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International Journal of Bioprinting 3D-printed biodegradable metals for bone regeneration

Figure 2. Mechanisms of bone regeneration by biodegradable metals. (A) Magnesium promotes osteogenesis by inducing MC3T3-E1 cells to secrete platelet-
derived growth factor BB (PDGF-BB), activating the CGRP–FAK–VEGF signaling pathway, exerting synergistic effects with bone morphogenetic protein
2 (BMP2), and upregulating the expression of transforming receptor potential cation channel subfamily M member 7 (TRPM7); Zrt and Irt-like proteins
(ZIPs) and zinc transporters (ZnTs) maintain zinc homeostasis; zinc can activate the Runt-related transcription factor 2 (Runx2) and P38 MAPK pathways,
inhibit the nuclear factor kappa B (NF-κB) pathway, and promote osteogenesis and inflammation; and iron has no osteogenic effect. (B) The antimicrobial
effect of zinc originates from its ability to inhibit oxidoreductase activity in the electron transport system and its ability to bind and destroy bacterial cell
membranes and membrane proteins; zinc oxide nanoparticles, magnesium oxide, and iron oxide exhibit antimicrobial effects by destroying cell membranes.
(C) Vascularization promotes osteogenesis; zinc ions upregulate angiopoietin-2 (ANG2), epidermal growth factor (EGF), and fibroblast growth factor (FGF)
gene expression and increase vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor-R2 (VEGF-R2) protein levels, which
in turn promote angiogenesis; magnesium increases VEGF protein levels and promotes calcitonin gene-related peptide (CGRP)-mediated angiogenesis;
zinc nanooxide and magnesium oxide generate reactive oxygen species (ROS) and slowly and stably release metal ions to promote vascularization; and iron
nanooxide promotes vascularization by performing magnetic transfection for gene modification, indirectly promoting vascularization.

but also influences intrachondral osteogenesis through its the RANKL/RANK/OPG signaling pathway in osteoclast
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involvement in terminal cartilage differentiation. Zinc precursors. Zinc can also exert anti-inflammatory effects
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also promotes the accumulation and deposition of citrate in by activating the P38 MAPK pathway and inhibiting
bone apatite. In bone tissue, the zinc content is positively the nuclear factor kappa B (NF-κB) pathway, but a high
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correlated with whole-body bone mineral density (BMD) concentration of zinc ions leads to overactivation of NF-κB
and bone mineral content (BMC). Additionally, zinc signaling and thus induces osteoclastogenesis. 43-45
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inhibits stimulation of RANKL (receptor activator of NF- Iron is an essential trace element. Although iron in
KB ligand) and suppresses osteoclastogenesis through implants undergoes in vivo degradation, cells possess a

Volume 10 Issue 3 (2024) 41 doi: 10.36922/ijb.2460