Elsevier

Acta Biomaterialia

Volume 84, 15 January 2019, Pages 453-467
Acta Biomaterialia

Full length article
Biomimetic porous Mg with tunable mechanical properties and biodegradation rates for bone regeneration

https://doi.org/10.1016/j.actbio.2018.11.045Get rights and content

Abstract

The medical applications of porous Mg scaffolds are limited owing to its rapid corrosion, which dramatically decreases the mechanical strength of the scaffold. Mimicking the bone structure and composition can improve the mechanical and biological properties of porous Mg scaffolds. The Mg structure can also be coated with HA by an aqueous precipitation coating method to enhance both the corrosion resistance and the biocompatibility. However, due to the brittleness of HA coating layer, cracks tend to form in the HA coating layer, which may influence the corrosion and biological functionality of the scaffold. Consequently, in this study, hybrid poly(ether imide) (PEI)–SiO2 layers were applied to the HA-coated biomimetic porous Mg to impart the structure with the high corrosion resistance associated with PEI and excellent bioactivity with SiO2. The porosity of the Mg was controlled by adjusting the concentration of the sodium chloride (NaCl) particles used in the fabrication via the space-holder method. The mechanical measurements showed that the compressive strength and stiffness of the biomimetic porous Mg increased as the portion of the dense region increased. In addition, following results show that HA/(PEI–SiO2) hybrid-coated biomimetic Mg is a promising biodegradable scaffold for orthopedic applications. In-vitro testing revealed that the proposed hybrid coating reduced the degradation rate and facilitated osteoblast spreading compared to HA- and HA/PEI-coating scaffolds. Moreover, in-vivo testing with a rabbit femoropatellar groove model showed improved tissue formation, reduced corrosion and degradation, and improved bone formation on the scaffold.

Statement of Significance

Porous Mg is a promising biodegradable scaffold for orthopedic applications. However, there are limitations in applying porous Mg for an orthopedic biomaterial due to its poor mechanical properties and susceptibility to rapid corrosion. Here, we strategically designed the structure and coating layer of porous Mg to overcome these limitations. First, porous Mg was fabricated by mimicking the bone structure which has a combined structure of dense and porous regions, thus resulting in an enhancement of mechanical properties. Furthermore, the biomimetic porous Mg was coated with HA/(PEI-SiO2) hybrid layer to improve both corrosion resistance and biocompatibility. As the final outcome, with tunable mechanical and biodegradable properties, HA/(PEI-SiO2)-coated biomimetic porous Mg could be a promising candidate material for load-bearing orthopedic applications.

Introduction

Magnesium (Mg) is a potential candidate for orthopedic implants because Mg and its alloys exhibit good biocompatibility and have suitable mechanical properties that are similar to those of bone [1], [2]. Moreover, unlike the metals, such as titanium, stainless steel, and cobalt-chromium, that are used for conventional implants, Mg is biodegradable under physiological conditions. Therefore, an additional surgery to remove the implant from the body after the damaged bone tissue has healed fully becomes unnecessary [1], [3]. Furthermore, porous Mg scaffolds facilitate bone ingrowth into the pores, which in turn facilitates firmer implant fixation at the initial state of implantation and nutrient transport for faster healing, thereby making it a promising material for orthopedic applications [4], [5], [6].

However, the medical applications of porous Mg scaffolds are limited due to their rapid corrosion, which dramatically decreases the mechanical strength of the scaffold and generates excessive hydrogen gas bubbles and hydroxide ions that prevent the surrounding tissues from healing [1], [7], [8]. Various methods have been proposed to improve the corrosion resistance of Mg, such as surface treatments [9], [10], alloying [11], or grain refinement [12]. Surface treatment is relatively a simple but an effective way to prevent the corrosion of an Mg scaffold without impacting its inherent properties. These surface treatments include hydroxyapatite (HA) coating by an aqueous precipitation method, which is an efficient way to coat complex shapes of porous Mg and attain high corrosion resistance and good biocompatibility with bone tissue [10], [13], [14].

For load-bearing orthopedic applications, Mg scaffolds require high strength to support the loads applied to the scaffold and a low degradation rate such that they will degrade once the damaged bone tissue has recovered [15]. The mechanical properties of HA-coated porous Mg with varying porosities (50–70%) were characterized in a previous study [16]. The results showed that HA-coated porous Mg is still not suitable for use in load-bearing orthopedic applications due to its insufficient strength, likely due to its porous structure. This limits its potential for use as a replacement material for cancellous bone [16], [17], [18], [19]. Moreover, due to the inherent brittleness of HA, cracks often form on the HA coating layer, which may allow body fluids to penetrate through the cracks and reach the Mg structure [20], [21], [22]. Therefore, for load-bearing orthopedic applications, there is a need for new coatings for structurally designed porous Mg that will both retain its excellent mechanical strength and corrode at a controlled rate.

