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Bioabsorbable Mg wire-reinforced poly-lactic acid (PLA) matrix composites are potential candidate for load-bearing orthopedic implants offering tailorable mechanical and degradation properties by stacking sequence, volume fraction and surface modification of Mg wires. In this study, we investigated the cytocompatibility, cell-material interaction, and bone differentiation behavior of MC3T3-E1 pre-osteoblast cells for medical-grade PLA, Mg/PLA, and PEO-Mg/PLA (having PEO surface modification on Mg wires) composites. MTT and live/dead assay showed excellent biocompatibility of both composites while cell-material interaction analysis revealed that cells were able to adhere and proliferate on the surface of composites. Cells on the longitudinal surface of composites showed a high and uniform cell density while those on transversal surfaces initially avoided Mg regions but later migrated back after the formation of the passivation layer. Bone differentiation tests showed that cells in extracts of PLA and composites were able to initiate the differentiation process as osteogenesis-related gene expressions, alkaline phosphatase protein quantity, and calcium mineralization increased after 7 and 14 days of culture. Interestingly, the bone differentiation response of PEO-Mg/PLA composite was found to be similar to medical-grade PLA, proving its superiority over Mg/PLA composite., (© 2024 The Author(s). Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Cardiovascular stenting is the most widely used therapy to treat coronary artery disease caused by partial or total obstruction of the artery due to atherosclerotic plaque formation, with potentially fatal effects. There are different types of stents: bare metal stents, drug-eluting stents, bioabsorbable stents and dual therapy stents. However, they can lead to long-term complications, such as in-stent restenosis and late thrombosis. To reduce these adverse effects, research has focused on biodegradable metallic stents, since they retain the mechanical properties necessary to contain the injured artery while it is being repaired and, once their function has been fulfilled, the stent degrades without altering the system or compromising the patient's health. In this work we have evaluated the biological response of the degradation products of a bare Mg based biomaterial surface-modified by the plasma electrolytic oxidation (PEO) method on vascular tissue cells, hemocompatibility and inflammatory response. The results obtained are compatible with a biosafe material for future use as a cardiovascular implant, but it is necessary to continue with in vivo and mechanical properties tests to ensure and guarantee its use. SIGNIFICANCE STATEMENT: The development of fully bioresorbable stents is a promising alternative for the management of coronary artery disease without causing long-term problems at the implantation site. In this work, the hematological and immunological biocompatibility of bare Mg modified superficially by plasma electrolytic oxidation (PEO-Mg) was evaluated by in vitro and ex vivo assays. PEO-Mg was found to be compatible with blood and immune components surrounding the implantation site with no signs of toxicity to endothelial cells, macrophages, and arterial tissue. In addition, degradation products of PEO-Mg are eliminated by phagocytosis. However, an in-depth study of the physical and mechanical properties and in vivo biocompatibility must be carried out for its future use as a biomedical implant., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest Kopp is employed by Meotec GmbH. Presented magnesium wires are in development and commercially not available. The authors declare no conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Magnesium alloys are being studied for use in temporary orthopedic implants because of their mechanical properties, which are similar to those of human bone, and their good biocompatibility. However, their application is limited due to their rapid degradation, and early loss of their mechanical properties, decreasing the stability of the implant and its proper synchronization with tissue regeneration. In this regard, various surface coatings have been used to improve their biological, physico-chemical and biodegradation properties. Currently, one of the most explored strategies is using smart coatings because of their self-healing properties that can slow down the corrosion process of Mg and its alloys. Ceria-based materials show promise as coatings for these alloys. Their unique redox capacity not only provides Mg alloys with good self-healing properties but also interesting biological properties, which are described in this paper. Despite this, some problems and challenges related to the biocompatibility and application of these materials in coatings remain unsolved. In this article, a critical review is presented summarizing the most representative literature on ceria-based coatings on Mg alloys for their potential use as biomaterials. The results show that ceria is a versatile material that may be used in industrial and biomedical applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Magnesium-based nanoparticles have shown promise in regenerative therapies in orthopedics and the cardiovascular system. Here, we set out to assess the influence of differently functionalized Mg nanoparticles on the cellular players of wound healing, the first step in the process of tissue regeneration. First, we thoroughly addressed the physicochemical characteristics of magnesium hydroxide nanoparticles, which exhibited low colloidal stability and strong aggregation in cell culture media. To address this matter, magnesium hydroxide nanoparticles underwent surface functionalization by 3-aminopropyltriethoxysilane (APTES), resulting in excellent dispersible properties in ethanol and improved colloidal stability in physiological media. The latter was determined as a concentration- and time-dependent phenomenon. There were no significant effects on THP-1 macrophage viability up to 1.500 μg/mL APTES-coated magnesium hydroxide nanoparticles. Accordingly, increased media pH and Mg 2+ concentration, the nanoparticles dissociation products, had no adverse effects on their viability and morphology. HDF, ASCs, and PK84 exhibited the highest, and HUVECs, HPMECs, and THP-1 cells the lowest resistance toward nanoparticle toxic effects. In conclusion, the indicated high magnesium hydroxide nanoparticles biocompatibility suggests them a potential drug delivery vehicle for treating diseases like fibrosis or cancer. If delivered in a targeted manner, cytotoxic nanoparticles could be considered a potential localized and specific prevention strategy for treating highly prevalent diseases like fibrosis or cancer. Looking toward the possible clinical applications, accurate interpretation of in vitro cellular responses is the keystone for the relevant prediction of subsequent in vivo biological effects., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

