Bioactive Zn-0.6Cu thin sheet for craniofacial bone repair: In vitro and in vivo evaluations

Millions of craniofacial surgeries are performed annually worldwide, and materials for craniofacial bone repair are widely needed. However, traditionally applied materials, such as titanium and polymethylmethacrylate, have some shortcomings (limited malleability, material-based toxicity, non-biodegradability, lack of bioactivity, etc.). Zinc based biodegradable metals possess superior mechanical properties, biodegradability, and bioactivity, which make them promising candidate materials. Here, we successfully fabricated Zn-0.6Cu thin sheets (thickness ≤0.5 mm, suitable for craniofacial surgery) through combined extrusion and rolling. The in vitro and in vivo performances were generally evaluated and compared to those of a commercially applied pure titanium mesh. The mechanical properties of Zn-0.6Cu sheets were superior to those of clinically used polymethyl methacrylate. They were easy to shape and would not fracture during deformation. The Zn-0.6Cu sheet exhibited a gentle degradation mode, and proper implant-derived Zn improved osteogenic differentiation of rat bone marrow mesenchymal stem cells by up-regulating expression of osteogenesis related genes (alkaline phosphatase, bone morphogenetic protein-2). Thus, it further promoted extracellular matrix mineralization by improving calcium deposition for bone formation. It also improved the expression of angiogenesis-related genes (vascular endothelial growth factor, hypoxia-inducible factor alpha). The Zn-0.6Cu sheet exhibited high osteogenic activity in a cranial defect animal model compared to a non-biodegradable pure titanium mesh. Significant surface degradation occurred after two months in vivo, and degradation products were compatible with surrounding tissues. In general, the Zn-0.6Cu thin sheet seems to be a bioactive material selection for craniofacial bone repair, which might possibly accelerate defect repair and prevent adverse complications.