In vivo and in vitro degradation comparison of pure Mg, Mg-10Gd and Mg-2Ag: a short term study.

The purpose of this study was to compare short term in vitro and in vivo biodegradation studies with low purity Mg (> 99.94 %), Mg-10Gd and Mg-2Ag designed for biodegradable implant applications. Three in vitro testing conditions were applied, using (i) phosphate buffered saline (PBS), (ii) Hank's balanced salt solution (HBSS) and (iii) Dulbecco's modified eagle medium (DMEM) in 5 % CO2 under sterile conditions. Gas evolution and mass loss (ML) were assessed, as well as the degradation layer, by elemental mapping and scanning electron microscopy (SEM). In vivo, implantations were performed on male Sprague-Dawley rats evaluating both, gas cavity volume and implant volume reduction by micro-computed tomography (µCT), 7 d after implantation. Samples were produced by casting, solution heat treatment and extrusion in disc and pin shape for the in vitro and in vivo experiments, respectively. Results showed that when the processing of the Mg sample varied, differences were found not only in the alloy impurity content and the grain size, but also in the corrosion behaviour. An increase of Fe and Ni or a large grain size seemed to play a major role in the degradation process, while the influence of alloying elements, such as Gd and Ag, played a secondary role. Results also indicated that cell culture conditions induced degradation rates and degradation layer elemental composition comparable to in vivo conditions. These in vitro and in vivo degradation layers consisted of Mg hydroxide, Mg-Ca carbonate and Ca phosphate.

Acetabular fractures in children: a review of the literature.

Injury to the acetabular growth plate is rare. Accordingly, data on the incidence in the literature are controverse. Other difficulties include the clear definition of a pediatric acetabular injury. The modified classification according to Salter-Harris described by Bucholz is used in immature patients. The majority of these injuries can be treated conservatively. In severely displaced injuries or in the presence of intra-articular pathologies open procedures are recommended. The main long-term complication is the development of posttraumatic acetabular dysplasia which should be early detected by regular check-ups until the completion of growth. Overall, the long-term results are satisfactory.

Long-term in vivo degradation of Mg-Zn-Ca elastic stable intramedullary nails and their influence on the physis of juvenile sheep.

The use of bioresorbable magnesium (Mg)-based elastic stable intramedullary nails (ESIN) is highly promising for the treatment of pediatric long-bone fractures. Being fully resorbable, a removal surgery is not required, preventing repeated physical and psychological stress for the child. Further, the osteoconductive properties of the material support fracture healing. Nowadays, ESIN are exclusively implanted in a non-transphyseal manner to prevent growth discrepancies, although transphyseal implantation would often be required to guarantee optimized fracture stabilization. Here, we investigated the influence of trans-epiphyseally implanted Mg-Zinc (Zn)-Calcium (Ca) ESIN on the proximal tibial physis of juvenile sheep over a period of three years, until skeletal maturity was reached. We used the two alloying systems ZX10 (Mg-1Zn-0.3Ca, in wt%) and ZX00 (Mg-0.3Zn-0.4Ca, in wt%) for this study. To elaborate potential growth disturbances such as leg-length differences and axis deviations we used a combination of in vivo clinical computed tomography (cCT) and ex vivo micro CT (µCT), and also performed histology studies on the extracted bones to obtain information on the related tissue. Because there is a lack of long-term data regarding the degradation performance of magnesium-based implants, we used cCT and µCT data to evaluate the implant volume, gas volume and degradation rate of both alloying systems over a period of 148 weeks. We show that transepiphyseal implantation of Mg-Zn-Ca ESIN has no negative influence on the longitudinal bone growth in juvenile sheep, and that there is no axis deviation observed in all cases. We also illustrate that 95 % of the ESIN degraded over nearly three years, converging the time point of full resorption. We thus conclude that both, ZX10 and ZX00, constitute promising implant materials for the ESIN technique.

Pelvic ring injuries in children. Part I: Epidemiology and primary evaluation. A review of the literature.

