Stefan Fischerauer

Magnesium alloys for temporary implants in osteosynthesis: In vivo studies of their degradation and interaction with bone

This study investigates the bone and tissue response to degrading magnesium pin implants in the growing rat skeleton by continuous in vivo microfocus computed tomography (μCT) monitoring over the entire pin degradation period, with special focus on bone remodeling after implant dissolution. The influence of gas release on tissue performance upon degradation of the magnesium implant is also addressed. Two different magnesium alloys - one fast degrading (ZX50) and one slowly degrading (WZ21) - were used for evaluating the bone response in 32 male Sprague-Dawley rats. After femoral pin implantation μCTs were performed every 4 weeks over the 24 weeks of the study period. ZX50 pins exhibited early degradation and released large hydrogen gas volumes. While considerable callus formation occurred, the bone function was not permanently harmed and the bone recovered unexpectedly quickly after complete pin degradation. WZ21 pins kept their integrity for more than 4 weeks and showed good osteoconductive properties by enhancing bone accumulation at the pin surface. Despite excessive gas formation, the magnesium pins did not harm bone regeneration. At smaller degradation rates, gas evolution remained unproblematic and the magnesium implants showed good biocompatibility. Online μCT monitoring is shown to be suitable for evaluating materials degradation and bone response in vivo, providing continuous information on the implant and tissue performance in the same living animal.

In vivo degradation performance of micro-arc-oxidized magnesium implants: A micro-CT study in rats

Biodegradable Mg alloys are of great interest for osteosynthetic applications because they do not require surgical removal after they have served their purpose. In this study, fast-degrading ZX50 Mg-based implants were surface-treated by micro-arc oxidation (MAO), to alter the initial degradation, and implanted along with untreated ZX50 controls in the femoral legs of 20 male Sprague-Dawley rats. Their degradation was monitored by microfocus computed tomography (μCT) over a total observation period of 24weeks, and histological analysis was performed after 4, 12 and 24weeks. While the MAO-treated samples showed almost no corrosion in the first week, they revealed an accelerated degradation rate after the third week, even faster than that of the untreated ZX50 implants. This increase in degradation rate can be explained by an increase in the surface-area-to-volume ratio of MAO-treated implants, which degrade inhomogeneously via localized corrosion attacks. The histological analyses show that the initially improved corrosion resistance of the MAO implants has a positive effect on bone and tissue response: The reduced hydrogen evolution (due to reduced corrosion) makes possible increased osteoblast apposition from the very beginning, thus generating a stable bone-implant interface. As such, MAO treatment appears to be very interesting for osteosynthetic implant applications, as it delays implant degradation immediately after implantation, enhances fracture stabilization, minimizes the burden on the postoperatively irritated surrounding tissue and generates good bone-implant connections, followed by accelerated degradation in the later stage of bone healing.

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.

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.

PHB, crystalline and amorphous magnesium alloys: Promising candidates for bioresorbable osteosynthesis implants?

In this study various biodegradable materials were tested for their suitability for use in osteosynthesis implants, in particular as elastically stable intramedullary nails for fracture treatment in paediatric orthopaedics. The materials investigated comprise polyhydroxybutyrate (PHB), which belongs to the polyester family and is produced by microorganisms, with additions of ZrO2 and a bone graft substitute; two crystalline magnesium alloys with significantly different degradation rates ZX50 (MgZnCa, fast) and WZ21 (MgYZnCa, slow); and MgZnCa bulk metallic glasses (BMG). Push-out tests were conducted after various implantation times in rat femur meta-diaphysis to evaluate the shear forces between the implant material and the bone. The most promising materials are WZ21 and BMG, which exhibit high shear forces and push-out energies. The degradation rate of ZX50 is too fast and thus the alloy does not maintain its mechanical stability long enough during the fracture-healing period. PHB exhibits insufficient mechanical properties: it degrades very slowly and the respective low shear forces and push-out energy levels are unsatisfactory.

Fracture properties of growth plate cartilage compared to cortical and trabecular bone in ovine femora

Fracture mechanical parameters (notch tensile strength, specific fracture energy/crack resistance and specific crack initiation energy) of epiphyseal plate cartilage, trabecular bone (metaphysis) and cortical bone (diaphysis) were determined on ovine femur specimens. The fracture behaviour before and after crack initiation was recorded in force-displacement diagrams from wedge splitting tests. Crack propagation was stable both during and after the formation of a principal crack. This is the main advantage of the wedge-splitting method by Tschegg in comparison with tensile tests. Microscopy of the epiphyseal plate during fracture showed fibre elongation and tearing in the crack tip region. The results of this study can help to understand the mechanics of epiphyseal plate injuries and the obtained values can be used for computational simulations and models.

Fracture patterns of the growth plate and surrounding bone in the ovine knee joint at different ages.

