RESUMEN
PURPOSE: This study compared the degradation profile, safety, and efficacy of bioresorbable magnesium alloy and polylactide-co-glycolide (PLGA) polymer osteosynthesis systems for the treatment of fractures in a load-sharing maxillofacial environment using a new mini-swine fracture fixation model. MATERIALS AND METHODS: Two types of clinically relevant situations were evaluated in 5 Yucatan miniature pigs. Defined porcine midface osteotomies of the supraorbital rim and zygoma were created and fixed with either a coated magnesium (test animals) or PLGA plate and screw osteosynthesis system (control animals). After surgery, the mini-pigs were able to recover for either 1 or 9 months with continuous in vivo post-implantation monitoring. Standardized computed tomography (CT) imaging was taken immediately postoperatively and at termination for all animals. The 9-month cohort also underwent CT at 2, 4, and 6 months after surgery. At necropsy, osteotomy sites and bone-implant units were harvested, and healing was evaluated by micro-CT, histopathology, and histomorphometry. RESULTS: After clinical and radiologic follow-up examination, all fracture sites healed well for both the magnesium and polymer groups regardless of time point. Complete bone union and gradually disappearing osteotomy lines were observed across all implantation sites, with no major consistency change in periprosthetic soft tissue or in soft tissue calcification. Macroscopic and microscopic examination showed no negative influence of gas formation observed with magnesium during the healing process. Histopathologic analysis showed similar fracture healing outcomes for both plating systems with good biocompatibility as evidenced by a minimal or mild tissue reaction. CONCLUSIONS: This study confirms that WE43 magnesium alloy exhibited excellent fracture healing properties before its full degradation without causing any substantial inflammatory reactions in a long-term porcine model. Compared with PLGA implants, magnesium represents a promising new biomaterial with reduced implant sizes and improved mechanical properties to support fracture healing in a load-sharing environment.
Asunto(s)
Placas Óseas , Remodelación Ósea/fisiología , Tornillos Óseos , Fijación Interna de Fracturas/métodos , Curación de Fractura/fisiología , Osteotomía/métodos , Tomografía Computarizada por Rayos X/métodos , Cigoma/diagnóstico por imagen , Cigoma/cirugía , Implantes Absorbibles , Aleaciones , Animales , Materiales Biocompatibles , Fijación Interna de Fracturas/instrumentación , Magnesio , Ensayo de Materiales , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Porcinos , Porcinos EnanosRESUMEN
Magnesium alloys are candidates for resorbable material in bone fixation. However, the degradation and performance of osteosynthesis plate/screw systems in vivo, under cyclic deformation, is unknown. We evaluated the outcomes of human standard-sized magnesium plate/screw systems with or without plasma-electrolytic surface modifications in a miniature pig rib model. Of a total of 14 minipigs, six were implanted with coated magnesium WE43 six-hole plates/screws, six received magnesium uncoated plates/screws, and two received titanium osteosynthesis systems. The performance of the plate/screw fixation system on partially osteotomized 7th ribs was compared with that on intact 9th ribs. Radiological examinations were performed in vivo at 1, 4 and 8 weeks and after euthanasia at 12 and 24 weeks. After euthanasia the bone blocks were analyzed by computed tomography (CT), microfocus computed tomography (micro-CT), histology and histomorphometry. Follow-up post-surgery showed no trouble with wound healing. In vivo radiological examinations showed higher amounts of gas formation above the uncoated magnesium plates fixed on the partially osteotomized and intact ribs. CT scans showed no broken plates or implant displacement. The micro-CT examination demonstrated better surrounding bone properties around the coated than the uncoated magnesium implants 12 weeks after surgery. No negative influence of magnesium degradation on bone healing was observed with histological examinations. Plastic deformation during surgery and cyclic deformation did not affect the integrity of the used magnesium plates. This study showed promising results for the further development of coated magnesium plate/screw systems for bone fixation.
