Fundamental study of the development and evaluation of biodegradable Mg-Y-Ca-Zr based alloys as novel implant materials

Degradable metals hold considerable promise as materials which exhibit higher mechanical properties than degradable polymers while corroding over time to alleviate complications such as stress-shielding and infection that is inherent to permanent, bioinert metallic biomaterials. Specifically, degradable magnesium (Mg) alloys have emerged as a promising alternative for orthopedic and craniofacial applications due to their positive bone remodeling behavior, good biocompatibility, and relatively high strength compared to polymers while exhibiting similar stiffness to natural bone. Increasing the strength to maintain device integrity during degradation while simultaneously controlling the rapid corrosion of Mg to reduce the risk of hydrogen gas accumulation and toxicity are ongoing paramount goals for optimizing Mg alloys for musculoskeletal applications. In order to address these goals, novel Mg-Y-Ca-Zr based alloys were developed with alloying elements judiciously selected to impart favorable properties. Processing techniques including solution heat treatment combined with hot extrusion were employed to further enhance the desired properties of the material namely, controlled corrosion, high strength and ductility, and minimal toxic response. Increasing the Y content contributed to improved corrosion resistance yielding corrosion rates similar to commercial Mg alloys. Hot extrusion was employed to reduce the grain size, thereby improving mechanical properties through the Hall-Petch relation. Extrusion yielded extremely high strength relative to other Mg alloys, values approaching that of iron-based alloys, due to the presence of Mg12YZn, a long period stacking order phase that served to impede dislocation propagation. Both as-cast and extruded Mg-Y-Ca-Zr alloys demonstrated excellent in vitro cytocompatibility eliciting high viability and proliferation of MC3T3 pre-osteoblast cells and human mesenchymal stem cells. Alloying elements Y and Zr were specifically shown to improve cell proliferation. Finally, implantation of Mg-Y-Ca-Zr based alloys into the mouse subcutaneous tissue and intramedullary cavities of fractured rat femurs resulted in a normal host response and fracture healing, without eliciting any local or systemic toxicity. Thus, the alloys investigated in this work demonstrated great potential for applications as orthopedic and craniofacial implant biomaterials, warranting additional pre-clinical safety and efficacy trials that will be conducted in the near future