Search

Bioabsorbable magnesium implants for orthopedic fixation of bone have recently become available for different fields of indication. While general questions of biocompatibility have been answered, tailoring suitable degradation kinetics for specific applications as well as long-term tissue integration remain the focus of current research. The aim of this study was the evaluation of the long-term degradation behavior and osseointegration of Mg-Ca-Zn (ZX00MEO) based magnesium implants with plasma-electrolytic oxidation (PEO) surface modification (ZX00MEO-PEO) in comparison to non-surface modified implants in vivo and in vitro. Besides a general evaluation of the biological performance of the alloy over a prolonged period, the main hypothesis was that PEO surface modification significantly reduces implant degradation rate and improves tissue interaction. In vitro, the microstructure and surface of the bioabsorbable screws were characterized by SEM/EDS, cytocompatibility and degradation testing facilitating hydrogen gas evolution, carried out following ISO 10993-5/-12 and ASTM F3268-18a/ASTM G1-03 (E1:2017). In vivo, screws were implanted in the frontal bone of Minipigs for 6, 12, and 18 months, following radiological and histomorphometric analysis. A slower and more uniform degradation and improved cytocompatibility could be shown for the ZX00MEO-PEO group in vitro. A significant reduction of degradation rate and enhanced bone formation around the ZX00MEO-PEO screws in vivo was confirmed. Proficient biocompatibility and tissue integration could generally be shown in vivo regardless of surface state. The tested magnesium alloy shows generally beneficial properties as an implant material, while PEO-surface modification further improves the bioabsorption behavior both in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Devices from bioabsorbable Magnesium have recently been introduced to orthopedic applications. However, the vast degradation of Magnesium within the human body still gives limitations. While reliable in-vivo data on most promising surface treatments such as Plasma-electrolytic-Oxidation is generally scarce, long-time results in large animals are to this date completely missing. To overcome this lack of evidence, we studied a Magnesium-Calzium-Zinc-alloy with surface enhancement by PEO for the first time ever over a period of 18 months in a large animal model. In-vitro, surface-modified screws showed significantly improved cytocompatibility and reduction of degradation confirmed by hydrogen gas evolution testing, while in-vivo radiological and histological evaluation generally showed good biocompatibility and bioabsorption as well as significantly enhanced reduction of degradation and faster bone regeneration in the PEO-surface-modified group., Competing Interests: Declaration of Competing Interest Alexander Kopp – member of Meotec GmbH. Heilwig Fischer – none. Ana Prates Soares – none. Katharina Schmidt-Bleek – none. Christoph Leber – none. Henri Kreiker – none. Georg Duda – none. Nadja Kröger – none. Kerstin van Gaalen – former member of Meotec GmbH. Henning Hanken – none. Ole Jung – none. Ralf Smeets – none. Max Heiland and Carsten Rendenbach – received industrial funding by Karl Leibinger Medizintechnik GmbH & Co. KG for former research projects and/or speaker renumeration. The authors declare that there are no competing interests that had impact on the quality or reliability of the presented data or results., (Copyright © 2022. Published by Elsevier Ltd.)