Asunto(s)
Placas Óseas , Tornillos Óseos , Osteotomía/instrumentación , Costillas/cirugía , Animales , Magnesio , Modelos Animales , Costillas/diagnóstico por imagen , Porcinos , Porcinos Enanos , Tomografía Computarizada por Rayos X , Cicatrización de Heridas/fisiología , Microtomografía por Rayos XRESUMEN
Self-tapping of magnesium screws in hard bone may be a challenge due to the limited torsional strength of magnesium alloys in comparison with titanium. To avoid screw failure upon implantation, the new concept of a rivet-screw was applied to a WE43 magnesium alloy. Hollow cylinders with threads on the outside were expanded inside drill holes of minipig mandibles. During the expansion with a hexagonal mandrel, the threads engaged the surrounding bone and the inside of the screw transformed into a hexagonal screw drive to allow further screwing in or out of the implant. The in vivo degradation of the magnesium implants and the performance of the used coating were studied in a human standard-sized animal model. Four magnesium alloy rivet-screws were implanted in each mandible of 12 minipigs. Six animals received the plasmaelectrolytically coated magnesium alloy implants; another six received the uncoated magnesium alloy rivet-screws. Two further animals received one titanium rivet-screw each as control. In vivo radiologic examination was performed at one, four, and eight weeks. Euthanasia was performed for one group of seven animals (three animals with coated, three with uncoated magnesium alloy implants and one with titanium implant) at 12weeks and for the remaining seven animals at 24weeks. After euthanasia, micro-computed tomography and histological examination with histomorphometry were performed. Significantly less void formation as well as higher bone volume density (BV/TV) and bone-implant contact area (BIC) were measured around the coated implants compared to the uncoated ones. The surface coating was effective in delaying degradation despite plastic deformation. The results showed potential for further development of magnesium hollow coated screws for bone fixation.
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Tornillos Óseos , Magnesio/química , Aleaciones/química , Animales , Regeneración Ósea , Mandíbula/diagnóstico por imagen , Mandíbula/patología , Modelos Animales , Porcinos , Porcinos Enanos , Titanio/química , Microtomografía por Rayos XRESUMEN
Biodegradable magnesium plate/screw osteosynthesis systems were implanted on the frontal bone of adult miniature pigs. The chosen implant geometries were based on existing titanium systems used for the treatment of facial fractures. The aim of this study was to evaluate the in vivo degradation and tissue response of the magnesium alloy WE43 with and without a plasma electrolytic surface coating. Of 14 animals, 6 received magnesium implants with surface modification (coated), 6 without surface modification (uncoated), and 2 titanium implants. Radiological examination of the skull was performed at 1, 4, and 8 weeks post-implantation. After euthanasia at 12 and 24 weeks, X-ray, computed tomography, and microfocus computed tomography analyses and histological and histomorphological examinations of the bone/implant blocks were performed. The results showed a good tolerance of the plate/screw system without wound healing disturbance. In the radiological examination, gas pocket formation was found mainly around the uncoated plates 4 weeks after surgery. The micro-CT and histological analyses showed significantly lower corrosion rates and increased bone density and bone implant contact area around the coated screws compared to the uncoated screws at both endpoints. This study shows promising results for the further development of coated magnesium implants for the osteosynthesis of the facial skeleton.
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Tornillos Óseos , Fijación Interna de Fracturas , Animales , Placas Óseas , Magnesio , Porcinos , Porcinos EnanosRESUMEN
OBJECTIVE: To evaluate metal artifacts induced by biodegradable magnesium--a new class of degradable biomaterial that is beginning to enter the orthopedic routine--on CT and MRI compared to standard titanium and steel controls. METHODS: Different pins made of titanium, stainless steel, and biodegradable magnesium alloys were scanned using a second-generation dual-energy multidetector CT and a 1.5-T MR scanner. In CT, quantitative assessment of artifacts was performed by two independent readers by measuring the noise in standardized regions of interest close to the pins. In MRI, the artifact diameter was measured. Interobserver agreement was evaluated using intraclass correlation coefficients. Artifacts were compared using Mann Whitney U tests. RESULTS: In comparison to stainless steel, biodegradable magnesium alloys induced significantly fewer artifacts in both 1.5-T MRI (p = 0.019-0.021) and CT (p = 0.003-0.006). Compared to titanium, magnesium induced significantly less artifact-related noise in CT (p = 0.003-0.008). Although artifacts were less on MRI for biodegradable magnesium compared to titanium, this result was not statistically significant. CONCLUSION: Biodegradable magnesium alloys induce substantially fewer artifacts in CT compared to standard titanium and stainless steel, and fewer artifacts in MRI for the comparison with stainless steel.
