DEVELOPMENT OF HIGH STRENGTH BIODEGRADABLE METALS FOR BONE REPAIR

After two decades of research and development of biodegradable metallic materials, Mg-based, Fe-based and Zn-based biodegradable metals (BMs) had been widely studied by in vitro and in vivo biocompatibility testing. There were WE43 Mg alloy and Mg-Ca-Zn alloy bone screws being clinically used in Europe and China, Nitride Fe bioresorbable vascular scaffold being CE marked and clinically trailed in China, Zn-Mg-Fe alloy Maxillofacial bone screw being clinically trailed in China. For the mechanical strength viewpoint, the current Mg-based biodegradable metals is in generally below 350MPa and it can only be suitable for low load-bearing application in regenerative medicine, whereas the Zn-based biodegradable metals had been explored, with the Zn-Li based alloys exhibiting the tensile strength around 600MPa, close to that of the pure Ti and stainless steel, and is applicable for the medium load-bearing application in regenerative medicine. The Fe-based biodegradable metals had shown higher mechanical strength, but the majority of biometal society believe that Fe-based BMs is unsuitable for orthopaedic applications since element iron does not exist in the bone. In this work, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.