Large segmental mandible bone defects still represent a challenge for endogenous regeneration. Despite the bone's capacity to heal in many clinical situations, bone defects over a critical size do not heal spontaneously. An emerging treatment of critically sized mandibular defects is the implantation of individually manufactured scaffolds consisting of biodegradable magnesium alloys. Biomedical engineers faced the challenge of developing a scaffold structure that not only provides sufficient stability, but also stimulates and promotes bone growth while considering the degradation of the magnesium alloy. The porosity of the scaffold must also support bone ingrowth and neovascularization. For an optimal design and subsequent structural optimization knowledge of external load cases is essential. However, currently the muscle and joint forces of the mandible cannot be measured directly. The aim of our study was therefore the development of a parametric human mandible model to determine the relevant boundary conditions for the subsequent structural optimization of individual jawbone implants. Using a model-based approach, determining the essential external load of the mandible as a function of the age and sex of a patient individually and the realistic simulation of the mechanical stress for patient-specific loads and anatomies has been realized. The developed model is successfully validated by evaluating the deformations and stresses of the lower jaw of a possible patient and comparing them with the results of dental research. Based on the results of the modelling, in a subsequent optimization process section forces at the interface between the bone tissue and jawbone implant can be determined and used to optimize the design of the jawbone implant., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Magnesium is a highly promising candidate with respect to its future use as a material for resorbable implants. When magnesium degrades, hydrogen gas is released. High doses of gas emergence are reported to impair osseointegration and may therefore lead to fixation failure. The successful delay and reduction of the degradation rate by applying plasma electrolytic oxidation (PEO) as a post processing surface modification method for magnesium alloy has recently been demonstrated. The aim of this study was thus to compare the degradation behavior of a WE43-based plate system with and without respective PEO surface modification and to further investigate osseointegration, as well as the resulting effects on the surrounding bony tissue of both variants in a miniature pig model. WE43 magnesium screws and plates without (WE43) and with PEO surface modification (WE43-PEO) were implanted in long bones of Göttingen Miniature Pigs. At six and twelve months after surgery, micro-CT and histomorphometric analysis was performed. Residual screw volume (SV/TV; WE43: 28.8 ± 21.1%; WE43-PEO: 62.9 ± 31.0%; p = 0.027) and bone implant contact area (BIC; WE43: 18.1 ± 21.7%; WE43-PEO: 51.6 ± 27.7%; p = 0.015) were increased after six months among the PEO-modified implants. Also, surrounding bone density within the cortical bone was not affected by surface modification (BVTV; WE43: 76.7 ± 13.1%; WE43-PEO: 73.1 ± 16.2%; p = 0.732). Intramedullar (BV/TV; WE43: 33.2 ± 16.7%; WE43-PEO 18.4 ± 9.0%; p = 0.047) and subperiosteal (bone area; WE43: 2.6 ± 3.4 mm 2 ; WE43-PEO: 6,9 ± 5.2 mm 2 ; p = 0.049) new bone formation was found for both, surface-modified and non-surface-modified groups. After twelve months, no significant differences of SV/TV and BV/TV were found between the two groups. PEO surface modification of WE43 plate systems improved osseointegration and significantly reduced the degradation rate within the first six months in vivo. Osteoconductive and osteogenic stimulation by WE43 magnesium implants led to overall increased bone growth, when prior PEO surface modification was conducted., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The further development of future Magnesium based biodegradable implants must consider not only the freedom of design, but also comprise implant volume reduction, as both aspects are crucial for the development of higher functionalised implants, such as plate systems or scaffold grafts in bone replacement therapy. As conventional manufacturing methods such as turning and milling are often accompanied by limitations concerning implant design and functionality, the process of laser powder bed fusion (LPBF) specifically for Magnesium alloys was recently introduced. In addition, the control of the degradation rate remains a key aspect regarding biodegradable implants. Recent studies focusing on the degradation behaviour of additively manufactured Magnesium scaffolds disclosed additional intricacies when compared to conventionally manufactured Magnesium parts, as a notably larger surface area was exposed to the immersion medium and scaffold struts degraded non-uniformly. Moreover, chemical etching as post processing technique is applied to remove sintered powder particles from the surface, altering surface chemistry. In this study, cylindrical Magnesium specimens were manufactured by LPBF and surfaces were consecutively modified by phosphoric etching and machining. Degradation behaviour and biocompatibility were then investigated, revealing that etched samples exhibited the overall lowest degradation