One of the most common magnesium (Mg) applications in the biomedical field is in cardiovascular stents. Although Mg is an essential element for homeostasis, Mg is highly reactive, and locally high Mg concentrations can have toxic effects on the surrounding tissue. One strategy to circumvent the Mg toxicity is using coatings or surface modifications that prevent the leaching of excessive Mg ions. In the current study, commercially pure magnesium (c.p Mg) was modified through plasma electrolytic oxidation (PEO) to produce a protective coating primarily composed of Mg oxide (MgO) and Mg hydroxide (Mg(OH) 2 ), which limits leaching of free Mg ions from the base material. As we intend to use this material to produce vascular stents, a biological evaluation of its performance is warranted. Primary human umbilical vein endothelial cells (HUVECs) and smooth muscle cells (SMCs) were the study object. The leaching of free Mg ions from the oxidized materials was investigated, as was its effect on local pH changes. We also investigated the influence of corrosion products, the effects of elevated free Mg concentrations and pH on the cellular behavior on the integrity of monolayers of HUVECs was studied in a static and dynamic model. Results showed that the harmful effect of Mg on cells due to changes in pH and a high concentration of Mg ions could decrease with the influence of flow diffusing corrosion products such as MgO, Mg(OH) 2 , and H 2 among the system. Independently, Mg concentration and pH affected the cell activity of SMCs and HUVECs. Finally, to investigate the influence of leachables on vasomotor function, we exposed porcine aortic rings to PEO-modified Mg stents and assessed endothelial-dependent relaxation. Pure Mg reduced vasorelaxation from 100% in control samples to 30%. Oppositely, PEO-modified Mg did not affect the vasomotor function. Overall, we conclude from this study that the use of PEO coatings reduces the degradation rate of the material reducing the Mg release resulting in better cell viability and vessel function compared to the bare material., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Magnesium and its alloys have been recently used in biomedical applications such as orthopedic implants, whereas the weak corrosion resistance undermines their clinical efficacy. Herein, to address this critical challenge, the preparation of hierarchically structured hydroxyapatite-based coatings was proposed. Compact coatings were fabricated on a Mg alloy through a facile two-step method of chemical deposition of brushite precursor and subsequent hydrothermal conversion. A series of HA-based coatings were obtained with kinetic conversion process with formation mechanism revealed. The hydroxyapatite coating demonstrated the greatest corrosion resistance for Mg in electrochemical and long-term immersion tests, especially against pitting corrosion, attributable to its compact structure, alkaline degradation environment and self-induced growth capacity. The in vitro cytocompatibility and osteoinductivity were dictated. Additionally, anti-corrosion mechanisms were compared among different coating compositions and structures, along with their correlation with cellular response. Our study brings hints for a tailored surface design for resorbable biomedical device applications., (Copyright © 2020. Published by Elsevier B.V.)

Nanotubular structures were produced on a commercially pure titanium surface by anodization in an aqueous electrolyte that contained carboxymethyl cellulose and sodium fluoride. The internal diameters obtained were about 100, 48, and 9.5 nm, respectively. Several heat treatments at 200, 350, and 600°C were made to produce nanotubes with different titanium dioxide polymorphs (anatase, rutile). All tested surfaces were superhydrophilic, this behavior was maintained after at least 30 days, regardless of the heat treatment. Although in previous works the nanotube features effect on the bacteria behavior had been studied; this item still unclear. For the best of our knowledge, the effect of small internal diameters (about 10 nm) with and without heat treatment and with and without ultraviolet (UV) irradiation on the bacteria strains comportment has not been reported. From our results, both the internal diameter and the postanodized treatments have an effect on the bacteria strains comportment. All nanotubular coatings UV treated and heat treated at 350 and 600°C; despite they have different inner diameters, inhibit the bacteria growth of both Staphylococcus aureus and Pseudomonas aeruginosa strains. The nanotubular coatings obtained at 20 V and heat treated at 350°C produced the lower bacteria adhesion against both strains evaluated., (© 2020 Wiley Periodicals, Inc.)

