Doped Calcium Silicate Ceramics: A New Class of Candidates for Synthetic Bone Substitutes
Abstract
:1. Introduction
- Ability to maintain in vivo mechanical stability at the defect site and withstand physiological loads.
- Radiopacity for easy implant monitoring using non-invasive methods such as X-ray and micro-computed tomography (µ-CT).
- Bioactivity to promote implant integration with host bone, as well as induce bone formation inside and surrounding the implant.
- Ability to be manufactured into macroporous scaffolds with high porosity and interconnectivity to promote bone ingrowth and vascularisation.
- Ability to degrade at a controlled rate that matches the rate of new bone formation.
- Ability to allow easy handling and sterilisation.
- Constitutes a crystalline material (hence excluding silicate-based bioactive glasses and glass-ceramics).
- Constitutes a monophasic material with a single identifiable crystalline phase.
- Contains a dopant which is (1) an element incorporated for ionic substitution of calcium; (2) a metal oxide incorporated into the xCaO–ySiO2 structure; or (3) a combination of both strategies.
- Has been tested for biocompatibility or bioactivity through at least one in vitro or in vivo experiment.
2. Synthesis of DCSCs
3. Mechanical Properties of Solid and Porous DCSCs
Influence of Fabrication Method on the Mechanical Properties of DCSC Scaffolds
4. Degradation and Ion Release Characteristics of DCSCs
5. Radiopacity of DCSCs
6. In Vitro Cell Interactions with DCSCs
7. In Vivo Performance of DCSCs
8. Development of DCSCs for Broader Clinical Applications
8.1. DCSC-Inorganic Composites
8.2. Polymer-DCSC Composites
8.3. Coating of DCSC Scaffolds
8.4. DCSC-Coated Metal Implants
9. Conclusions and Future Perspectives
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Ceramic | Stoichiometric Formula | Fabrication Method and Heat Treatment | Ref. |
---|---|---|---|
α-calcium silicate (α-CS) (pseudowollastonite) | CaO–SiO2 | Chemical precipitation, sintered at 1250 °C for 3 h | [27] |
β-calcium silicate (β-CS) | CaO–SiO2 | Chemical precipitation, sintered at 1100 °C for 3 h Chemical precipitation, sintered at 1090 °C for 2 h | [27] [30] |
Sr-α-CaSiO3 (Sr-α-CS) | xSrO–(1 − x)CaO–SiO2; x = 0.01~0.10 | Chemical precipitation, sintered at 1250 °C for 3 h | [31] |
Sr-β-CaSiO3 (Sr-β-CS) | xSrO–(1 − x)CaO–SiO2; x = 0.10 | Chemical precipitation, sintered at 1090 °C for 2 h | [30] |
Cu-β-CaSiO3 (Cu-CS) | xCuO–(1 − x)CaO–SiO2; x = 0.025 | Chemical precipitation, calcined at 900 °C for 2 h | [32] |
Akermanite (AK) | 2CaO–MgO–2SiO2 | Sol-gel, sintered at 1370 °C for 6 h | [37] |
Co-Akermanite (Co-AK) | 2CaO–CoO–2SiO2 | Sol-gel, sintered at 1200 °C for 3 h | [42] |
Diopside (DS) | CaO–MgO–2SiO2 | Co-precipitation, sintered at 1300 °C for 2 h | [36] |
Bredigite (BD) | 7CaO–4SiO2–MgO | Sol-gel, sintered at 1350 °C for 8 h | [38] |
Hardystonite (HT) | 2CaO–ZnO–2SiO2 | Sol-gel, sintered at 1350 °C for 5 h Sol-gel, sintered at 1250 °C for 3 h | [39] [25] |
Sr-hardystonite (Sr-HT) | xSrO–(2 − x)CaO–ZnO–2SiO2; x = 0.10 | Sol-gel, sintered at 1250 °C for 3 h | [25] |
Sphene (Sph) | CaO–TiO2–SiO2 | Sol-gel, sintered at 1280 °C, time not reported | [40] |
Baghdadite (Bag) | 3CaO–ZrO2–2SiO2 | Sol-gel, sintered at 1400 °C for 3 h Solid-state sintering at 1400 °C for 3 h | [33] [51] |