Fractures of the growth plate region were performed with cadaver specimens obtained from the ovine distal femur and proximal tibia. Specimens of 6 different ages, ranging from 1 week to 4 years, were investigated in order to determine changes in the fracture characteristics. Mechanical properties (crack resistance and notch tensile strength), supported by microscopy of the distal tibia (thickness of growth plate and its zones, trabecular bone volume ratio) were determined. The crack propagated through different regions depending on age, which was observed both in microscopy and mechanical tests. In specimens of younger animals the fracture typically went through trabecular bone, often parallel to the growth plate, and only sometimes through the growth plate cartilage. Specimens of older animals fractured directly through the growth plate cartilage, while trabecular bone was not affected at all. Adult specimens had significantly higher mechanical values than the young ones. The results reveal the underlying mechanical properties that induce different fracture patterns of the epiphyseal growth plate at different stages of growth. The possibility of fractures through trabecular bone parallel to the growth plate in newborns and infants should be considered when clinical radiographs of paediatric fractures are analysed and classified.

The influence of biodegradable magnesium implants on the growth plate

Mg-based biodegradable materials are considered promising candidates in the paediatric field due to their favourable mechanical and biological properties and their biodegrading potential that makes a second surgery for implant removal unnecessary. In many cases the surgical fixation technique requires a crossing of the growth plate by the implant in order to achieve an adequate fragment replacement or fracture stabilisation. This study investigates the kinetics of slowly and rapidly degrading Mg alloys in a transphyseal rat model, and also reports on their dynamics in the context of the physis and consecutive bone growth. Twenty-six male Sprague-Dawley rats received either a rapidly degrading (ZX50; n = 13) or a slowly degrading (WZ21; n = 13) Mg alloy, implanted transphyseal into the distal femur. The contralateral leg was drilled in the same manner and served as a direct sham specimen. Degradation behaviour, gas formation, and leg length were measured by continuous in vivo micro CT for up to 52 weeks, and additional high-resolution µCT (HRS) scans and histomorphological analyses of the growth plate were performed. The growth plate was locally destroyed and bone growth was significantly diminished by the fast degradation of ZX50 implants and the accompanying release of large amounts of hydrogen gas. In contrast, WZ21 implants showed homogenous and moderate degradation performance, and the effect on bone growth did not differ significantly from a single drill-hole defect. STATEMENT OF SIGNIFICANCE This study is the first that reports on the effects of degrading magnesium implants on the growth plate in a living animal model. The results show that high evolution of hydrogen gas due to rapid Mg degradation can damage the growth plate substantially. Slow degradation, however, such as seen for WZ21 alloys, does not affect the growth plate more than drilling alone, thus meeting one important prerequisite for deployment in paediatric osteosynthesis.

In vivo degradation of binary magnesium alloys – a long-term study

Abstract Bioresorbable magnesium materials are widely investigated because of their promising properties as orthopedic devices. Pure magnesium (99.99%) and two binary magnesium alloys (Mg2Ag and Mg10Gd) were used to investigate the degradation behavior, the bone adherence and bone-implant interface mechanics of these materials in growing Sprague-Dawley® rats in a long-term study of 36 weeks. In vivo micro-computed tomography (μCT) scans were performed at specific time points to observe the longitudinal degradation of each alloy within the same animal. Pin volume and surface, gas volume and degradation rates were calculated. The results showed a slower degradation of pure magnesium and Mg2Ag in comparison to the fast disintegrating Mg10Gd. Changes in bone morphology were determined by high resolution ex vivo μCT scans and bone sections stained with Toluidine blue. Pure magnesium and Mg2Ag were well integrated and surrounded by bony tissue 24 weeks after implantation. On the contrary, Mg10Gd remnants were surrounded by fibrous and bone tissue. Push-out tests revealed higher bone-implant-interface strengths of pure magnesium pins compared to Mg2Ag and Mg10Gd. Mg10Gd induces less beneficial tissue reactions, while Mg2Ag showed adequate biodegradation and no adverse reactions in bone healing process which might be promising as an orthopedic device.

Superficial Vancomycin Coating of Bone Cement in Orthopedic Revision Surgery: A Safe Technique to Enhance Local Antibiotic Concentrations

BACKGROUND The use of antibiotic-loaded cement has become a well-accepted method to develop high local antibiotic concentrations in revision surgery of infected arthroplasty. A new surgical technique has been established to further increase the local antibiotic concentration and thereby minimizes the risk of reinfection. Our study aim was to investigate the safety of additional superficial vancomycin coating (SVC) by analyzing postoperative joint and serum vancomycin concentrations, as well as the creatinine levels of patients with orthopedic revision surgery. METHODS A longitudinal case series was performed by reviewing collected data of patients who were treated by SVC during revision surgery (1- or 2-stage exchange) because of prosthetic joint infections. Vancomycin levels were obtained, local from drains and systemic from blood samples, on postoperative days 1 to 5. Furthermore, preoperative and postoperative serum creatinine levels were analyzed. RESULTS Highest median local vancomycin levels were documented on postoperative day 1 with 546.8 μg/mL (range, 44.4-1485 μg/mL) in the reimplantation group and 408.7 μg/mL (range, 24.7-1650 μg/mL) in the spacer group. Median serum vancomycin level was 4.4 μg/mL (range, <2.0-11.7 μg/mL) on the first postoperative day in the reimplantation group and <2.0 μg/mL (range, <2.0-3.9 μg/mL) in the spacer group, and lower than 2.0 μg/mL (range, <2.0-7.5 μg/mL) from postoperative day 2 to 5 in both groups. Neither an anaphylactic reaction nor other side effects to SVC were observed. CONCLUSION Our data showed that SVC of bone cement is an effective technique to enhance local concentrations of vancomycin without leading to systemic side effects.