Despite the well-known advantages of the titanium-based implant systems, they still lack an optimal balance between biofunctionality and mechanical strength, especially regarding the modulation of cellular response and a desired implant osseointegration. In this work, we fabricated a nanocomposite based on porous commercially pure grade 4 titanium (c.p. Ti) reinforced with carbon nanotubes (CNT) at 5% and 10% w/w, with the aim of obtaining a nanocomposite with lower stiffness compared to traditional titanium-based implants and with the mechanical strength and bioactivity owed by the CNT. Results obtained by scanning electron microscopy, X-ray photoelectron spectroscopy, and atomic force microscopy characterization showed that the CNT dispersed and incorporated into the porous c.p. Ti matrix. Interestingly, CNT were associated with a higher twining within neighbor Ti grains, which was indeed consistent with an increased in nano-hardness. Biological evaluation by MTT and Comet assay revealed that the nanocomposites did not induce genotoxicity and cytotoxicity on two different cells lines despite the presence of nickel at the surface. Accordingly, a purification step would be required before these CNT can be used for biomedical applications. Our results indicate that incorporation of CNT into porous c.p. Ti is a promising avenue to achieve an adequate balance between biofunctionality and mechanical strength in Ti-based scaffolds for tissue replacement. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 719-731, 2019., (© 2018 Wiley Periodicals, Inc.)

Surgical clipping and endovascular coiling are well recognized as conventional treatments of Penetrating Brain Injury aneurysms. These clinical approaches show partial success, but often result in thrombus formation and the rupture of aneurysm near arterial walls. The authors address these challenging brain traumas with a unique combination of a highly biocompatible biopolymer hydrogel rendered magnetic in a flexible and resilient membrane coating integrated to a scaffold stent platform at the aneurysm neck orifice, which enhances the revascularization modality. This work focuses on the in situ diagnosis of nano-mechanical behavior of bacterial nanocellulose (BNC) membranes in an aqueous environment used as tissue reconstruction substrates for cerebral aneurysmal neck defects. Nano-mechanical evaluation, performed using instrumented nano-indentation, shows with very low normal loads between 0.01 to 0.5 mN, in the presence of deionized water. Mechanical testing and characterization reveals that the nano-scale response of BNC behaves similar to blood vessel walls with a very low Young´s modulus, E (0.0025 to 0.04 GPa), and an evident creep effect (26.01 ± 3.85 nm s -1 ). These results confirm a novel multi-functional membrane using BNC and rendered magnetic with local adhesion of iron-oxide magnetic nanoparticles., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nanotubular structures were generated on the surface of titanium c.p. by anodization technique in an aqueous solution of acetic acid (14% v/v) with different sources of fluoride ion (HF, NaF, NH 4 F). The aim of using these three different compounds is to study the effect of the counterion (H + , Na + and NH4+) on the morphology, wettability and surface free energy of the modified surface. Nanotubes were generated at 10 and 15 V for each anodizing solution. To further improve surface characteristics, the samples were heat-treated at 600°C for 4 h and at 560°C for 3 h. SEM images revealed the formation of nanotubes in all anodizing conditions, while their diameter increased proportionally to the electric potential. X-ray diffraction and micro-Raman spectroscopy results showed the presence of both anatase and rutile phases, with a higher content of rutile in the coatings obtained using NH 4 F and an applied potential of 10 V. The heat-treatment significantly increased the wettability of the anodic coatings, especially for the coating obtained at 15 V with HF, which showed values < 7 degrees of contact angle. Besides, the nanotubes show a decrease in diameter due to the heat treatment, except for the nanotubes formed in NH 4 F. Depending on their surface properties (e.g. low contact angle and high surface free energy), these coatings potentially have great potential in biomedical applications, sensors devices, and catalytic applications among others. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1341-1354, 2018., (© 2018 Wiley Periodicals, Inc.)

