Electrophoretic Deposition of Magnesium Oxide Nanoparticles on Magnesium: Processing Parameters, Microstructures, Degradation, and Cytocompatibility.

Magnesium (Mg) and its alloys are a class of promising materials for biodegradable orthopedic and craniomaxillofacial implants; however, rapid release of hydrogen gas remains a key challenge for clinical translation. This study reported the optimal parameters of electrophoretic deposition (EPD), at which magnesium oxide nanoparticles (nMgO) could be deposited onto Mg substrates with homogeneous surface morphology and elemental distribution. The results showed that the distribution and uniformity of the nMgO coatings on Mg improved when the nMgO concentration in ethanol increased and the time of applied voltage decreased. The nMgO-coated Mg showed a homogeneous surface and distinct degradation mode during the 9-day immersion studies in revised simulated body fluid (r-SBF) and Dulbecco's modified Eagle's medium (DMEM), when compared with the noncoated Mg controls. The nMgO coating initially mitigated hydrogen gas formation. The degradation layer on nMgO-coated Mg was thicker than the noncoated Mg and enriched with Ca and P that are favorable for skeletal implant applications. In the direct culture study with bone marrow derived mesenchymal stem cells (BMSCs) in vitro, the cell adhesion density and morphology were not affected by the solubilized degradation products released by the nMgO-coated Mg under indirect contact. However, at the cell-biomaterial interface, the cell spreading decreased under direct contact, possibly because of the continuous dynamic degradation of the samples. The electrophoretically deposited nMgO coatings on Mg-based medical implants should be further studied to improve the coating-substrate and cell-material interfaces for clinical applications.

In vitro evaluation of MgSr and MgCaSr alloys via direct culture with bone marrow derived mesenchymal stem cells.

Magnesium (Mg) and its alloys have been widely investigated as the most promising biodegradable metals to replace conventional non-degradable metals for temporary medical implant applications. New Mg alloys have been developed for medical applications in recent years; and the concept of alloying Mg with less-toxic elements have aroused tremendous interests due to the promise to address the problems associated with rapid degradation of Mg without compromising its cytocompatibility and biocompatibility. Of particular interests for orthopedic/spinal implant applications are the additions of calcium (Ca) and strontium (Sr) into Mg matrix because of their beneficial properties for bone regeneration. In this study, degradation and cytocompatibility of four binary MgSr alloys (Mg-xSr, x = 0.2, 0.5, 1 and 2 wt%) and four ternary MgCaSr alloys (Mg-1Ca-xSr, x = 0.2, 0.5, 1 and 2 wt%) were investigated and compared via direct culture with bone marrow-derived mesenchymal stem cells (BMSCs). The influence of the alloy composition on the degradation rates were studied and compared. Moreover, the cellular responses to the binary MgSr alloys and the ternary MgCaSr alloys were comparatively evaluated; and the critical factors influencing BMSC behaviors were discussed. This study screened the degradability and in vitro cytocompatibility of the binary MgSr alloys and the ternary MgCaSr alloys. Mg-1Sr, Mg-1Ca-0.5Sr and Mg-1Ca-1Sr alloys are recommended for further in vivo studies toward clinical translation due to their best overall performances in terms of degradation and cytocompatibility among all the alloys studied in the present work. STATEMENT OF SIGNIFICANCE: Traditional Mg alloys with slower degradation often contain aluminum or rare earth elements as alloying components, which raised safety and regulatory concerns. To circumvent unsafe elements, nutrient elements such as calcium (Ca) and strontium (Sr) were selected to create Mg-Sr binary alloys and Mg-Ca-Sr ternary alloys to improve the safety and biocompatibility of bioresorbable Mg alloys for medical implant applications. In this study, in vitro degradation and cellular responses to four binary Mg-xSr alloys and four ternary Mg-1Ca-xSr alloys with increasing Sr content (up to 2 wt%) were evaluated in direct culture with bone marrow derived mesenchymal stem cells (BMSCs). The roles of Sr and Ca in tuning the alloy microstructure, degradation behaviors, and BMSC responses were collectively compared in the BMSC direct culture system for the first time. The most promising alloys were identified and recommended for further in vivo studies toward clinical translation.

Degradation of Bioresorbable Mg-4Zn-1Sr Intramedullary Pins and Associated Biological Responses in Vitro and in Vivo.

This article reports the degradation and biological properties of as-drawn Mg-4Zn-1Sr (designated as ZSr41) and pure Mg (P-Mg) wires as bioresorbable intramedullary pins for bone repair. Specifically, their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs) and degradation in vitro, and their biological effects on peri-implant tissues and in vivo degradation in rat tibiae were studied. The as-drawn ZSr41 pins showed a significantly faster degradation than P-Mg in vitro and in vivo. The in vivo average daily degradation rates of both ZSr41 and P-Mg intramedullary pins were significantly greater than their respective in vitro degradation rates, likely because the intramedullary site of implantation is highly vascularized for removal of degradation products. Importantly, the concentrations of Mg2+, Zn2+, and Sr2+ ions in the BMSC culture in vitro and their concentrations in rat blood in vivo were all lower than their respective therapeutic dosages, i.e., in a safe range. Despite of rapid degradation with a complete resorption time of 8 weeks in vivo, the ZSr41 intramedullary pins showed a significant net bone growth because of stimulatory effects of the metallic ions released. However, proportionally released OH- ions and hydrogen gas caused adverse effects on bone marrow cells and resulted in cavities in surrounding bone. Thus, properly engineering the degradation properties of Mg-based implants is critical for harvesting the bioactivities of beneficial metallic ions, while controlling adverse reactions associated with the release of OH- ions and hydrogen gas. It is necessary to further optimize the alloy processing conditions and/or modify the surfaces, for example, applying coatings onto the surface, to reduce the degradation rate of ZSr41 wires for skeletal implant applications.