rates, but experienced large pit formation, while the reduction of surface roughness resulted in a delay of degradation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Titanium is one of the most commonly used materials for implants in trauma applications due to its low density, high corrosion resistance and biocompatibility. Nevertheless, there is still a need for improved surface modifications of Titanium, in order to change surface properties such as wettability, antibacterial properties or tissue attachment. In this study, different novel plasma electrolytic oxidation (PEO) modifications have been investigated for tendon adhesion to implants commonly used in hand surgery. Titanium samples with four different PEO modifications were prepared by varying the electrolyte composition and analyzed with regards to their surface properties. Unmodified titanium blanks and Dotize® coating served as controls. Samples were examined using scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), contact angle measuring system and analyzed for their biocompatibility and hemocompatibility (according to DIN ISO 10993-5 and 10,993-4). Finally, tendon adhesion of these specific surfaces were investigated by pull-off tests. Our findings show that surface thickness of PEO modifications was about 12-20 μm and had porous morphology. One modification demonstrated hydrophilic behavior accompanied by good biocompatibility without showing cytotoxic properties. Furthermore, no hemolytic effect and no significant influence on hemocompatibility were observed. Pull-off tests revealed a significant reduction of tendon adhesion by 64.3% (35.7% residual adhesion), compared to unmodified titanium (100%). In summary, the novel PEO-based ceramic-like porous modification for titanium surfaces might be considered a good candidate for orthopedic applications supporting a more efficient recovery., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Open-porous scaffolds of WE43 Mg alloy with a body-center cubic cell pattern were manufactured by laser powder bed fusion with different strut diameters. The geometry of the unit cells was adequately reproduced during additive manufacturing and the porosity within the struts was minimized. The microstructure of the scaffolds was modified by means of thermal solution and ageing heat treatments and was analysed in detail by means of X-ray microtomography, optical, scanning and transmission electron microscopy. Moreover, the corrosion rates and the mechanical properties of the scaffolds were measured as a function of the strut diameter and metallurgical condition. The microstructure of the as-printed scaffolds contained a mixture of Y-rich oxide particles and Rare Earth-rich intermetallic precipitates. The latter could be modified by heat treatments. The lowest corrosion rates of 2-3 mm/year were found in the as-printed and solution treated scaffolds and they could be reduced to ~0.1 mm/year by surface treatments using plasma electrolytic oxidation. The mechanical properties of the scaffolds improved with the strut diameter: the yield strength increased from 8 to 40 MPa and the elastic modulus improved from 0.2 to 0.8 GPa when the strut diameter increased from 275 μm to 800 μm. Nevertheless, the strength of the scaffolds without plasma electrolytic oxidation treatment decreased rapidly when immersed in simulated body fluid. In vitro bicompatibility tests showed surface treatments by plasma electrolytic oxidation were necessary to ensure cell proliferation in scaffolds with high surface-to-volume ratio., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Magnesium shows promising properties concerning its use in absorbable implant applications such as biodegradability, improved mechanical strength and plastic deformability. Following extensive research, the first fixation and compression screws composed of magnesium rare earth alloys were commercialised, notably in the field of orthopaedic surgery. Preclinical and clinical follow-up studies showed that the rapid degradation of unprotected metallic Magnesium surfaces and concomitant hydrogen gas bursts still raise concern regarding certain surgical indications and need to be further improved. In order to enlarge the scope of further applications, the development of future magnesium implants must aim at freedom of design and reduction of volume, hereby enabling higher functionalised implants, as e.g. plate systems or scaffold grafts for bone replacement therapy. In order to overcome the boundaries of conventional manufacturing methods such as turning or milling, the process of Laser Powder Bed Fusion (LPBF) for magnesium alloys was recently introduced. It enables the production of lattice structures, therefore allowing for reduction of implant material volume. Nevertheless, the concomitant increase of free surface of such magnesium scaffolds further stresses the aforementioned disadvantages of vast degradation and early loss of mechanical stability if not prevented by suitable postprocessing methods. Magnesium scaffold structures with different pore sizes were therefore manufactured by LPBF and consequently further modified either by thermal heat treatment or Plasma Electrolytic Oxidation (PEO). Implant performance was assessed by conducting degradation studies and mechanical testing. PEO modified scaffolds with small pore sizes exhibited improved