 normal ADL. By incorporating the fall-detection sensor into a custom designed garment it is anticipated that greater compliance when wearing a fall-detection system can be achieved and will help reduce the incidence of the long-lie, when falls occur in the elderly population. However further long-term testing using elderly subjects is required to validate the systems performance.
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Accidentes por Caídas/prevención & control , Monitoreo Ambulatorio/métodos , Movimiento/fisiología , Procesamiento de Señales Asistido por Computador , Aceleración , Actividades Cotidianas , Adulto , Anciano , Algoritmos , Fenómenos Biomecánicos , Vestuario , Diseño de Equipo , Humanos , Masculino , Ensayo de MaterialesRESUMEN
A fall detection system and algorithm, incorporated into a custom designed garment has been developed. The developed fall detection system uses a tri-axial accelerometer to detect impacts and monitor posture. This sensor is attached to a custom designed vest, designed to be worn by the elderly person under clothing. The fall detection algorithm was developed and incorporates both impact and posture detection capability. The vest and fall algorithm was tested by two teams of 5 elderly subjects who wore the sensor system in turn for 2 week each and were monitored for 8 hours a day. The system previously achieved sensitivity of >90% and a specificity of >99%, using young healthy subjects performing falls and normal activities of daily living (ADL). In this study, over 833 hours of monitoring was performed over the course of the four weeks from the elderly subjects, during normal daily activity. In this time no actual falls were recorded, however the system registered a total of the 42 fall-alerts however only 9 were received at the care taker site. A fall detection system incorporated into a custom designed garment has been developed which will help reduce the incidence of the long-lie, when falls occur in the elderly population. However further development is required to reduce the number of false-positives and improve the transmission of messages.