Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy.

There has been a tremendous amount of research in the past decade to optimize the mechanical properties and degradation behavior of the biodegradable Mg alloy for orthopedic implant. Despite the feasibility of degrading implant, the lack of fundamental understanding about biocompatibility and underlying bone formation mechanism is currently limiting the use in clinical applications. Herein, we report the result of long-term clinical study and systematic investigation of bone formation mechanism of the biodegradable Mg-5wt%Ca-1wt%Zn alloy implant through simultaneous observation of changes in element composition and crystallinity within degrading interface at hierarchical levels. Controlled degradation of Mg-5wt%Ca-1wt%Zn alloy results in the formation of biomimicking calcification matrix at the degrading interface to initiate the bone formation process. This process facilitates early bone healing and allows the complete replacement of biodegradable Mg implant by the new bone within 1 y of implantation, as demonstrated in 53 cases of successful long-term clinical study.

Rapid in vitro corrosion induced by crack-like pathway in biodegradable Mg-10% Ca alloy.

The in vitro corrosion mechanism of the biodegradable cast Mg-10% Ca binary alloy in Hanks' solution was evaluated through transmission electron microscopy observations. The corrosion behavior depends strongly on the microstructural peculiarity of Mg2Ca phase surrounding the island-like primary Mg phase and the fast corrosion induced by the interdiffusion of O and Ca via the Mg2Ca phase of lamellar structure. At the corrosion front, we found that a nanosized crack-like pathway was formed along the interface between the Mg2Ca phase and the primary Mg phase. Through the crack-like pathway, O and Ca are atomically exchanged each other and then the corroded Mg2Ca phase was transformed to Mg oxides. The in vitro corrosion by the exchange of Ca and O at the nanosized pathway led to the rapid bulk corrosion in the Mg-Ca alloys.

Biocompatibility and strength retention of biodegradable Mg-Ca-Zn alloy bone implants.

The biocompatibility and strength retention of a Mg-Ca-Zn alloy were studied to evaluate its efficacy for osteosynthesis applications. Mg-Ca-Zn alloy and self-reinforced poly l-lactide (SR-PLLA) bone screws were implanted into New Zealand rabbits for radiography analysis, micro computed tomography analysis, histomorphometry, hematology, serum biochemistry, histopathology, and inductively coupled plasma mass spectrometry analysis. Bending and torsion tests were performed on intact specimens to find the initial mechanical strength of these Mg-Ca-Zn alloy bone screws. Strength retention of the Mg-Ca-Zn alloy implants were calculated from in vivo degradation rates and initial mechanical strength. Based on the animal study, Mg-Ca-Zn alloy bone screw showed absence of subcutaneous gas pockets, characteristic surface erosion properties, faster degradation rate than SR-PLLA bone screw, normal reference range of hematology and serum biochemistry, better histopathological response than SR-PLLA bone screw, and stable concentrations of each constituent element in soft tissues surrounding the implants. The initial strength and strength retention of Mg-Ca-Zn alloy were compared with those of various biomaterials. The initial strength of Mg-Ca-Zn alloy was higher than those of biostable and biodegradable polymers. The strength retention of Mg-Ca-Zn alloy bone screws was similar to those of biodegradable polymer. Therefore, this Mg-Ca-Zn alloy represents an excellent biodegradable biomaterial candidate for osteosynthesis applications.

Biodegradability engineering of biodegradable Mg alloys: tailoring the electrochemical properties and microstructure of constituent phases.

Crystalline Mg-based alloys with a distinct reduction in hydrogen evolution were prepared through both electrochemical and microstructural engineering of the constituent phases. The addition of Zn to Mg-Ca alloy modified the corrosion potentials of two constituent phases (Mg + Mg2Ca), which prevented the formation of a galvanic circuit and achieved a comparable corrosion rate to high purity Mg. Furthermore, effective grain refinement induced by the extrusion allowed the achievement of much lower corrosion rate than high purity Mg. Animal studies confirmed the large reduction in hydrogen evolution and revealed good tissue compatibility with increased bone deposition around the newly developed Mg alloy implants. Thus, high strength Mg-Ca-Zn alloys with medically acceptable corrosion rate were developed and showed great potential for use in a new generation of biodegradable implants.

Load-bearing capacity and biological allowable limit of biodegradable metal based on degradation rate in vivo.

In this study, a newly developed Mg-Ca-Zn alloy for low degradation rate and surface erosion properties was evaluated. The compressive, tensile, and fatigue strength were measured before implantation. The degradation behavior was evaluated by analyzing the microstructure and local hardness of the explanted specimen. Mean and maximum degradation rates were measured using micro CT equipment from 4-, 8-, and 16- week explants, and the alloy was shown to display surface erosion properties. Based on these characteristics, the average and minimum load bearing capacities in tension, compression, and bending modes were calculated. According to the degradation rate and references of recommended dietary intakes (RDI), the Mg-Ca-Zn alloy appears to be safe for human use.

In vivo corrosion mechanism by elemental interdiffusion of biodegradable Mg-Ca alloy.

We elucidated the in vivo corrosion mechanism of the biodegradable alloy Mg-10 wt % Ca in rat femoral condyle through transmission electron microscope observations assisted by focused ion beam technique. The alloy consists of a primary Mg phase and a three-dimensional lamellar network of Mg and Mg(2)Ca. We found that the Mg(2)Ca is rapidly corroded by interdiffusion of Ca and O, leading to a structural change from lamellar network to nanocrystalline MgO. In contrast to the fast corrosion rate of the lamellar structure, the primary Mg phase slowly changes into nanocrystalline MgO through surface corrosion by O supplied along the lamellar networks. The rapid interdiffusion induces an inhomogeneous Ca distribution and interestingly leads to the formation of a transient CaO phase, which acts as a selective leaching path for Ca. In addition, the outgoing Ca with P from body fluids forms needle-type calcium phosphates similar to hydroxyl apatite at interior and surface of the implant, providing an active biological environment for bone mineralization.