One approach to improving the mechanical properties of porous Mg scaffolds is to mimic the structure of bone [23], [24]. Bone comprises a combination of dense and interconnected porous regions, providing it with high strength [25]. Thus, we hypothesize that Mg scaffolds with both dense and porous structures will have high strength while maintaining the biological advantages of the porous structure. In this study, we fabricated an Mg scaffold mimicking the structure of bone using spark plasma sintering (SPS) and the space-holder method. SPS is a noteworthy method used to sinter reactive metal such as Mg, which reacts with oxygen or water easily.

Furthermore, a hybrid polymeric coating was applied over the HA coating on the porous Mg scaffold to slowdown the degradation and suppress crack formation in the HA layer. Poly(ether imide) (PEI) polymer is a good candidate for this coating because of its excellent corrosion resistance, good flexibility, and biocompatibility [26], [27], [28], [29]. However, PEI also has low bioactivity and, as a result, is less osteoconductive than other bioceramic coatings like HA [30], [31]. To improve the osteoconductivity of PEI, bioactive nanoparticles, such as silica (SiO2) nanoparticles synthesized by the sol–gel method, can be uniformly distributed in the PEI matrix to enhance the bioactivity of the coating [32], [33], [34]. The addition of SiO2 to PEI improved its biocompatibility and bioactivity because the hydroxyl functional groups in SiO2 should make the coating more hydrophilic and facilitate chemical bonds between the coating and the cells, and Si ions released upon degradation will stimulate growth in the surrounding bone tissue [34].

Herein, biomimetic porous Mg scaffolds mimicking the structure of bone were fabricated by SPS of an Mg/NaCl composite followed by dissolving NaCl to form a porous structure. The obtained biomimetic porous Mg was then coated with HA followed by a PEI–SiO2 hybrid layer to improve the corrosion resistance and bioactivity of the scaffold. The structural morphology of biomimetic porous Mg was examined by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and micro-computed tomography (μ-CT). The morphologies, chemical structures, and hydrophilic properties of the HA/(PEI–SiO2) hybrid coating layers containing varying amounts of SiO2 were evaluated by SEM and wetting-angle tests. Moreover, the mechanical behaviors of the scaffolds were evaluated by mechanical compression tests. In addition, the corrosion behavior of HA/(PEI–SiO2)-coated porous Mg was evaluated by a hydrogen gas evolution test and its bioactivity was observed through in-vitro cell tests and in-vivo animal tests.

Section snippets

Fabrication of conventional and biomimetic porous Mg

The fabrication process is shown in Fig. 1(a). NaCl particles (larger than 80 mesh, Sigma Aldrich, USA) were added as the pore generator in a volume fraction of 70% to Mg powder (between 100 and 200 mesh, 99.6%, Alfa Aesar, USA) with a small amount of ethanol as a binder. The mixed powders were then pressed with a force of 20 MPa in a carbon die (12 mm inner diameter). Spark plasma sintering (SPS, Well Tech, Korea) was performed at 585 °C for 2 h under vacuum. After the sintering process, the

Physical structure of the biomimetic porous Mg

The porosity of the porous region in porous Mg was designed to be 70% to closely match that in a trabecular bone as shown in Fig. 2. The calculated porosities of the trabecular bone harvested from the femoropatellar joint defects were approximately 70% as measured using μ-CT. Fig. 3 shows the representative optical images of the conventional porous Mg and biomimetic porous Mg with different ratios of dense and porous areas by controlling the volume of the Mg/NaCl compact before sintering. Thus,

Fabrication process

Most studies of porous Mg for biomedical applications focus on the influence of the fabrication method on the mechanical strength and porosity of the scaffold [16], [19], [38], [44], [45], [46]. However, in this study, the optimization was conducted by mimicking the natural structure of bone to realize biomimetic mechanical behavior for load-bearing applications. First, biomimetic porous Mg was fabricated via the space-holder method using NaCl followed by the SPS process. By this approach, the

Conclusion

In this study, we successfully fabricated the porous Mg mimicking the structure of natural bone by SPS with an Mg powder blended with NaCl acting as a sacrificial pore generator. The structure of the obtained porous Mg was similar to that of bone, including high interconnectivity and mechanical properties sufficient for load-bearing applications; these features make this porous Mg an excellent candidate material for orthopedic applications. Furthermore, the biocorrosion of the porous Mg was

Acknowledgements

This research was supported by Basic Science Research Program (No. 2018R1C1B6001003) through the National Research Foundation of Korea and Technology Innovation Program (10037915, WPM Biomedical Materials–Implant Materials) funded by the Ministry of Education and the Ministry of Trade, Industry & Energy.

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