Full length articleBiomimetic porous Mg with tunable mechanical properties and biodegradation rates for bone regeneration
Graphical abstract
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.
References (85)
- et al.
Magnesium and its alloys as orthopedic biomaterials: a review
Biomaterials
(2006) - et al.
In vitro studies of biomedical magnesium alloys in a simulated physiological environment: a review
Acta Biomaterialia
(2011) - et al.
Biomedical coatings on magnesium alloys–a review
Acta Biomaterialia
(2012) - et al.
Biomaterials in co-culture systems: towards optimizing tissue integration and cell signaling within scaffolds
Biomaterials
(2014) - et al.
Porous chitosan scaffolds with surface micropatterning and inner porosity and their effects on Schwann cells
Biomaterials
(2014) - et al.
Growth mechanism of hydroxyapatite-coatings formed on pure magnesium and corrosion behavior of the coated magnesium
Appl. Surf. Sci.
(2011) - et al.
Innovative micro-textured hydroxyapatite and poly(L-lactic)-acid polymer composite film as a flexible, corrosion resistant, biocompatible, and bioactive coating for Mg implants
Mater. Sci. Eng. C-Mater.
(2017) - et al.
Production and bio-corrosion resistance of porous magnesium with hydroxyapatite coating for biomedical applications
Mater. Lett.
(2013) - et al.
Compressibility of porous magnesium foam: dependency on porosity and pore size
Mater. Lett.
(2004) - et al.
Processing of biocompatible porous Ti and Mg
Scr. Mater.
(2001)
Preparation, mechanical properties and in vitro biodegradation of porous magnesium scaffolds
Mater. Sci. Eng. C-Biol. S
Loss of hydroxyapatite coating on retrieved, total hip components
J. Arthroplasty
Chapter 2 – Overview of Bone Structure and Strength A2 – Thakker, Rajesh V
Corrosion protection of magnesium alloy AZ31 sheets by spin coating process with poly(ether imide) [PEI]
Corros. Sci.
Corrosion protection of magnesium AZ31 alloy using poly(ether imide) [PEI] coatings prepared by the dip coating method Influence of solvent and substrate pre-treatment
Corros. Sci.
Corrosion protection of magnesium alloy AZ31 by coating with poly(ether imides) (PEI)
Surf. Coat. Technol.
Improvement of surface bioactivity of poly(lactic acid) biopolymer by sandblasting with hydroxyapatite bioceramic
Mater. Lett.
Polyetheretherketone/magnesium composite selectively coated with hydroxyapatite for enhanced in vitro bio-corrosion resistance and biocompatibility
Mater. Lett.
A bioactive coating of a silica xerogel/chitosan hybrid on titanium by a room temperature sol-gel process
Acta Biomater.
Microstructure and compression properties of 3D powder printed Ti-6Al-4V scaffolds with designed porosity: experimental and computational analysis
Mater. Sci. Eng. C
Dependence of yield strain of human trabecular bone on anatomic site
J. Biomech.
How useful is SBF in predicting in vivo bone bioactivity?
Biomaterials
In vitro and in vivo evaluation of biodegradable, open-porous scaffolds made of sintered magnesium W4 short fibres
Acta Biomater.
MgF2-coated porous magnesium/alumina scaffolds with improved strength, corrosion resistance, and biological performance for biomedical applications
Mater. Sci. Eng. C-Mater.
Additively manufactured biodegradable porous magnesium
Acta Biomater.
Fabrication methods of porous metals for use in orthopaedic applications
Biomaterials
Effect of sintering conditions on the microstructural and mechanical characteristics of porous magnesium materials prepared by powder metallurgy
Mater. Sci. Eng. C-Mater.
Microstructure and mechanical properties of sintered porous magnesium using polymethyl methacrylate as the space holder
Mater. Lett.
Properties of porous magnesium prepared by powder metallurgy
Mater. Sci. Eng. C-Mater.
The mechanical-properties of trabecular bone – dependence on anatomic location and function
J. Biomech.
Porosity of 3D biomaterial scaffolds and osteogenesis
Biomaterials
The mechanical behaviour of cancellous bone
J. Biomech.
Preparation and mechanical property of a novel 3D porous magnesium scaffold for bone tissue engineering
Mater. Sci. Eng., C
Effect of sintering conditions on the microstructural and mechanical characteristics of porous magnesium materials prepared by powder metallurgy
Mater. Sci. Eng., C
Porosity and pore size effect on the properties of sintered Ti35Nb4Sn alloy scaffolds and their suitability for tissue engineering applications
J. Alloy. Compd.
Fabrication of hydrophobic surface with hierarchical structure on Mg alloy and its corrosion resistance
Electrochim. Acta
Preparation and corrosion resistance of a nanocomposite plasma electrolytic oxidation coating on Mg-1%Ca alloy formed in aluminate electrolyte containing titania nano-additives
J. Alloy. Compd.
Hemocompatibility and selective cell fate of polydopamine-assisted heparinized PEO/PLLA composite coating on biodegradable AZ31 alloy
Colloid Surf. B
Corrosion resistance of a composite polymeric coating applied on biodegradable AZ31 magnesium alloy
Acta Biomater.
Characteristics and cytocompatibility of biodegradable polymer film on magnesium by spin coating
Colloid Surf. B
In vivo corrosion of four magnesium alloys and the associated bone response
Biomaterials
In vivo degradation behavior of Ca-deficient hydroxyapatite coated Mg–Zn–Ca alloy for bone implant application
Colloids Surf. B
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