Biodegradable polymer-based nanocomposite coatings provide multiple advantages to modulate the corrosion resistance and cytocompatibility of magnesium (Mg) alloys for biomedical applications. Biodegradable poly(glycerol sebacate) (PGS) is a promising candidate used for medical implant applications. In this study, we synthesized a new PGS nanocomposite system consisting of hydroxyapatite (HA) and magnesium oxide (MgO) nanoparticles and developed a spray coating process to produce the PGS nanocomposite layer on pretreated Mg substrates, which improved the coating adhesion at the interface and their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs). Prior to the spray coating process of polymer-based nanocomposites, the Mg substrates were pretreated in alkaline solutions to enhance the interfacial adhesion strength of the polymer-based nanocomposite coatings. The addition of HA and MgO nanoparticles (nHA and nMgO) to the PGS matrix, as well as the alkaline pretreatment of the Mg substrates, significantly enhanced the interfacial adhesion strength when compared with the PGS coating on the nontreated Mg control. The average BMSC adhesion densities were higher on the PGS/nHA/nMgO coated Mg than the noncoated Mg controls under direct contact conditions. Moreover, the addition of nHA and nMgO to the PGS matrix and coating the nanocomposite onto Mg substrates increased the average BMSC adhesion density when compared with the PGS/nHA/nMgO coated titanium (Ti) and PGS coated Mg controls under direct contact. Therefore, the spray coating process of PGS/nHA/nMgO nanocomposites on Mg substrates or other biodegradable metal substrates could provide a promising surface treatment strategy for biodegradable implant applications.

Magnesium (Mg) and its alloys have attracted increasing attention in recent years as medical implants for repairing musculoskeletal injuries because of their promising mechanical and biological properties. However, rapid degradation of Mg and its alloys in physiological fluids limited their clinical translation because the accumulation of hydrogen (H₂) gas and fast release of OH^- ions could adversely affect the healing process. Moreover, infection is a major concern for internally implanted devices because it could lead to biofilm formation, prevent host cell attachment on the implants, and interfere osseointegration, resulting in implant failure or other complications. Fabricating nanostructured magnesium oxide (MgO) on magnesium (Mg) substrates is promising in addressing both problems because it could slow down the degradation process and improve the antimicrobial activity. In this study, nanostructured MgO layers were created on Mg substrates using two different surface treatment techniques, i.e., anodization and electrophoretic deposition (EPD), and cultured with Staphylococcus aureus in vitro to determine their antimicrobial properties. At the end of the 24-h bacterial culture, the nanostructured MgO layers on Mg prepared by anodization or EPD both showed significant bactericidal effect against S. aureus. Thus, nanostructured MgO layers on Mg are promising for reducing implant-related infections and complications and should be further explored for clinical translation toward antimicrobial biodegradable implants.

A portable device was designed and constructed for studying the properties of biomaterials in physiologically relevant fluids under controllable flow conditions that closely simulate fluid flow inside the body. The device can fit entirely inside a cell incubator; and, thus, it can be used directly under standard cell culture conditions. An impedance-driven pump was built in the sterile flow loop to control the flow rates of fluids, which made the device small and portable for easy deployment in the incubator. To demonstrate the device functions, magnesium (Mg) as a representative biodegradable material was tested in the flow device for immersion degradation under flow versus static conditions, while the flow module was placed inside a standard cell incubator. The flow rate was controlled at 0.17 ± 0.06 ml/s for this study; and, the flow rate is adjustable through the controller module outside of incubators for simulating the flow rates in the ranges of blood flow in human artery (0.05 ∼0.43 ml/s) and vein (0.02 ∼0.08 ml/s). Degradation of Mg under flow versus static conditions was characterized by measuring the changes of sample mass and thickness, and Mg²⁺ ion concentrations in the immersion media. Surface chemistry and morphology of Mg after immersion under flow versus static conditions were compared. The portable impedance-driven flow device is easy to fit inside an incubator and much smaller than a peristaltic pump, providing a valuable solution for studying biomaterials and implants (e.g. vascular or ureteral stents) in body fluids under flow versus static conditions with or without cells.

