Challenges and Pitfalls of Research Designs Involving Magnesium-Based Biomaterials: An Overview.

Magnesium-based biomaterials hold remarkable promise for various clinical applications, offering advantages such as reduced stress-shielding and enhanced bone strengthening and vascular remodeling compared to traditional materials. However, ensuring the quality of preclinical research is crucial for the development of these implants. To achieve implant success, an understanding of the cellular responses post-implantation, proper model selection, and good study design are crucial. There are several challenges to reaching a safe and effective translation of laboratory findings into clinical practice. The utilization of Mg-based biomedical devices eliminates the need for biomaterial removal surgery post-healing and mitigates adverse effects associated with permanent biomaterial implantation. However, the high corrosion rate of Mg-based implants poses challenges such as unexpected degradation, structural failure, hydrogen evolution, alkalization, and cytotoxicity. The biocompatibility and degradability of materials based on magnesium have been studied by many researchers in vitro; however, evaluations addressing the impact of the material in vivo still need to be improved. Several animal models, including rats, rabbits, dogs, and pigs, have been explored to assess the potential of magnesium-based materials. Moreover, strategies such as alloying and coating have been identified to enhance the degradation rate of magnesium-based materials in vivo to transform these challenges into opportunities. This review aims to explore the utilization of Mg implants across various biomedical applications within cellular (in vitro) and animal (in vivo) models.

In Vivo Simulation of Magnesium Degradability Using a New Fluid Dynamic Bench Testing Approach.

The degradation rate of magnesium (Mg) alloys is a key parameter to develop Mg-based biomaterials and ensure in vivo-mechanical stability as well as to minimize hydrogen gas production, which otherwise can lead to adverse effects in clinical applications. However, in vitro and in vivo results of the same material often differ largely. In the present study, a dynamic test bench with several single bioreactor cells was constructed to measure the volume of hydrogen gas which evolves during magnesium degradation to indicate the degradation rate in vivo. Degradation medium comparable with human blood plasma was used to simulate body fluids. The media was pumped through the different bioreactor cells under a constant flow rate and 37 °C to simulate physiological conditions. A total of three different Mg groups were successively tested: Mg WE43, and two different WE43 plasma electrolytically oxidized (PEO) variants. The results were compared with other methods to detect magnesium degradation (pH, potentiodynamic polarization (PDP), cytocompatibility, SEM (scanning electron microscopy)). The non-ceramized specimens showed the highest degradation rates and vast standard deviations. In contrast, the two PEO samples demonstrated reduced degradation rates with diminished standard deviation. The pH values showed above-average constant levels between 7.4-7.7, likely due to the constant exchange of the fluids. SEM revealed severe cracks on the surface of WE43 after degradation, whereas the ceramized surfaces showed significantly decreased signs of corrosion. PDP results confirmed the improved corrosion resistance of both PEO samples. While WE43 showed slight toxicity in vitro, satisfactory cytocompatibility was achieved for the PEO test samples. In summary, the dynamic test bench constructed in this study enables reliable and simple measurement of Mg degradation to simulate the in vivo environment. Furthermore, PEO treatment of magnesium is a promising method to adjust magnesium degradation.

Improved In Vitro Test Procedure for Full Assessment of the Cytocompatibility of Degradable Magnesium Based on ISO 10993-5/-12.

Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nevertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continuous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristics were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and osteogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations.

Sustainable Bombyx mori's silk fibroin for biomedical applications as a molecular biotechnology challenge: A review.

Silk is a natural engineering material with a unique set of properties. The major constituent of silk is fibroin, a protein widely used in the biomedical field because of its mechanical strength, toughness and elasticity, as well as its biocompatibility and biodegradability. The domestication of silkworms allows large amounts of fibroin to be extracted inexpensively from silk cocoons. However, the industrial extraction process has drawbacks in terms of sustainability and the quality of the final medical product. The heterologous production of fibroin using recombinant DNA technology is a promising approach to address these issues, but the production of such recombinant proteins is challenging and further optimization is required due to the large size and repetitive structure of fibroin's DNA and amino acid sequence. In this review, we describe the structure-function relationship of fibroin, the current extraction process, and some insights into the sustainability of silk production for biomedical applications. We focus on recent advances in molecular biotechnology underpinning the production of recombinant fibroin, working toward a standardized, successful and sustainable process.

Bioabsorbable WE43 Mg alloy wires modified by continuous plasma-electrolytic oxidation for implant applications. Part I: Processing, microstructure and mechanical properties.