long-term stability, while heat treated specimens showed impaired performance regarding degradation and mechanical stability. STATEMENT OF SIGNIFICANCE: Magnesium based scaffold structures offer wide possibilities for advanced functionalized bioabsorbable implants. By implementing lattice structures, big implant sizes and mechanically optimized implant geometries can be achieved enabling full bone replacement or large-scale plate systems, e.g. for orthopedic applications. As shape optimization and lattice structuring of such scaffolds consequently lead to enlarged surface, suitable design and postprocessing routines come into focus. The presented study addresses these new and relevant topics for the first time by evaluating geometry as well as heat and surface treatment options as input parameters for improved chemical and mechanical stability. The outcome of these variations is measured by degradation tests and mechanical analysis. Evaluating these methods, a significant contribution to the development of absorbable magnesium scaffolds is made. The findings can help to better understand the interdependence of high surface to volume ratio Magnesium implants and to deliver methods to incorporate such lattice structures into future large-scale implant applications manufactured from bioabsorbable Magnesium alloys., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Percutaneous transluminal coronary angioplasty and subsequent vascular scaffold implantation remains the prevalent invasive treatment of coronary heart disease. In-stent restenosis remained a problem with bare metal stents, until drug-eluting stents were introduced. The inhibition of the healing process by the antimitotic drug coating and the permanent metallic remnant can promote sub-acute and delayed stent thrombosis. Thus, the development of biodegradable stents emerged as a subject of research. Magnesium-based bioabsorbable devices can provide sufficient radial force in the acute phase of vessel-treatment and degrade thoroughly in aqueous environment, making them potential new candidates for vascular scaffold applications. Magnesium alloys tend to degrade very quickly due to their high electrochemical corrosion potential. Plasma Electrolytic Oxidation modification of magnesium alloys improves interface and degradadation properties and may therefore enhance the performance and suitability for vascular scaffold applications of these materials. Assuring the hemocompatibility and foremost assessing the thrombogenicity of new biomaterials prior to their use is essential in order to avoid adverse effects. The goal was to assess thrombocyte adhesion on coated Mg-RE and Mg-Zn-Ca alloys. Static experiments with human blood were carried out on the plasma-electrolytically treated or corresponding untreated Mg alloy in order to assess quantity and quality of thrombocyte adhesion via standardized SEM imaging. In a second step, a parallel plate flow chamber was designed in order to examine thrombocyte adhesion under dynamic flow conditions. During flow chamber experiments the test-materials were exposed to human thrombocyte concentrate and the number of adherent thrombocytes was assessed. The flow chamber was additionally perfused with human blood and thrombocyte adhesion was semiquantitatively and qualitatively assessed via SEM imaging and subsequent scoring. In conclusion, a new parallel plate flow chamber design simulating blood-circulation was successfully established, enabling the further assessment of platelet adhesion on bioabsorbable materials under dynamic flow conditions. Static and dynamic experiments showed, that plasma-electrolytically treated specimens showed low thrombocyte adhesion on both alloys, proposing their potential use in vascular scaffolds. The uncoated magnesium alloys showed rapid degradation along with gas formation due to the chemically active surface and therefore give concern regarding their safety and suitability for vascular applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Magnesium (Mg) is a promising biomaterial for degradable implant applications that has been extensively studied in vitro and in vivo in recent years. In this study, we developed a procedure that allows an optimized and uniform in vitro assessment of the cytocompatibility of Mg-based materials while respecting the standard protocol DIN EN ISO 10993-5:2009. The mouse fibroblast line L-929 was chosen as the preferred assay cell line and MEM supplemented with 10% FCS, penicillin/streptomycin and 4mM l-glutamine as the favored assay medium. The procedure consists of (1) an indirect assessment of effects of soluble Mg corrosion products in material extracts and (2) a direct assessment of the surface compatibility in terms of cell attachment and cytotoxicity originating from active corrosion processes. The indirect assessment allows the quantification of cell-proliferation (BrdU-assay), viability (XTT-assay) as well as cytotoxicity (LDH-assay) of the mouse fibroblasts incubated with material extracts. Direct assessment visualizes cells attached to the test materials by means of live-dead staining. The colorimetric assays and the visual evaluation complement each other and the combination of both provides an optimized and simple procedure for assessing the cytocompatibility of Mg-based biomaterials in vitro., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)