Magnesium (Mg) and its alloys have shown attractive biocompatibility and mechanical strength for medical applications, but low corrosion resistance of Mg in physiological environment limits its broad clinical translation. Hydroxyapatite (HA) nanoparticles (nHA) are promising coating materials for decreasing degradation rates and prolonging mechanical strength of Mg-based implants while enhancing bone healing due to their osteoconductivity and osteoinductivity. Conformal HA coatings with nano-to-submicron structures, namely nHA and mHA coatings, were deposited successfully on Mg plates and rods using a transonic particle acceleration (TPA) process under two different conditions, characterized, and investigated for their effects on Mg degradation in vitro. The nHA and mHA coatings enhanced corrosion resistance of Mg and retained 86-90% of ultimate compressive strength after in vitro immersion in rSBF for 6 weeks, much greater than non-coated Mg that only retained 66% of strength. Mg-based rods with or without coatings showed slower degradation than the respective Mg-based plates in rSBF after 6 weeks, likely because of the greater surface-to-volume ratio of Mg plates than Mg rods. This indicates that Mg-based plate and screw devices may undergo different degradation even when they have the same coatings and are implanted at the same or similar anatomical locations. Therefore, in addition to locations of implantation, the geometry, dimension, surface area, volume, and mass of Mg-based implants and devices should be carefully considered in their design and processing to ensure that they not only provide adequate structural and mechanical stability for bone fixation, but also support the functions of bone cells, as clinically required for craniomaxillofacial (CMF) and orthopedic implants. When the nHA and mHA coated Mg and non-coated Mg plates were cultured with bone marrow derived mesenchymal stem cells (BMSCs) using the in vitro direct culture method, greater cell adhesion densities were observed under indirect contact conditions than that under direct contact conditions for the nHA and mHA coated Mg. In comparison with non-coated Mg, the nHA and mHA coated Mg reduced BMSC adhesion densities directly on the surface, but increased the average BMSC adhesion densities under indirect contact. Further long-term studies in vitro and in vivo are necessary to elucidate the effects of nHA and mHA coatings on cell functions and tissue healing.

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.

Magnesium-zinc-calcium (Mg-Zn-Ca) alloys have attracted increasing attention for biomedical implant applications, especially for bone repair, because of their biocompatibility, biodegradability, and similar mechanical properties to human bone. The objectives of this study were to characterize Mg-2 wt % Zn-0.5 wt % Ca (named ZC21) alloy pins microstructurally and mechanically, and determine their degradation and interactions with host cells and pathogenic bacteria in vitro and in vivo in comparison with the previously studied Mg-4 wt % Zn-1 wt % strontium (named ZSr41) alloy and Mg control. Specifically, the in vitro degradation and cytocompatibility of ZC21 pins with bone marrow derived mesenchymal stem cells (BMSCs) were investigated using both direct culture and direct exposure culture methods. The adhesion density of BMSCs on ZC21 pins (i.e., direct contact) was significantly higher than on pure Mg pins in both in vitro culture methods; the cell adhesion density around ZC21 pins (i.e., indirect contact) was similar to the cell-only positive control in both in vitro culture methods. Interestingly, ZC21 showed a higher daily degradation rate, crack width and crack area ratio in the direct exposure culture than in the direct culture, suggesting different culture methods did affect its in vitro degradation behaviors. When cultured with Gram-positive bacteria methicillin-resistant Staphylococcus aureus (MRSA), ZC21 reduced bacterial adhesion on the surface more significantly than that of ZSr41 and Mg. The in vivo degradation and biocompatibility of the ZC21 pins for bone regeneration were studied in a mouse femoral defect model. The in vivo degradation rate of ZC21 pins was much slower than that of ZSr41 alloy and Mg control pins. After 12 weeks of implantation in vivo, the ZC21 group showed the shortest gap at the femoral defect, indicating that ZC21 pins promoted osteogenesis and bone healing more than ZSr41 and Mg control pins. Overall, the ZC21 alloy is promising for bone repair, while providing antibacterial activities, and should be further studied toward clinical translation.