In our work, a novel processing strategy for the continuous fabrication and surface modification of wires from Magnesium alloy WE43 by means of plasma-electrolytic oxidation (PEO) is presented. In the first step, wires with a strong basal texture and small grain size (≈ 1 µm) were manufactured by combined cold drawing and in-line stress-relief heat treatment steps that optimized the mechanical properties (in terms of strength and ductility) by means of annealing. In a second step, and to the best of our knowledge for the first time ever, the wires were continuously surface-modified with a novel plasma electrolytic oxidation process, which was able to create a homogeneous porous oxide layer made of MgO and Mg3(PO4)2 on the wire surface. While the oxide layer slightly diminished the tensile properties, the strength of the surface-modified wires could be maintained close to 300 MPa with a strain-to-failure ≈ 8 %. Furthermore, the thickness of the oxide layer could be controlled by immersion time within the electrolytic bath and was adjusted to realize a thicknesses of ≈ 8 µm, which could be obtained in <20 s. Our experiments showed that the chemical composition, morphology and porosity of the oxide layer could be tailored by changing electrical parameters. The combined cold drawing and heat treatment process with additional continuous plasma electrolytic oxidation processing can be upscaled to produce a novel generation of bioabsorbable Mg wires with optimized mechanical, degradation and biological performance for use in biomedical applications.

Bioabsorbable WE43 Mg alloy wires modified by continuous plasma electrolytic oxidation for implant applications. Part II: Degradation and biological performance.

The corrosion, mechanical degradation and biological performance of cold-drawn WE43 Mg wires were analyzed as a function of thermo-mechanical processing and the presence of a protective oxide layer created by continuous plasma electrolytic oxidation (PEO). It was found that the corrosion properties of the non-surface-treated wire could be optimized by means of thermal treatment within certain limits, but the corrosion rate remained very high. Hence, strength and ductility of these wires vanished after 24 h of immersion in simulated body fluid at 37 °C and, as a result of that rather quick degradation, direct tests did not show any MC3T3-E1 preosteoblast cell attachment on the surface of the Mg wires. In contrast, surface modification of the annealed WE43 Mg wires by a continuous PEO process led to the formation of a homogeneous oxide layer of ≈8 µm and significantly improved the corrosion resistance and hence the biocompatibility of the WE43 Mg wires. It was found that a dense layer of Ca/P was formed at the early stages of degradation on top of the Mg(OH)2 layer and hindered the diffusion of the Cl- ions which dissolve Mg(OH)2 and accelerate the corrosion of Mg alloys. As a result, pitting corrosion was suppressed and the strength of the Mg wires was above 100 MPa after 96 h of immersion in simulated body fluid at 37 °C. Moreover, many cells were able to attach on the surface of the PEO surface-modified wires during cell culture testing. These results demonstrate the potential of thin Mg wires surface-modified by continuous PEO in terms of mechanical, degradation and biological performance for bioabsorbable wire-based devices.

An enhanced phenomenological model to predict surface-based localised corrosion of magnesium alloys for medical use.

This study developed an enhanced phenomenological model for the predictions of surface-based localised corrosion of magnesium alloys for use in medical applications. The modelling framework extended previous surface-based approaches by considering the role of ß-phase components throughout the material volume to better predict spatial and temporal aspects of surface-based corrosion in magnesium alloys. This enhanced surface-based corrosion model offers many advantages as it (i) captures multi-directional pitting, (ii) captures various pit morphologies, (iii) eliminates mesh sizing effects, (iv) reduces computational cost through custom time controls (v) offers control of pit sizing and (vi) produces corrosion rates that are independent of pitting parameter values. The model was fully implemented in three dimensions within the finite element framework and shows excellent potential to enable robust predictions of the long-term performance of magnesium-based implants undergoing corrosion.

Evolution from Bioinert to Bioresorbable: In Vivo Comparative Study of Additively Manufactured Metal Bone Scaffolds.

Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals - the most successful orthopedic material - have yet to yield satisfactory results. Conventional bio-inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non-bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L-PBF) technology. This in vivo study presents a comprehensive, side-by-side comparative analysis of the interactions between bone regeneration and additively manufactured bio-inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in-depth understanding of the metal scaffold-assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.

Layer-by-Layer Deposition of Regenerated Silk Fibroin─An Approach to the Surface Coating of Biomedical Implant Materials.

