Table 2.
Summary of studies incorporating different ions within ceramic biomaterials.
| Type of ion incorporated | Type of biomaterial | Ion incorporation methodology | Content of ion incorporated | Ion release rate or amount of ion released | Effect on osteogenesis | References |
|---|---|---|---|---|---|---|
| Copper | Mesoporous bioactive glass | Solid block sintering | 5% molar ratio (Copper to Calcium and Silicon) | ≈2403 μM# | ↑ALP, OPN, OCN expression | Wu et al., 2013 |
| Calcium polyphosphate doped with copper | Solid block sintering | 0.1 % molar ratio (Copper to Calcium) | N/A | ↑ ALP, OCN expression and calcium node ↑ New bone area |
Li Y. et al., 2018 | |
| Bioactive silicate (13–93) doped with copper | Solid block sintering | 2 wt% [CuO to silicate (13–93)] | ≈ 16–222 μM* | ↓ proliferation and ALP activity ↓ bone formation |
Lin et al., 2016 | |
| Cobalt | Hydroxyapatite doped with cobalt | Ionic solution within liquid phase | 1 %wt (cobalt to calcium) | 0.14 μM# | ↑ Cell proliferation ↑ Runx-2, Osterix expression |
Kulanthaivel et al., 2016 |
| Hydroxyapatite nanoparticles doped with cobalt | Solid block sintering | 12 wt% (cobalt to calcium) | N/A | ↑ Mineralization rate ↑ Density and bone surface |
Ignjatovic et al., 2015 | |
| Nanoparticles of cobalt-substituted hydroxyapatite | Solid block sintering | 5 and 12 wt% (cobalt to calcium) | N/A | ↓ Viability ↑ Osteogenesis ↑ Bone density |
Ignjatović et al., 2013 | |
| Silicon | Mesoporous SiO2 microparticles | Ionic solution within liquid phase | 100% silicon matrix | ≈35–141 μM* | ↑ ALP activity ↑ COL1, OCN, OPG/RANKL expression |
Mao et al., 2017 |
| Ca–Mg–Si containing bioceramics | Precipitation | N/A | 1908–9446 μM* | ↑ ALP activity ↑ Col I, OCN, ALPase, OPN, OCN expression |
Zhai et al., 2013 | |
| Zinc | Zinc containing tricalcium phosphate | Sintering | 45 mmol ZnCl2 per 100 g TCP | ≈ 31 μM# | ↑ ALP activity ↑ Bone formation |
Luo et al., 2014 |
| Zinc doped mesoporous hydroxyapatite microspheres | Sintering | 0.05 molar ratio | ≈ 86 μM# | ↑ Runx2, ALP, OCN expression ↑ New bone area |
Yu et al., 2017 | |
| Strontium | 45S5 bioactive glass | Solid block sintering | 50 and 100% molar ratio (Strontium to calcium) | N/A | ↑ ALP, COL1, OCN expression | Santocildes-Romero et al., 2015 |
| HA doped with strontium | Precipitation | 10% molar ratio (Strontium to Calcium) | 110 μM | No osteogenic effect | Chandran et al., 2018 | |
| Bone ceramic + strontium-substituted nanoHA coating | Physisorption + sintering | 10% molar ratio (Strontium to Calcium) | N/A | ↑ ALP activity ↑ Runx2, OCN expression ↑ New bone formation |
Li J. et al., 2018 | |
| β-TCP + strontium-containing phosphate-based glass (SPG) | Solid block sintering | 5, 10, 15 mass fraction (SPG to β-TCP) | ≈ 3–14 μM* | ↑ ALP activity ↑ OPN, OCN expression ↓ osteoclastic activity |
Tian et al., 2018 | |
| Strontium-substituted calcium phosphate silicate bioactive ceramic | Solid block sintering | 5, 10 and 20% molar ratio (SrCO3 to Calcium, Phosphate and Silicon) | 457 μM (5%)# 1,484 μM (10%)# 2,968 μM (20%)# |
↑ ALP activity ↑ Runx2, OCN, OPN, BSP expression ↑ Mineralization ↑ New bone formation |
Zeng et al., 2020 | |
| Magnesium | Macroporous HA/Ca/Mg scaffold | Sintering | Immersion in 75000 μM Mg2+ solution before sintering | 2000 μM# | ↑ ALP, COL1, OCN, OPN expression | Chu et al., 2018 |
| Calcium phosphate cement combined with magnesium | Ionic solution within liquid phase | 1:2 molar ratio (CaH4P2O8 to MgO) | 2000–2500 μM* | ↑ COL1, ALP, OCN expression | Zhang J. et al., 2015 | |
| Boron | B-mesoporous bioactive glass | Solid block sintering | 10% molar ratio (Boron to Silicon, Calcium and Phosphate) | ≈ 765 μM# | ↑ COL1, Runx2, ALP, OCN expression ↑ Mineralization ↑ New bone formation |
Wu et al., 2011; Yin et al., 2018 |
| Lithium | Lithium doped mesoporous silica nanospheres | Sintering | 5% wt (lithium to silicon) | ≈ 857 μM#
(0.5mg/ml nanospheres) |
↑ ALP activity ↑OPN, Runx2, ALP, OCN expression |
Zhang et al., 2018 |
| Lithium-doped calcium phosphate cement | Ionic solution within solid phase | 0.3 ml/g of 50 and 100 mM LiCl solution | 3,571 μM (50 mM LiCl)#
7,143 μM (100 mM LiCl)# |
↑ ALP activity ↑ Mineralization ↑ COL1, OCN, OPG, Runx2 ↑ New bone formation |
Li et al., 2017 |
#
Total amount released at the end of the experiment.
*
The minimum and the maximum amount released during the experiment (based on cell culture media change timepoints).
BMSC, bone mesenchymal stem cells (mBMSC, mouse; hBMSC, human; rBMSC, rat); ALP, alkaline phosphatase activity; COL1, collagen type I; OPN, osteopontin; Runx-2, Runt-related transcription factor 2; OCN, osteocalcin; RANKL, Receptor Activator for Nuclear Factor κ B Ligand; HA, hydroxyapatite; TCP, Tricalcium phosphate; BSP, Bone sialoprotein; OPG, osteoprotegerin.
↑increase; ↓decrease.