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

mechanism to maintain iron homeostasis, and the slow (VEGF-R2), which in turn promote angiogenesis. 66,67 The
degradation of iron-based scaffolds and the difficulty in production of reactive oxygen species (ROS) and the slow
metabolizing the products prevent large changes in plasma and steady release of metal ions from magnesium oxide
iron levels. 46-48 If an implant is not loaded with other or zinc oxide nanoparticles can promote vascularization,
substances or if alloying elements with osteogenic effects but importantly, an excessive concentration of zinc ions
are added, iron-based implants have a weak osteogenic can instead inhibit angiogenesis. 68,69 Iron itself has no
effect in vivo. 49,50 pro-vascularization activity, but iron oxide nanoparticles

Among the three BM materials tested, magnesium has can be used in conjunction with electromagnetic fields to
a strong and stable osteogenic differentiation effect, zinc is magnetically transfect the miR-21 gene into bone marrow
slightly inferior due to its ability to inhibit osteogenesis at mesenchymal stem cells (BMSCs) and human umbilical
higher concentrations and cytotoxicity, and the osteogenic cord endothelial cells (HUVECs), and the transfected cells
differentiation effect of iron in vivo has rarely been reported. can be loaded onto implants to promote vascularization
and osteogenesis. In general, magnesium has a stronger
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2.2. Antibacterial effects of BMs ability to promote vascular activity than zinc does, while
In addition to antibiotics, metals are a focus of the effect of iron is weaker than that of both.
current research seeking antibacterial substances. The
antimicrobial effect of zinc originates from its ability to 3. Common 3D printing techniques for BMs
bind and disrupt bacterial cell membranes and membrane
proteins, alter cellular permeability to calcium ions, and Three-dimensional printing techniques for BM materials
disrupt oxidoreductase enzymes in the electron transport can be broadly categorized into 3D printing of BMs and
system, and the antimicrobial effect of free zinc ions shows their alloys, and 3D printing of nonmetallic materials
a dose-dependent effect. The zinc ions released from mixed with BM materials. The two manufacturing
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pure zinc implants during degradation have significant methods used were pure metal scaffolds and hybrid
antimicrobial effects, and the antimicrobial capacity of material scaffolds. The 3D printing methods commonly
implants can be further strengthened by adding silver and used for metals can be categorized into four main groups:
lithium to form alloys. 52,53 The addition of zinc or zinc ions powder bed fusion (PBF), direct energy deposition
to nonbiodegradable metal scaffolds has also been shown (DED), material extrusion (ME), and binder jetting
to confer antimicrobial activity to the components. 54-56 In (BJ). 71,72 The most commonly used and most effective
addition to zinc ions, metals that form nanoparticles can method for implant fabrication is PBF, which is more
also exert antimicrobial effects. NPs can interact with accurate than the other methods, can print highly complex
bacterial cell membranes, leading to leakage, inducing components, can generate finished products with strong
oxidative stress, and ultimately leading to bacterial mechanical properties, and is better suited to the needs of
death. Zinc nanooxide, magnesium nanooxide, and iron clinical implants. 73,74 Table 1 displays the advantages and
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nanooxide have strong antibacterial effects. 58-60 Among disadvantages of each 3D printing method.
the three degradable metallic materials, magnesium, iron, 3.1. Three-dimensional printing of BMs by powder
and zinc have the most prominent antimicrobial activity, bed fusion
while magnesium and iron are slightly inferior and exert Powder bed fusion is an additive manufacturing process
antimicrobial activity only when used as nanooxides.
in which metal powders in a powder bed are bonded and
2.3. Vascularization induced by BMs sintered using thermal energy, with the energy source
Both magnesium and zinc can promote vascularization. usually being a laser or an electron beam. The material
Magnesium can promote endothelial cell migration in a is preheated in a vacuum or inert gas environment,
dose-dependent manner, upregulate vascular endothelial and a laser or electron beam is used to selectively sinter
growth factor, and promote CGRP-mediated angiogenesis a portion of the powder in the powder bed to form a
to promote neovascularization and prevent vascular crystalline metal layer, followed by a drop of the powder
leakage. 61,62 The use of magnesium-based implants or bed, where the new metal powder covers the sintered
the addition of magnesium to implants can promote metal layer, on which sintering is performed again, and
vascularization and thus accelerate bone regeneration. 63-65 the procedure is repeated until the metal component is
Zinc ions can upregulate the gene expression of printed. 75,76 The advantages of PBF include high precision,
angiopoietin-2 (ANG2), epidermal growth factor (EGF), control, suitability for metallic materials, and the ability to
and fibroblast growth factor (FGF) and increase the create porous structures by adding other substances (e.g.,
protein levels of vascular endothelial growth factor-A diamond). 77,78 The disadvantages of PBF include sputtering
(VEGF-A) and vascular endothelial growth factor-R2 and metal vaporization. Especially for magnesium alloys,

Volume 10 Issue 3 (2024) 42 doi: 10.36922/ijb.2460