Biomaterials and coating techniques unlock major benefits for advanced medical therapies. Here, we explored layer-by-layer (LbL) deposition of silk fibroin (SF) by dip coating to deploy homogeneous films on different materials (titanium, magnesium, and polymers) frequently used for orthopedic and other bone-related implants. Titanium and magnesium specimens underwent preceding plasma electrolytic oxidation (PEO) to increase hydrophilicity. This was determined as surface properties were visualized by scanning electron microscopy and contact angle measurements as well as Fourier transform infrared spectroscopy (FTIR) analysis. Finally, biological in vitro evaluations of hemocompatibility, THP-1 cell culture, and TNF-α assays were conducted. A more hydrophilic surface could be achieved using the PEO surface, and the contact angle for magnesium and titanium showed a reduction from 73 to 18° and from 58 to 17°, respectively. Coating with SF proved successful on all three surfaces, and coating thicknesses of up to 5.14 µm (±SD 0.22 µm) were achieved. Using FTIR analysis, it was shown that the insolubility of the material was achieved by post-treatment with water vapor annealing, although the random coil peak (1640-1649 cm-1) and the α-helix peak (at 1650 cm-1) were still evident. SF did not change hemocompatibility, regardless of the substrate, whereas the PEO-coated materials showed improved hemocompatibility. THP-1 cell culture showed that cells adhered excellently to all of the tested material surfaces. Interestingly, SF coatings induced a significantly higher amount of TNF-α for all materials, indicating an inflammatory response, which plays an important role in a variety of physiological processes, including osteogenesis. LbL coatings of SF are shown to be promising candidates to modulate the body's immune response to implants manufactured from titanium, magnesium, and polymers. They may therefore facilitate future applications for bioactive implant coatings. However, further in vivo studies are needed to confirm the proposed effects on osteogenesis in a physiological environment.

Long-term in vivo observations show biocompatibility and performance of ZX00 magnesium screws surface-modified by plasma-electrolytic oxidation in Göttingen miniature pigs.

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.

Development and validation of a parametric human mandible model to determine internal stresses for the future design optimization of maxillofacial implants.

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.

Antibacterial properties of functionalized silk fibroin and sericin membranes for wound healing applications in oral and maxillofacial surgery.

Oral wounds are among the most troublesome injuries which easily affect the patients' quality of life. To date, the development of functional antibacterial dressings for oral wound healing remains a challenge. In this regard, we investigated antibacterial silk protein-based membranes for the application as wound dressings in oral and maxillofacial surgery. The present study includes five variants of casted membranes, i.e., i) membranes-silver nanoparticles (CM-Ag), ii) membranes-gentamicin (CM-G), iii) membranes-control (without functionalization) (CM-C), iv) membranes-silk sericin control (CM-SSC), and v) membranes-silk fibroin/silk sericin (CM-SF/SS), and three variants of nonwovens, i.e., i) silver nanoparticles (NW-Ag), ii) gentamicin (NW-G), iii) control (without functionalization) (NW-C). The surface structure of the samples was visualized with scanning electron microscopy. In addition, antibacterial testing was accomplished using agar diffusion assay, colony forming unit (CFU) analysis, and qrt-PCR. Following antibacterial assays, biocompatibility was evaluated by cell proliferation assay (XTT), cytotoxicity assay (LDH), and live-dead assay on L929 mouse fibroblasts. Findings indicated significantly lower bacterial colony growth and DNA counts for CM-Ag with a reduction of bacterial counts by 3log levels (99.9% reduction) in CFU and qrt-PCR assay compared to untreated control membranes (CM-C and CM-SSC) and membranes functionalized with gentamicin (CM-G and NW-G) (p < 0.001). Similarly, NW-G yielded significantly lower DNA and colony growth counts compared to NW-Ag and NW-C (p < 0.001). In conclusion, CM-Ag represented 1log level better antibacterial activity compared to NW-G, whereas NW-G showed better cytocompatibility for L929 cells. As data suggest, these two membranes have the potential of application in the field of bacteria-free oral wound healing. However, provided that loading strategy and cytocompatibility are adjusted according to the antibacterial agents' characteristic and fabrication technique of the membranes.

Strength, corrosion resistance and cellular response of interfaces in bioresorbable poly-lactic acid/Mg fiber composites for orthopedic applications.

