skip to main content

Title: Biodegradable Magnesium Bone Implants Coated with a Novel Bioceramic Nanocomposite
Magnesium (Mg) alloys are being investigated as a biodegradable metallic biomaterial because of their mechanical property profile, which is similar to the human bone. However, implants based on Mg alloys are corroded quickly in the body before the bone fracture is fully healed. Therefore, we aimed to reduce the corrosion rate of Mg using a double protective layer. We used a magnesium-aluminum-zinc alloy (AZ91) and treated its surface with micro-arc oxidation (MAO) technique to first form an intermediate layer. Next, a bioceramic nanocomposite composed of diopside, bredigite, and fluoridated hydroxyapatite (FHA) was coated on the surface of MAO treated AZ91 using the electrophoretic deposition (EPD) technique. Our in vivo results showed a significant enhancement in the bioactivity of the nanocomposite coated AZ91 implant compared to the uncoated control implant. Implantation of the uncoated AZ91 caused a significant release of hydrogen bubbles around the implant, which was reduced when the nanocomposite coated implants were used. Using histology, this reduction in the corrosion rate of the coated implants resulted in an improved new bone formation and reduced inflammation in the interface of the implants and the surrounding tissue. Hence, our strategy using a MAO/EPD of a bioceramic nanocomposite coating (i.e., diopside-bredigite-FHA) can more » significantly reduce the corrosion rate and improve the bioactivity of the biodegradable AZ91 Mg implant. « less
; ; ; ;
Award ID(s):
Publication Date:
Journal Name:
Page Range or eLocation-ID:
Sponsoring Org:
National Science Foundation
More Like this
  1. Magnesium (Mg) and its alloys are considered to be biodegradable metallic biomaterials for potential orthopedic implants. While the osteogenic properties of Mg alloys have been widely studied, few reports focused on developing a bifunctional Mg implant with osteogenic and angiogenic properties. Herein, a Mg-Sc-Sr alloy was developed, and this alloy’s angiogenesis and osteogenesis effects were evaluated in vitro for the first time. X-ray Fluorescence (XRF), X-ray diffraction (XRD), and metallography images were used to evaluate the microstructure of the developed Mg-Sc-Sr alloy. Human umbilical vein/vascular endothelial cells (HUVECs) were used to evaluate the angiogenic character of the prepared Mg-Sc-Sr alloy. A mix of human bone-marrow-derived mesenchymal stromal cells (hBM-MSCs) and HUVEC cell cultures were used to assess the osteogenesis-stimulating effect of Mg-Sc-Sr alloy through alkaline phosphatase (ALP) and Von Kossa staining. Higher ALP activity and the number of calcified nodules (27% increase) were obtained for the Mg-Sc-Sr-treated groups compared to Mg-treated groups. In addition, higher VEGF expression (45.5% increase), tube length (80.8% increase), and number of meshes (37.9% increase) were observed. The Mg-Sc-Sr alloy showed significantly higher angiogenesis and osteogenic differentiation than pure Mg and the control group, suggesting such a composition as a promising candidate in bone implants.
  2. Magnesium (Mg)-based alloys have the potential for bone repair due to their properties of biodegradation, biocompatibility, and structural stability, which can eliminate the requirement for a second surgery for the removal of the implant. Nevertheless, uncontrolled degradation rate and possible cytotoxicity of the corrosion products at the implant sites are known current challenges for clinical applications. In this study, we assessed in vitro cytotoxicity of different concentrations (0 to 50 mM) of possible corrosion products in the form of magnesium oxide (MgO) and magnesium hydroxide (Mg(OH)2) nanoparticles (NPs) in human fetal osteoblast (hFOB) 1.19 cells. We measured cell proliferation, adhesion, migration, and cytotoxicity using a real-time, label-free, non-invasive electric cell-substrate impedance sensing (ECIS) system. Our results suggest that 1 mM concentrations of MgO/Mg(OH)2 NPs are tolerable in hFOB 1.19 cells. Based on our findings, we propose the development of innovative biodegradable Mg-based alloys for further in vivo animal testing and clinical trials in orthopedics.
  3. Magnesium–yttrium-rare earth element alloys such as WE43 are potential candidates for future bioabsorbable orthopedic implant materials due to their biocompatibility, mechanical properties similar to human bone, and the ability to completely degrade in vivo . Unfortunately, the high corrosion rate of WE43 Mg alloys in physiological environments and subsequent loss of structural integrity limit the wide applications of these materials. In this study, the effect of chemical heterogeneity and microstructure on the corrosion resistance of two alloys with different metallurgical states was investigated: cast (as in traditional preparation) and as-deposited produced by magnetron sputtering. The corrosion behavior was studied by potentiodynamic polarization and electrochemical impedance spectroscopy tests in blood bank buffered saline solution. It was found that the as-deposited alloy showed more than one order of magnitude reduction in corrosion current density compared to the cast alloy, owing to the elimination of micro-galvanic coupling between the Mg matrix and the precipitates. The microstructure and formation mechanism of corrosion products formed on both alloys were discussed based on immersion tests and direct measurements of X-ray photoelectron spectrometry (XPS) and cross-sectional transmission electron microscopy (TEM) analysis.