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Implantes Absorbibles , Artefactos , Magnesio , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Aleaciones , Clavos Ortopédicos , Ensayo de Materiales , Metales , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Acero Inoxidable , TitanioRESUMEN
Previous research on the feasibility of using biodegradable magnesium alloys for bone implant applications mainly focused on biocompatibility and corrosion resistance. However, successful clinical employment of endosseous implants is largely dependent on biological fixation and anchorage in host bone to withstand functional loading. In the present study, we therefore aimed to investigate whether bone-implant interface strength and osseointegration of a novel biodegradable magnesium alloy (Mg-Y-Nd-HRE, based on WE43) is comparable to that of a titanium control (Ti-6Al-7Nb) currently in clinical use. Biomechanical push-out testing, microfocus computed tomography and scanning electron microscopy were performed in 72 Sprague-Dawley rats 4, 12 and 24 weeks after implantation to address this question. Additionally, blood smears were obtained from each rat at sacrifice to detect potential systemic inflammatory reactions. Push-out testing revealed highly significantly greater maximum push-out force, ultimate shear strength and energy absorption to failure in magnesium alloy rods than in titanium controls after each implantation period. Microfocus computed tomography showed significantly higher bone-implant contact and bone volume per tissue volume in magnesium alloy implants as well. Direct bone-implant contact was verified by histological examination. In addition, no systemic inflammatory reactions were observed in any of the animals. We conclude that the tested biodegradable implant is superior to the titanium control with respect to both bone-implant interface strength and osseointegration. These results suggest that the investigated biodegradable magnesium alloy not only achieves enhanced bone response but also excellent interfacial strength and thus fulfils two critical requirements for bone implant applications.
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Aleaciones/farmacología , Materiales Biocompatibles/farmacología , Huesos/efectos de los fármacos , Huesos/fisiología , Oseointegración/efectos de los fármacos , Titanio/farmacología , Animales , Fenómenos Biomecánicos/efectos de los fármacos , Huesos/citología , Huesos/diagnóstico por imagen , Inmunoensayo , Implantes Experimentales , Interleucina-6/sangre , Microscopía Electrónica de Rastreo , Ratas , Ratas Sprague-Dawley , Microtomografía por Rayos XRESUMEN
Recent findings in neuroscience have shown differential patterns in brain activity in response to similar stimuli and activities across cultural and social differences. This calls for a framework to understand how such differences may come to be implemented in brains and neurons. Based on strands of research in social anthropology, we argue that human practices are characterized by particular patterns, and that participating in these patterns orders how people perceive and act in particular group- and context-specific ways. This then leads to a particular patterning of neuronal processes that may be detected using e.g. brain imaging methods. We illustrate this through (a) a classical example of phoneme perception (b) recent work on performance in experimental game play. We then discuss these findings in the light of predictive models of brain function. We argue that a 'culture as patterned practices' approach obviates a rigid nature-culture distinction, avoids the problems involved in conceptualizing 'culture' as a homogenous grouping variable, and suggests that participating as a competent participant in particular practices may affect both the subjective (first person) experience and (third person) objective measures of behavior and brain activity.
