A Biodegradable Zinc Alloy Membrane with Regulation of Macrophage Polarization for Early Vascularized Bone Regeneration.

Guided bone regeneration (GBR) has become a standard modality for treating localized jawbone defects in the clinic. For optimal bone regeneration, the GBR membrane must be biodegradable and exhibit superior mechanical properties. Zinc, a biodegradable metal, has demonstrated marked potential for use in GBR membranes. To address the insufficient mechanical properties of pure zinc membranes, a Zn-0.3Fe-0.05Mg membrane with enhanced mechanical performance was developed in this study. The Young's modulus, hardness, ultimate tensile strength, and elongation at break of the Zn-0.3Fe-0.05Mg membrane were 47.94 ± 7.38 GPa, 0.58 ± 0.08 GPa, 294.07 ± 7.16 MPa, and 20.67% ± 0.15%, respectively, all of which were superior to those of the pure zinc membrane. Moreover, at a concentration of less than 25%, the membrane extract was not cytotoxic, while in the concentration range of 10% to 25% (zinc concentration of 37.33 ± 3.50 to 93.33 ± 8.75 μM), the membrane extract induced the M2 polarization of Raw264.7 cells. Then, at membrane extract concentrations of 10% to 25%, the osteogenic differentiation of MC3T3-E1 cells and vascularization of human umbilical vein endothelial cells (HUVECs) were promoted in the Raw264.7-MC3T3-E1 and Raw264.7-HUVEC coculture systems. Furthermore, scanning electron microscopy, microcomputed tomography, and histological analyses revealed that the Zn-0.3Fe-0.05Mg membrane promoted M2 macrophage polarization and angiogenesis in vivo, thereby facilitating early bone formation after 2 to 4 weeks. These findings suggest that the Zn-0.3Fe-0.05Mg membrane can degrade and release Zn²⁺ to regulate M2 macrophage polarization and promote early vascularized bone regeneration, showing the potential of Zn-0.3Fe-0.05Mg membranes as ideal GBR membranes.