The shear strength and the corrosion resistance of the fiber/matrix interface after immersion in simulated body fluid was studied in poly-lactic acid/Mg fiber composites. The shear strength of the interface was measured by means of push-out tests in thin slices of the composite perpendicular to the fibers. It was found that the interface strength dropped from 15.2 ± 1.4 MPa to 7.8 ± 3.7 MPa after the composite was immersed in simulated body fluid for 148 h. The reduction of the interface strength was associated to the fast corrosion of the fibers as water diffused to the interface through the polymer. The expansion of the fibers due to the formation of corrosion products was enough to promote radial cracks in the polymer matrix which facilitate the ingress of water and the development of corrosion pitting in the fibers. Moreover, cell culture testing on the material showed that early degradation of the Mg fibers affected the proliferation of pre-osteoblasts near the Mg fibers due to the local changes in the environment produced by the fiber corrosion. Thus, surface modification of Mg fibers to delay degradation seems to be a critical point for further development of Mg/PLA composites for biomedical applications.

Microstructure, mechanical properties, corrosion resistance and cytocompatibility of WE43 Mg alloy scaffolds fabricated by laser powder bed fusion for biomedical applications.

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.

Towards a flexible electrochemical biosensor fabricated from biocompatible Bombyx mori silk.

In modern days, there is an increasing relevance of and demand for flexible and biocompatible sensors for in-vivo and epidermal applications. One promising strategy is the implementation of biological (natural) polymers, which offer new opportunities for flexible biosensor devices due to their high biocompatibility and adjustable biodegradability. As a proof-of-concept experiment, a biosensor was fabricated by combining thin- (for Pt working- and counter electrode) and thick-film (for Ag/AgCl quasi-reference electrode) technologies: The biosensor consists of a fully bio-based and biodegradable fibroin substrate derived from silk fibroin of the silkworm Bombyx mori combined with immobilized enzyme glucose oxidase. The flexible glucose biosensor is encapsulated by a biocompatible silicon rubber which is certificated for a safe use onto human skin. Characterization of the sensor set-up is exemplarily demonstrated by glucose measurements in buffer and Ringer's solution, while the stability of the quasi-reference electrode has been investigated versus a commercial Ag/AgCl reference electrode. Repeated bending studies validated the mechanical properties of the electrode structures. The cross-sensitivity of the biosensor against ascorbic acid, noradrenaline and adrenaline was investigated, too. Additionally, biocompatibility and degradation tests of the silk fibroin with and without thin-film platinum electrodes were carried out.

A novel titanium implant surface modification by plasma electrolytic oxidation (PEO) preventing tendon adhesion.

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.

Improved in vivo osseointegration and degradation behavior of PEO surface-modified WE43 magnesium plates and screws after 6 and 12 months.

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 mm2; WE43-PEO: 6,9 ± 5.2 mm2; 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.

Influence of surface condition on the degradation behaviour and biocompatibility of additively manufactured WE43.

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.

Influence of design and postprocessing parameters on the degradation behavior and mechanical properties of additively manufactured magnesium scaffolds.

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.

Surface Characteristics of Esthetic Nickel⁻Titanium and Beta-Titanium Orthodontic Archwires Produced by Plasma Electrolytic Oxidation (PEO)-Primary Results.

BACKGROUND/AIM: There is continuing interest in engineering esthetic labial archwires. The aim of this study was to coat nickel-titanium (NiTi) and beta-titanium (ß-Ti), also known as titanium molybdenum (TMA), archwires by plasma electrolytic oxidation (PEO) and to analyze the characteristics of the PEO-surfaces. MATERIALS AND METHODS: PEO-coatings were generated on 0.014-inch NiTi and 0.19 × 0.25-inch ß-Ti archwires. The surfaces were analyzed by scanning electron microscopy and stereomicroscopy. Cytocompatibility testing was performed with ceramized and untreated samples according to EN ISO 10993-5 in XTT-, BrdU- and LDH-assays. The direct cell impact was analyzed using LIVE-/DEAD-staining. In addition, the archwires were inserted in an orthodontic model and photographs were taken before and after insertion. RESULTS: The PEO coatings were 15 to 20 µm thick with a whitish appearance. The cytocompatibility analysis revealed good cytocompatibility results for both ceramized NiTi and ß-Ti archwires. In the direct cell tests, the ceramized samples showed improved compatibility as compared to those of uncoated samples. However, bending of the archwires resulted in loss of the PEO-surfaces. Nevertheless, it was possible to insert the ß-Ti PEO-coated archwire in an orthodontic model without loss of the PEO-ceramic. CONCLUSION: PEO is a promising technique for the generation of esthetic orthodontic archwires. Since the PEO-coating does not resist bending, its clinical use seems to be limited so far to orthodontic techniques using straight or pre-bent archwires.