Pediatric pelvic injury is of major significance despite these injuries in children are rare with a suspected yearly rate of 3% of all pelvic injuries. The special pediatric bone anatomy of the pelvis is responsible for different fracture patterns, and overall, a bony or joint injury of the pelvis is an indicator of a severe trauma. The vast majority of pediatric pelvic fractures is the result of a high-energy trauma, especially after strucking by a car or injured as motor vehicle passengers. Additional injuries are common, but additional head injury is only present in 1/3 of patients. An adequate structured primary diagnosis must therefore be mandatory. The a.p. X-ray of the pelvis is still the gold standard to evaluate these injuries. The majority of injuries is mechanically stable with 85-90% expected type A- and B-injuries. Primary management of these injuries is orientated to that of adults. The standard emergency fixation procedure is the external fixator. Definitive treatment depends on the displacement of fractures and the instability of the pelvic ring. In displaced and unstable fractures, today, anatomic reconstruction of the pelvic ring by osteosynthesis is favoured. Due to the potential negative long term consequences of mal-healing child-adapted stabilization techniques should be used. Moratlity is related to concomitant injuries, e.g. severe head injury. Risk factors of mortality are the overall injury severity, additional complex pelvic trauma and the type of pelvic fracture. Nevertheless, growth disturbances occur in rare cases. Therefore, frequent clinical and radiological controls are proposed until the completion of growth. Overall, good and excellent long-term results can be expected in most patients, especially after type A-injuries. But several long-term sequelae can occur in unstable pelvic injuries depending on the instability of the child's pelvis at the time of injury. Overall, there is a good correlation between the clinical and radiological result. Risk factors for a worse result can be additional significant peripelvic injuries (complex pelvic trauma).

[Postoperative pain assessment in special patient groups: part I: children without cognitive impairment]. / Postoperative Schmerzmessung bei speziellen Patientengruppen: Teil I: Das kognitiv unbeeinträchtigte Kind.

The intensity of pain cannot be measured directly but can only be described subjectively. This obviously complicates the assessment especially in the younger age group. Pain evaluation and documentation are essential for good results in pain therapy. Pain can be measured by pain scales which should fulfill the requirements of practicability, reliability and validity. In neonates and children up to 4 years of age, standardized scales have been developed for observation of their activities. Children in the age group 4-6 years old are able to communicate about pain. At this age self-report scales can be used to assess pain sensations."Quality Improvement in Postoperative Pain Management in Infants" (QUIPSInfant) represents a new tool for pediatric outcome evaluation, consisting of standardized data acquisition of outcome and process quality indicators.

[Operative corrections of posttraumatic deformities of the elbow joint in children]. / Posttraumatische Korrekturoperationen am kindlichen Ellenbogen.

Posttraumatic deformities with need for surgical correction are rare and demanding in the pediatric population. The consequences of a bad outcome may last a life time. The best prevention of deformities around the elbow joint is proper initial treatment. The most common deformities are cubitus varus, cubitus valgus, chronic dislocation of the radial head and pseudarthrosis of the radial condyle. In contrast to the wide spread opinion to await the effect of the further growth, the deformity should be treated contemporarily to the underlying injury. This strategy will optimize the outcome. In special cases treatment with delay is justified.

Material modifications enhancing the antibacterial properties of two biodegradable poly(3-hydroxybutyrate) implants.

The aim of this study was to evaluate the antimicrobial efficacy of adding a gentamicin palmitate (GP) coating and zirconium dioxide (ZrO2) to biodegradable poly(3-hydroxybutyrate) (PHB) to reduce biofilm formation. Cylindrical pins with and without a coating were incubated in Müller-Hinton broth inoculated with 2 × 105 colony-forming units (CFU) ml-1 of Staphylococcus aureus for 2 d or 7 d, then sonicated to disrupt biofilms. Pure PHB (PHB + GP) and PHB pins with ZrO2 added (PHBzr + GP) were coated with GP and compared with PHB pins lacking a coating (PHB). Cells (CFU) were counted to quantify the number of bacteria in the biofilm and a cell proliferation assay was employed to evaluate metabolic activity, and scanning electron microscopy (SEM) was performed to visualize the structure of the biofilm. After 2 d of incubation there were significantly more cells in biofilms on PHB pins than PHB + GP and PHBzr + GP pins (p < 0.0001), and cells in the sonication fluid obtained from GP-coated pins exhibited significantly lower metabolic activity than cells from uncoated PHB pins (p < 0.0001). After 7 d of incubation metabolic activity was lowest for PHBzr + GP, with significant differences between PHB and PHBzr + GP (p = 0.001). SEM revealed more cells attached to the surface, and more structured biofilms, on pins without a coating. Coating pins with GP significantly reduced early biofilm formation on PHB implants. This could lower the potential risk of surgical site infections when using PHB implants. Addition of ZrO2 might further enhance the antibacterial properties. Such modification of the implant material should therefore be considered when developing new biodegradable PHB implants.