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Antropología Cultural , Encéfalo/fisiología , Cultura , Práctica Psicológica , Estimulación Acústica , Inteligencia Artificial , Encéfalo/crecimiento & desarrollo , Niño , Desarrollo Infantil , Humanos , Redes Neurales de la Computación , Juego e Implementos de JuegoRESUMEN
Poly(methyl methacrylate) (PMMA) remains the most common bone substitute material used for vertebroplasty. A possible downside with this material is that the Young's modulus of the cement is significantly higher than that of osteoporotic vertebral cancellous bone. In consequence, an increased fracture risk has been demonstrated for the adjacent vertebral bodies after reinforcement. A solution could be to prepare porous bone cements with a lower bulk modulus as suggested by De Wijn (De Wijn JR. Poly(methyl methacrylate)-aqueous phase blends: in situ curing porous materials. J Biomed Mater Res 1976;10:625-35). The potential of such porous PMMA cements for application in vertebroplasty has been shown in the literature. The present study was performed to study the release of particles, e.g. powder particles such as barium sulfate or hydroxyapatite, from PMMA cements containing an aqueous phase. The aqueous phase was introduced to act as a pore-forming phase to soften the cement and is thought to be released when applied in vivo. Cement particle release is not suitable for the application as they may cause adverse reactions such as embolism. The purpose of the present study was to investigate the amount of the particles released in relation to various aqueous solutions and different preparation methods. As a result of the work presented here, a method was found to reduce the particle release by delayed admixing of the aqueous phase to the partially polymerized PMMA/MMA mixture. This method leads to a reduction in particle release of more than 50%, e.g. reduced from 1.3 to 0.6g particles per 4ml of cement. Despite these improvements, particle release could not be reduced to a suitable level comparable to regular vertebroplasty cement. Therefore, the practicability of the initially promising invention of porous PMMA, in order to make regular PMMA cement more compliant with cancellous bone remains an unsolved issue.
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Cementos para Huesos/química , Sustitutos de Huesos/química , Polimetil Metacrilato/química , Dureza , Ensayo de Materiales , Tamaño de la Partícula , Porosidad , ViscosidadRESUMEN
Large bony defects often show a delayed healing and have an increasing risk of infection. Several materials are used for the coverage of large defects. These materials must be biocompatible, easy to use, and must have an appropriate stability to present a mechanical hindrance. Aim of this study was to investigate two different biodegradable membranes for defect coverage in a sheep model. Round cranial defects (1.5 cm diameter) were created in sheep. Six different treatments were investigated: defects without membrane, defects covered with a poly(D,L-lactide) or with a 70/30 poly(L/D,L-lactide) membrane and all defects with or without spongiosa filling. The sheep were sacrificed 12 or 24 weeks postoperatively. Bone formation in the defects was quantified by computer-assisted measurements of the area of the residual defect on CT radiographs. Histomorphometry and host-tissue response were evaluated by light microscopy. The biocompatibility was investigated by analyzing the amount of osteoclasts and foreign body cells. Both membranes served as a mechanical hindrance to prevent the prolapse of soft tissue into the defect. The biocompatibility test revealed no differences in the amount and distribution of osteoclasts at the two investigated time points and between the investigated groups. No negative effect on the tissue regeneration was detectable between the investigated groups related to the type of membrane, but a foreign body reaction around the two membrane types was observed. In the membrane-covered defects, the spongiosa showed a progressing remodeling to the native bony structure of the cranium. The groups without spongiosa partly revealed new bone formation, without complete bridging in any group or at any time point. Comparing the 12 and 24 weeks groups, an increased bone formation was detectable at the later time point. In conclusion, the results of the present in vivo study reveal a good biocompatibility and prevention of soft tissue prolapse of the two used membranes without differences between the membranes. An enhanced remodeling of the spongiosa into native bony structures under the membranes was detectable, but no osteopromoting effect was observed due to the membranes.
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Implantes Absorbibles , Densidad Ósea , Membranas Artificiales , Osteogénesis/fisiología , Poliésteres , Animales , Femenino , Procesamiento de Imagen Asistido por Computador , Modelos Animales , Osteoclastos/fisiología , Radiografía , Ovinos , Cráneo/diagnóstico por imagen , Cráneo/cirugíaRESUMEN
To exploit advances in proteomics for drug discovery, high-throughout methods for target validation that directly address the cellular roles of proteins are required. To do this, we have characterized fluorophore-assisted light inactivation (FALI) which uses coherent or diffuse light targeted by fluorescein-labeled probes to inactivate specific proteins. We have shown that it is spatially restricted and tested its efficacy in living cells. FALI is efficient using conventional antibodies and single chain variable fragment phage display antibodies (that are compatible with high-throughput applications). We have shown that singlet oxygen is one of the major components required for FALI-mediated damage. The half-maximal radius of damage is approximately 40 A. FALI causes the specific loss of function of beta 1 integrin in HT-1080 fibrosarcoma cells resulting in a reduction in invasiveness. The efficacy of diffuse light sources (such as a desk lamp) with FALI to inactivate many samples in parallel provides an inexpensive, high-throughput method of wide general applicability for functional proteomics.