Additive manufacturing of degradable metallic scaffolds for material-structure-driven diabetic maxillofacial bone regeneration

The regeneration of maxillofacial bone defects associated with diabetes mellitus remains challenging due to the occlusal loading and hyperglycemia microenvironment. Herein, we propose a material-structure-driven strategy through the additive manufacturing of degradable Zn–Mg–Cu gradient scaffolds. The in situ alloying of Mg and Cu endows Zn alloy with admirable compressive strength for mechanical support and uniform degradation mode for preventing localized rupture. The scaffolds manifest favorable antibacterial, angiogenic, and osteogenic modulation capacity in mimicked hyperglycemic microenvironment, and Mg and Cu promote osteogenic differentiation in the early and late stages, respectively. In addition, the scaffolds expedite diabetic maxillofacial bone ingrowth and regeneration by combining the metabolic regulation effect of divalent metal cations and the hyperboloid and suitable permeability of the gradient structure. RNA sequencing further reveals that RAC1 might be involved in bone formation by regulating the transport and uptake of glucose related to GLUT1 in osteoblasts, contributing to cell function recovery. Inspired by bone healing and structural cues, this study offers an essential understanding of the designation and underlying mechanisms of the material-structure-driven strategy for diabetic maxillofacial bone regeneration.