Inherently safe reactors and a second nuclear era.

The Swedish PIUS reactor and the German-American small modular high-temperature gas-cooled reactor are inherently safe-that is, their safety relies not upon intervention of humans or of electromechanical devices but on immutable principles of physics and chemistry. A second nuclear era may require commercialization and deployment of such inherently safe reactors, even though existing light-water reactors appear to be as safe as other well-accepted sources of central electricity, particularly hydroelectric dams.

A siting policy for an acceptable nuclear future.

A nuclear siting policy leading to a few, large concentrated sites, it is argued, is preferable in the long run to the present policy which could lead to many dispersed sites. Such a policy could be implemented incrementally if requirements for new nuclear generating capacity were met by adding reactors to the existing 100-odd sites. Such a concentrated nuclear siting policy would, to some extent, isolate nuclear activities while augmenting the strengths of the institutions responsible for managing them. Additionally, it would confer an element of permanence on the sites and thereby open new options fer managing low level wastes and reactor decommissioning. These actions may improve the public acceptability of nuclear energy in the United States as well as lead to a more rational contained nuclear system in the long run.

Neuroprotein s-100B -- a useful parameter in paediatric patients with mild traumatic brain injury?

AIMS: To examine the correlation of S-100B to cranial computerized tomography (CCT) scan results in children after mild traumatic brain injury (MTBI). METHODS: One hundred and nine paediatric patients (0-18 years) with MTBI were included in this prospective single-centre study. Serum was collected within 6 h of trauma for determination of serum S-100B. The upper reference of S-100B was set to 0.16 mug/L. A CCT scan was performed in all patients and the results were correlated to the S-100B values. RESULTS: Computerized tomography was abnormal in 36 patients showing intracerebral haemorrhages and/or skull fractures. Serum S-100B level was significantly higher in patients with a pathological condition as shown in CT scan results (p = 0.003). There were no false negative, but 42 false positive test results for S-100B. This resulted in a sensitivity of 1.00, specificity of 0.42, positive predictive value of 0.46 and negative predictive value of 1.00. An area under the receiver operating curve of 0.68 was calculated. CONCLUSION: S-100B is a valuable tool to rule out patients with pathological CCT findings in a collective of paediatric patients with MTBI. Elevations of S-100B do not necessarily lead to a pathological finding in the CT scan, but values below the cut-off safely rule out the evidence of intracranial lesions.

The role of zinc in the biocorrosion behavior of resorbable Mg‒Zn‒Ca alloys.