Surface characteristics can mediate biological interaction improving or affecting the tissue integration after implantation of a biomaterial. Features such as topography, wettability, surface energy and chemistry can be key determinants for interactions between cells and materials. Plasma electrolytic oxidation (PEO) is a technique used to control this kind of parameters by the addition of chemical species and the production of different morphologies on the surfaces of titanium and its alloys. With the purpose to improve the biological response, surfaces of c.p titanium and Ti6Al4V were modified by using PEO. Different electrolytes, voltages, current densities and anodizing times were tested in order to obtain surfaces with different characteristics. The obtained materials were characterized by different techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM) and glow discharge optical emission spectroscopy (GDOES). Wettability of the obtained surfaces were measured and the corresponding surface energies were calculated. Superhydrophilic surfaces with contact angles of about 0 degrees were obtained without any other treatment but PEO and this condition in some cases remains stable after several weeks of anodizing; crystal phase composition (anatase-rutile) of the anodic surface appears to be critical for obtaining this property. Finally, in order to verify the biological effect of these surfaces, osteoblast were seeded on the samples. It was found that cell behavior improves as SFE (surface free energy) and coating porosity increases whereas it is affected negatively by roughness. Techniques for surface modification allow changes in the coatings such as surface energy, roughness and porosity. As a consequence of this, biological response can be altered. In this paper, surfaces of c.p Ti and Ti6Al4V were modified by using plasma electrolytic oxidation (PEO) in order to accelerate the cell adhesion process.

In this study, bacterial nanocellulose (BNC) produced by the bacteria Gluconacetobacter xylinus is synthesized and impregnated in situ with iron oxide nanoparticles (IONP) (Fe3O4) to yield a magnetic bacterial nanocellulose (MBNC). The synthesis of MBNC is a precise and specifically designed multi-step process. Briefly, bacterial nanocellulose (BNC) pellicles are formed from preserved G. xylinus strain according to our experimental requirements of size and morphology. A solution of iron(III) chloride hexahydrate (FeCl3·6H2O) and iron(II) chloride tetrahydrate (FeCl2·4H2O) with a 2:1 molar ratio is prepared and diluted in deoxygenated high purity water. A BNC pellicle is then introduced in the vessel with the reactants. This mixture is stirred and heated at 80 °C in a silicon oil bath and ammonium hydroxide (14%) is then added by dropping to precipitate the ferrous ions into the BNC mesh. This last step allows forming in situ magnetite nanoparticles (Fe3O4) inside the bacterial nanocellulose mesh to confer magnetic properties to BNC pellicle. A toxicological assay was used to evaluate the biocompatibility of the BNC-IONP pellicle. Polyethylene glycol (PEG) was used to cover the IONPs in order to improve their biocompatibility. Scanning electron microscopy (SEM) images showed that the IONP were located preferentially in the fibril interlacing spaces of the BNC matrix, but some of them were also found along the BNC ribbons. Magnetic force microscope measurements performed on the MBNC detected the presence magnetic domains with high and weak intensity magnetic field, confirming the magnetic nature of the MBNC pellicle. Young's modulus values obtained in this work are also in a reasonable agreement with those reported for several blood vessels in previous studies.

Titanium (Ti) is a material frequently used in orthopedic applications, due to its good mechanical properties and high corrosion resistance. However, formation of a non-adherent fibrous tissue between material and bone drastically could affect the osseointegration process and, therefore, the mechanical stability of the implant. Modifications of topography and configuration of the tissue/material interface is one of the mechanisms to improve that process by manipulating parameters such as morphology and roughness. There are different techniques that can be used to modify the titanium surface; plasma electrolytic oxidation (PEO) is one of those alternatives, which consists of obtaining porous anodic coatings by controlling parameters such as voltage, current, anodizing solution and time of the reaction. From all of the above factors, and based on previous studies that demonstrated that bone cells sense substrates features to grow new tissue, in this work commercially pure Ti (c.p Ti) and Ti6Al4V alloy samples were modified at their surface by PEO in different anodizing solutions composed of H2SO4 and H3PO4 mixtures. Treated surfaces were characterized and used as platforms to grow osteoblasts; subsequently, cell behavior parameters like adhesion, proliferation and differentiation were also studied. Although the results showed no significant differences in proliferation, differentiation and cell biological activity, overall results showed an important influence of topography of the modified surfaces compared with polished untreated surfaces. Finally, this study offers an alternative protocol to modify surfaces of Ti and their alloys in a controlled and reproducible way in which biocompatibility of the material is not compromised and osseointegration would be improved.