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. 2023 Jun 9;15(6):1700. doi: 10.3390/pharmaceutics15061700

Table 2.

Different functions of various ions in hydrogels.

Ions Function Mechanism Methodology Reference
Silicon ion Vascularization
  1. Promote the expression of angiogenesis-related factors in vascular endothelial cells.

  2. Stimulate in vitro migration, differentiation and tubule-like formation of vascular endothelial cells.

Use a novel calcium phosphate cement (CPC) as the basis for a scaffold that combined mesoporous silica (MS) with recombinant human bone morphogenetic protein-2 (rhBMP-2). [77]
Magnesium ion Vascularization
  1. Stimulate the proliferation of HUVEC.

  2. Increase its response to some motogenic factors.

  3. Upregulate integrin function and thus promote endothelial cell migration.

Fabricated Mg-doped β-TCP (Mg-TCP) scaffolds by 3D printing and sintering, in which MgO was mixed in different ratios. [78]
Make Ta-PDA-Mg scaffolds by doping Mg2+ on the surface of 3D printed tantalum scaffolds by using the surface adhesion ability of polydopamine. [79]
Immunomodulation
  1. Increase IκBα levels, and lead to reduced NF-κB activation and secretion of proinflammatory cytokines.

  2. Inhibit Notch1 protein expression to exert anti-inflammatory effects.

Load magnesium ions in the form of Mg-MOF-74 into 3D bioprinted scaffolds to exert anti-inflammatory effects in combination with icariin. [80]
Zinc ions Antibacterial
  1. The negative charge of the bacterial film, an electrostatic reaction between the film and the oppositely charged ZnO nanoparticles leads to the rupture of the film eventually triggering bacterial death.

  2. ZnO nanoparticles can release free Zn ions to disrupt the internal ionic homeostasis of the bacterium and subsequently lead to the death of the bacterium.

Made yttrium oxide-stabilized zirconium oxide (3Y-ZrO2) nanopowder into 3Y-ZrO2 ceramic by 3D printing, mold plasticity, and sintering. Then the ISO resin was uniformly coated onto the ceramic. Subsequently, ZnO nanosolution was dropped on this ceramic to finally produce ZnO-ISO bilayer modified ceramics. [81]
Copper ion Vascularization
  1. Stimulate endothelial cell proliferation and differentiation.

  2. Stimulates angiogenesis by mimicking hypoxia, stabilizing the expression of hypoxia-inducible factor (HIF-1a) and promoting the expression of VEGF.

Prepared a novel metal-organic framework, a β-tricalcium phosphate (Cu-TCPP-TCP) scaffold containing a copper coordinated tetrakis (4-carboxyphenyl) porphyrin (Cu-TCPP) nanosheet interfacial structure, by using 3D printing technology. [82]
Antibacterial
  1. Highly toxic hydroxyl radicals produced by copper can oxidize with most bacterial macromolecules to exert antibacterial effects.

  2. Associate with affecting the bacterial outer membrane potential, leading to the rupture of the bacterial membrane, and eventually to bacterial death.

Used 3D printing technology to prepare nanocomposites of medical grade polyamide 12 (PA12) with copper oxide (cuprous oxide) in different ratios. [83]
Immunomodulation Inhibit the activation of macrophages and suppress the synthesis and release of inflammatory factors. Made Cu-BGC scaffolds by incorporating different concentrations of copper (0.781–25 mg/mL) into bioactive microcrystalline glass using 3D printing technology. [84]
Regulation of collagen deposition Upregulate hypoxia-inducible factor-1 (HIF-1) expression and stimulates the expression of SOX-9, which leads to increased levels of COL II and ACAN expression. Fabricated Cu-BGC scaffolds by doping different concentrations of copper (0.781–25 mg/mL) into bioactive microcrystalline glass with 3D printing technology.
Silver ion Antibacterial
  1. Anchoring of AgNps on bacterial membranes leading to rupture of bacterial membranes and leakage of bacterial contents, resulting in bacterial cell death.

  2. Nanoparticles can penetrate into bacterial membranes and interact with biomolecules, resulting in bacterial dysfunction.

  3. AgNps may catalyze the reduction in O2 to reactive oxygen species (ROS), leading to downregulation of antioxidant enzyme expression, DNA damage and apoptosis.

Silver is mainly used in the form of metallic silver nanoparticles (AgNPs).
Designed a superporous polyacrylamide (PAM)/Hydroxypropyl Methyl Cellulose (HPMC) hydrogel with antibacterial ability by using silver-ethylene interactions and 3D printing technology.
[85]