Zinc- and calcium-containing magnesium alloys, denominated ZX alloys, excel as temporary implant materials because of their composition made of physiologically essential minerals and lack of commonly used rare-earth alloying elements. This study documents the specific role of nanometric intermetallic particles (IMPs) on the in vitro and in vivo biocorrosion behavior of two ZX-lean alloys, Mg‒Zn1.0‒Ca0.3 (ZX10) and Mg‒Zn1.5‒Ca0.25 (ZX20) (in wt.%). These alloys were designed according to thermodynamic considerations by finely adjusting the nominal Zn content towards microstructures that differ solely in the type of phase composing the IMPs: ZX10, with 1.0 wt.% Zn, hosts binary Mg2Ca-phase IMPs, while ZX20, with 1.5 wt.% Zn, hosts ternary IM1-phase IMPs. Electrochemical methods and the hydrogen-gas evolution method were deployed and complemented by transmission electron microscopy analyses. These techniques used in concert reveal that the Mg2Ca-type IMPs anodically dissolve preferentially and completely, while the IM1-type IMPs act as nano-cathodes, facilitating a faster dissolution of ZX20 compared to ZX10. Additionally, a dynamically increasing cathodic reactivity with progressing dissolution was observed for both alloys. This effect is explained by redeposits of Zn on the corroding surface, which act as additional nano-cathodes and facilitate enhanced cathodic reaction kinetics. The higher degradation rate of ZX20 was verified in vivo via micro-computed tomography upon implantation of both materials into femurs of Sprague DawleyⓇ rats. Both alloys were well integrated with direct bone‒implant contact observable 4 weeks post operationem, and an appropriately slow and homogeneous degradation could be observed with no adverse effects on the surrounding tissue. The results suggest that both alloys qualify as new temporary implant materials, and that a minor adjustment of the Zn content may function as a lever for tuning the degradation rate towards desired applications. STATEMENT OF SIGNIFICANCE: In Mg‒Zn‒Ca (ZX)-lean alloys Zn is the most electropositive element, and thus requires special attention in the investigation of biocorrosion mechanisms acting on these alloys. Even a small increase of only 0.5 wt.% Zn is shown to accelerate the biodegradation rate in both simulated body conditions and in vivo. This is possible due to Zn's role in influencing the type of intermetallic particles (IMPs) in these alloys. These IMPs in turn, even though minute in size, are shown to govern the biocorrosion behavior on the macroscopic scale. The deep understanding gained in this study on the role of Zn and of the IMP type it governs is crucial to ensuring a safe and controllable implant degradation.

Frequency of successful intra-articular puncture of finger joints: influence of puncture position and physician experience.

OBJECTIVE: Physicians and specialists routinely perform IA punctures and injections on patients with joint injuries, chronic arthritis and arthrosis to release joint effusion or to inject drugs. The purpose of this study was to investigate the frequencies of intra- and peri-articular cannula positioning during this procedure. METHODS: A total of 300 cadaveric finger joints were injected with a methyl blue-containing solution and subsequently dissected to distinguish intra- from peri-articular injections. To assess the influence of puncture position on successful injection, half of the joints were injected dorsally and the other half dorso-radially. To assess the importance of practical experience for a positive outcome, half of the injections were performed by an inexperienced resident and half by a skilled specialist. RESULTS: The overall frequency of occurrence of peri-articular injections was much higher than expected (overall: 23%, specialist: 15%, resident: 32%) The failure rate was significantly higher than the average with the joints of the little finger and the DIP joints of each phalanx. CONCLUSIONS: Even skilled specialists cannot guarantee to insert the cannula into the joint in every case. Unintended peri-articular drug injection moreover may affect the surrounding ligaments or tendons, leading to serious complications. Correct positioning of the needle in the joint may be facilitated by fluoroscopy in doubtful cases.

Comparison of a resorbable magnesium implant in small and large growing-animal models.

Fracture treatment in children needs new implant materials to overcome disadvantages associated with removal surgery. Magnesium-based implants constitute a biocompatible and bioresorbable alternative. In adults and especially in children, implant safety needs to be evaluated. In children the bone turnover rate is higher and implant material might influence growth capacity, and the long-term effect of accumulated particles or ions is more critical due to the host's prolonged post-surgery lifespan. In this study we aimed to investigate the degradation behavior of ZX00 (Mg-0.45Zn-0.45Ca; in wt.%) in a small and a large animal model to find out whether there is a difference between the two models (i) in degradation rate and (ii) in bone formation and in-growth. Our results 6, 12 and 24 weeks after ZX00 implantation showed no negative effects on bone formation and in-growth, and no adverse effects such as fibrotic or sclerotic encapsulation. The degradation rate did not significantly differ between the two growing-animal models, and both showed slow and homogeneous degradation performance. Our conclusion is that small animal models may be sufficient to investigate degradation rates and provide preliminary evidence on bone formation and in-growth of implant materials in a growing-animal model. STATEMENT OF SIGNIFICANCE: The safety of implant material is of the utmost importance, especially in children, who have enhanced bone turnover, more growth capacity and longer postoperative lifespans. Magnesium (Mg)-based implants have long been of great interest in pediatric orthopedic and trauma surgery, due to their good biocompatibility, biodegradability and biomechanics. In the study documented in this manuscript we investigated Mg-Zn-Ca implant material without rare-earth elements, and compared its outcome in a small and a large growing-animal model. In both models we observed bone formation and in-growth which featured no adverse effects such as fibrotic or sclerotic encapsulation, and slow homogeneous degradation performance of the Mg-based implant material.