  4. INTRODUCTION: Orthopedic implants are important therapeutic devices for the management of a wide range of orthopedic conditions. However, bacterial infections of orthopedic implants remain a major problem, and not an uncommon one, leading to an increased rate of osteomyelitis, sepsis, implant failure and dysfunction, etc. Treating these infections is more challenging as the causative organism protects itself by the production of a biofilm over the implant’s surface (1). Infections start by the adhesion and colonization of pathogenic bacteria such as Staphylococcus aureus (SA), Staphylococcus epidermidis (SE), Escherichia coli (E. coli), Methicillin-Resistant Staphylococcus aureus (MRSA), and Multi-Drug Resistant Escherichia coli (MDR E. coli) on the implant’s surfaces. Specifically, Staphylococcus comprises up to two-thirds of all pathogens involved in orthopedic implant infections (2). However, bacterial surface adhesion is a complex process influenced by several factors such as chemical composition, hydrophobicity, magnetization, surface charge, and surface roughness of the implant (3). Considering the intimate association between bacteria and the implant surface, we measured the effect of stainless-steel surface properties on bacterial surface attachment and subsequent formation of biofilms controlling above mentioned factors. METHODS: The prominent bacteria responsible for orthopedic implant infections (SA, SE, E. coli, MRSA, and MDR E. coli) were used inmore »this study. We were able to control the grain size of medical grade 304 and 316L stainless steel without altering their chemical composition (grain size range= 20μm-200nm) (4). Grain size control affected the nano-topography of the material surfaces which was measured by an Atomic Force Microscope (AFM). Grain sizes, such as 0.2, 0.5, 1, 2, 3, 9, and 10 μm, were used both polished and non-polished. All the stainless-steel samples were cleaned by treating with acetone and ethanol under sonication. Triplicates of all polished and non-polished samples with different grain sizes were subjected to magnetization of DM, 0.1T, 0.5T, and 1T, before seeding them with the bacteria. Controls were used in the form of untreated samples. Bacterial were grown in Tryptic Soy Broth (TSB). An actively growing bacterial suspension was seeded onto the stainless-steel discs into 24-well micro-titer plates and kept for incubation. After 24 hours of incubation, the stainless-steel discs were washed with Phosphate Buffer Saline (PBS) to remove the plankton bacteria and allow the sessile bacteria in the biofilm to remain. The degree of development of the bacterial biofilms on the stainless-steel discs were measured using spectrophotometric analysis. For this, the bacterial biofilm was removed from the stainless steel by sonication. The formation of biofilms was also determined by performing a biofilm staining method using Safranin. RESULTS SECTION: AFM results revealed a slight decrease in roughness by decreasing the grain size of the material. Moreover, the samples were segregated into two categories of polished and non-polished samples, in which polishing decreased roughness significantly. After careful analysis we found out that polished surfaces showed a higher degree for biofilm formation in comparison to the non-polished ones. We also observed that bacteria showed a higher rate for biofilm formation for the demagnetized samples, whereas 0.5T magnetization showed the least amount of biofilm formation. After 0.5T, there was no significant change in the rate of biofilm formation on the stainless-steel samples. Altogether, stainless steel samples containing 0.5 μm and less grainsize, and magnetized with 0.5 tesla and stronger magnets demonstrated the least degree of biofilm formation. DISCUSSION: In summary, the results demonstrate that controlling the grain size of medical grade stainless steel can control and mitigate bacterial responses on, and thus possibly infections of, orthopedic implants or other implantable devices. The research was funded by Komatsuseiki Kosakusho Co., Ltd (KSJ: Japan) SIGNIFICANCE/CLINICAL RELEVANCE: Orthopedic implants that more than 70% of them are made of metals (i.e., stainless steel, titanium, and cobalt-chromium alloys) are failing through loosening and breakage due to their limited mechanical properties. On the other hand, the risk of infection for these implants and its financial burden on our society is undeniable. We have seen that our uniformly nanograined stainless steel shows improved mechanical properties (i.e., higher stiffness, hardness, fatigue) as compared to conventional stainless steel along with the reduction of biofilm formation on its surface. These promising results made us to peruse the development of nanograined titanium and cobalt-chromium alloys for resolving the complications of orthopedic implants.« less
  5. Polymeric coatings can provide temporary stability to bioresorbable metallic stents at the initial stage of deployment by alleviating rapid degradation and providing better interaction with surrounding vasculature. To understand this interfacing biocompatibility, this study explored the endothelial-cytocompatibility of polymer-coated magnesium (Mg) alloys under static and dynamic conditions compared to that of non-coated Mg alloy surfaces. Poly (carbonate urethane) urea (PCUU) and poly (lactic-co-glycolic acid) (PLGA) were coated on Mg alloys (WE43, AZ31, ZWEKL, ZWEKC) and 316L stainless steel (316L SS, control sample), which were embedded into a microfluidic device to simulate a vascular environment with dynamic flow. The results from attachment and viability tests showed that more cells were attached on the polymer-coated Mg alloys than on non-coated Mg alloys in both static and dynamic conditions. In particular, the attachment and viability on PCUU-coated surfaces were significantly higher than that of PLGA-coated surfaces of WE43 and ZWEKC in both static and dynamic conditions, and of AZ31 in dynamic conditions (P<0.05). The elementary distribution map showed that there were relatively higher Carbon weight percentages and lower Mg weight percentages on PCUU-coated alloys than PLGA-coated alloys. Various levels of pittings were observed underneath the polymer coatings, and the pittings were more severemore »on the surface of Mg alloys that corroded rapidly. Polymer coatings are recommended to be applied on Mg alloys with relatively low corrosion rates, or after pre-stabilizing the substrate. PCUU-coating has more selective potential to enhance the biocompatibility and mitigate the endothelium damage of Mg alloy stenting.« less