A Biodegradable Zinc Alloy Membrane with Regulation of Macrophage Polarization for Early Vascularized Bone Regeneration
Yi Li, Ruimin Tang, Chunsheng Shao, Chang Chen, Jiangjie Tang, Luman Liao, Liangjian Chen
Abstract
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 Zn 2+ 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.