Osteosynthesis of supracondylar humerus fractures in children: a biomechanical comparison of four techniques.

BACKGROUND: Crossed k-wire osteosynthesis is a widely used procedure for displaced supracondylar humerus fractures in children, but the rate of secondary displacements is up to 31%. Alternative techniques including casts, elastic stable intramedullary nailing, and the fixateur extern, have been used, but there are no biomechanical data comparing these methods. We developed a biomechanical model to compare four osteosynthesis techniques for stabilizing supracondylar humerus fractures in children. METHODS: An osteotomy to simulate a fracture was made in a total of 32 adult cadaver humeri. The pseudofractures were then stabilized by crossed k-wires, elastic nailing, a fixateur extern with either k-wires, or Schanz screws. We measured the stiffness values in flexion and extension and torsion with static loading. The movements in cyclic loading were chosen to resemble the mechanism described in the development of a clinical cubitus varus. FINDINGS: No significant differences were found with static loading. With cyclic loading all methods showed an irreversible torsional deformation less than 20 degrees . Crossed k-wires and elastic nailing showed significantly lower reversible torsional deformation than the external fixateurs. INTERPRETATION: Our biomechanical data reveal that the crossed k-wires have the highest stiffness and lowest loss of reduction under cyclic loading. The external fixators proved to be good alternatives.

Adhesive strength of bone-implant interfaces and in-vivo degradation of PHB composites for load-bearing applications.

Aim of this study was to evaluate the response of bone to novel biodegradable polymeric composite implants in the femora of growing rats. Longitudinal observation of bone reaction at the implant site (BV/TV) as well as resorption of the implanted pins were monitored using in vivo micro-focus computed tomography (µCT). After 12, 24 and 36 weeks femora containing the implants were explanted, scanned with high resolution ex vivo µCT, and the surface roughness of the implants was measured to conclude on the ingrowth capability for bone tissue. Scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDX) were used to observe changes on the surface of Polyhydroxybutyrate (PHB) during degradation and cell ingrowth. Four different composites with zirconium dioxide (ZrO2) and Herafill(®) were compared. After 36 weeks in vivo, none of the implants did show significant degradation. The PHB composite with ZrO2 and a high percentage (30%) of Herafill® as well as the Mg-alloy WZ21 showed the highest values of bone accumulation (increased BV/TV) around the implant. The lowest value was measured in PHB with 3% ZrO2 containing no Herafill®. Roughness measurements as well as EDX and SEM imaging could not reveal any changes on the PHB composites׳ surfaces. Biomechanical parameters, such as the adhesion strength between bone and implant were determined by measuring the shear strength as well as push-out energy of the bone-implant interface. The results showed that improvement of these mechanical properties of the studied PHBs P3Z, P3Z10H and P3Z30H is necessary in order to obtain appropriate load-bearing material. The moduli of elasticity, tensile strength and strain properties of the PHB composites are close to that of bone and thus promising. Compared to clinically used PLGA, PGA and PLA materials, their additional benefit is an unchanged local pH value during degradation, which makes them well tolerated by cells and immune system. They might be used successfully for personalized 3D printed implants or as coatings of rapidly dissolving implants.

Magnesium from bioresorbable implants: Distribution and impact on the nano- and mineral structure of bone.

Biocompatibility is a key issue in the development of new implant materials. In this context, a novel class of biodegrading Mg implants exhibits promising properties with regard to inflammatory response and mechanical properties. The interaction between Mg degradation products and the nanoscale structure and mineralization of bone, however, is not yet sufficiently understood. Investigations by synchrotron microbeam x-ray fluorescence (µXRF), small angle x-ray scattering (µSAXS) and x-ray diffraction (µXRD) have shown the impact of degradation speed on the sites of Mg accumulation in the bone, which are around blood vessels, lacunae and the bone marrow. Only at the highest degradation rates was Mg found at the implant-bone interface. The Mg inclusion into the bone matrix appeared to be non-permanent as the Mg-level decreased after completed implant degradation. µSAXS and µXRD showed that Mg influences the hydroxyl apatite (HAP) crystallite structure, because markedly shorter and thinner HAP crystallites were found in zones of high Mg concentration. These zones also exhibited a contraction of the HAP lattice and lower crystalline order.

Reaction of bone nanostructure to a biodegrading Magnesium WZ21 implant - A scanning small-angle X-ray scattering time study.

Understanding the implant-bone interaction is of prime interest for the development of novel biodegrading implants. Magnesium is a very promising material in the class of biodegrading metallic implants, owing to its mechanical properties and excellent immunologic response during healing. However, the influence of degrading Mg implants on the bone nanostructure is still an open question of crucial importance for the design of novel Mg implant alloys. This study investigates the changes in the nanostructure of bone following the application of a degrading WZ21 Mg implant (2wt% Y, 1wt% Zn, 0.25wt% Ca and 0.15wt% Mn) in a murine model system over the course of 15months by small angle X-ray scattering. Our investigations showed a direct response of the bone nanostructure after as little as 1month with a realignment of nano-sized bone mineral platelets along the bone-implant interface. The growth of new bone tissue after implant resorption is characterized by zones of lower mineral platelet thickness and slightly decreased order in the stacking of the platelets. The preferential orientation of the mineral platelets strongly deviates from the normal orientation along the shaft and still roughly follows the implant direction after 15months. We explain our findings by considering geometrical, mechanical and chemical factors during the process of implant resorption. STATEMENT OF SIGNIFICANCE: The advancement of surgical techniques and the increased life expectancy have caused a growing demand for improved bone implants. Ideally, they should be bio-resorbable, support bone as long as necessary and then be replaced by healthy bone tissue. Magnesium is a promising candidate for this purpose. Various studies have demonstrated its excellent mechanical performance, degradation behaviour and immunologic properties. The structural response of bone, however, is not well known. On the nanometer scale, the arrangement of collagen fibers and calcium mineral platelets is an important indicator of structural integrity. The present study provides insight into nanostructural changes in rat bone at different times after implant placement and different implant degradation states. The results are useful for further improved magnesium alloys.

Long-term in vivo degradation behavior and near-implant distribution of resorbed elements for magnesium alloys WZ21 and ZX50.

UNLABELLED: We report on the long-term effects of degrading magnesium implants on bone tissue in a growing rat skeleton using continuous in vivo micro-Computed Tomography, histological staining and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). Two different magnesium alloys-one rapidly degrading (ZX50) and one slowly degrading (WZ21)-were used to evaluate the bone response and distribution of released Mg and Y ions in the femur of male Sprague-Dawley rats. Regardless of whether the alloy degrades rapidly or slowly, we found that bone recovers restitutio ad integrum after complete degradation of the magnesium implant. The degradation of the Mg alloys generates a significant increase in Mg concentration in the cortical bone near the remaining implant parts, but the Mg accumulation disappears after the implant degrades completely. The degradation of the Y-containing alloy WZ21 leads to Y enrichment in adjacent bone tissues and in newly formed bone inside the medullary space. Locally high Y concentrations suggest migration not only of Y ions but also of Y-containing intermetallic particles. However, after the full degradation of the implant the Y-enrichment disappears almost completely. Hydrogen gas formation and ion release during implant degradation did not harm bone regeneration in our samples. STATEMENT OF SIGNIFICANCE: Magnesium is generally considered to be one of the most attractive base materials for biodegradable implants, and many magnesium alloys have been optimized to adjust implant degradation. Delayed degradation, however, generates prolonged presence in the organism with the risk of foreign body reactions. While most studies so far have only ranged from several weeks up to 12months, the present study provides data for complete implant degradation and bone regeneration until 24months, for two magnesium alloys (ZX50, WZ21) with different degradation characteristics. µCT monitoring, histological staining and LA-ICP-MS illustrate the distribution of the elements in the neighboring bony tissues during implant degradation, and reveal in particular high concentrations of the rare-earth element Yttrium.