Sr-Bag (Sr-Bag) | xSrO–(3 − x)CaO–ZrO2–2SiO2, x = 0.1, 0.75 | Solid-state sintering at 1400 °C for 3 h | [41] |
Cuprorivaite (Cup) | CaO–CuO–4SiO2 | Sol-gel, calcined at 1000 °C | [35] |
Gehlenite (GLN) | 2CaO–Al2O3–SiO2 | Solid-state sintering at 1400 °C for 3 h | [34] |
Ceramic | Porosity (%) | Young’s Modulus (GPa) | Mechanical Strength (MPa) | Fracture Toughness (MPa·m1/2) | Ref. |
---|---|---|---|---|---|
α-calcium silicate | 15.5 | NR | 39.7B | NR | [27] |
82.2PSST | ~0.012 | 0.3C | NR | [29] | |
~89PSST | NR | 0.03C | NR | [28] | |
β-calcium silicate | 18.6 | NR | 65.9B | NR | [27] |
Sr-α-CaSiO3 | No mechanical property evaluation | ||||
Sr-β-CaSiO3 | No mechanical property evaluation | ||||
Cu-β-CaSiO3 | No mechanical property evaluation | ||||
Akermanite | 10.4 | 42 | 176.2B | 1.83 | [68] |
63.5PSST 81.7PSST 90.3PSST | NR | 1.13C 0.79C 0.53C | NR | [69] | |
57.9SLS | NR | 5.9C | 1.72 | [63] | |
53DIW | ~0.5 | 71C | NR | [64] | |
Co-akermanite | No mechanical property evaluation | ||||
Diopside | NR (dense) | 170 | 300B | 3.5 | [52] |
75PSST 82PSST | 0.07 0.01 | 1.4C 0.5C | NR | [70] | |
Bredigite | 5.8 ~90PSST | 43 NR | 156B 0.233C | 1.57 NR | [38] |
Hardystonite | 17.4 | NR | 136.4B | 1.24 | [39] |
77.5PSST | NR | 1.99 ± 0.45C | NR | [25] | |
~89PSST | NR | 0.06 | NR | [28] | |
74DIW | NR | 1.6 ± 0.3C | NR | [65] | |
Sr-hardystonite | 78PSST | NR | 2.16 ± 0.52C | NR | [25] |
Sphene | No mechanical property evaluation | ||||
Baghdadite | 0.5 | 120 | 98B | 1.3 | [51] |
2.8 | NR | 168B | 1.2 | [41] | |
~88PSST | ~0.0153 | ~0.27C | NR | [71] | |
Sr-Baghdadite | 3.4 | NR | 162B | 1.3 | [41] |
Cuprorivaite | No mechanical property evaluation | ||||
Gehlenite | 0.3 | 112 | 162B; 403C | 2.7 | [34] |
Bioglass 45S5 | Dense | 35 | 42 | NR | [72] |
Bioglass 45S5-derived scaffold | 86–94 | NR | 0.3–1.2B; 0.05–0.45C | NR | [73] |
Hydroxyapatite (HA) | NR (dense) | 47 | 110B | 1.1 | [52] |
<0.8 | 80–110 | 100–160B; 500C | 1.0 | [72] | |
2.2–7.0 | 87–97 | 84–113B | 0.69–0.96 | [74] | |
β-Tricalcium phosphate (β-TCP) | <0.3 | 33–90 | 140–154B; 460–687C | NR | [72] |
0.6~1.4 | 87–95 | 118–133B | 1.14–1.30 | [74] | |
Biphasic calcium phosphate (BCP) | ~88PSST | 0.0105 | 0.12C | NR | [71] |
Cortical bone | 5–13 | 12–18 | 50–150B; 130–180C | 2–12 | [7,13,17] |
Cancellous bone | 30–90 | 0.1–0.5 | 10–20B; 4–12C | 0.1–0.8 | [7,13,17] |
Ceramic | Morphology and Concentration | Surrounding Aqueous Media | Weight Loss after 7 Days, (α-CS Value) | pH of Media after 7 Days, (α-CS Value) | Apatite Formation in SBF | Total ion Release in Media after 7 Days unless otherwise stated, (α-CS Value) | Ref. |
---|---|---|---|---|---|---|---|
β-calcium silicate | Solid disks, ratio of disk to media not reported | CM | NR | NR | Yes | Ca: ~160 ppm, (~120 ppm) | [84] |
Si: ~90 ppm, (~80 ppm) | |||||||
Sr-α-CaSiO3 | Solid disks, at 0.1 cm2/mL | SBF | 5% at 2.5 mol Sr, (7%) | 8.3, (8.4) | Yes | Ca: ~260 ppm, (~310 ppm) | [31] |
Si: ~65 ppm, (~98 ppm) | |||||||
Sr: ~2.6 ppm | |||||||
7% at 10 mol Sr, (7%) | 8.0, (8.4) | Yes | Ca: ~260 ppm, (~310 ppm) | [31] | |||
Si: ~85 ppm, (~85 ppm) | |||||||
Sr: ~7.9 ppm | |||||||
Sr-β-CaSiO3 | No degradation evaluation of sintered disks/scaffolds | ||||||
Cu-β-CaSiO3 | No degradation evaluation of sintered disks/scaffolds | ||||||
Akermanite | Solid disks, at 0.1 cm2/mL | SBF | NR | 7.3 | Yes | Ca: ~240 ppm | [37] |
Si: ~62 ppm | |||||||
Mg: ~121 ppm | |||||||
Solid disks, at 0.15 mm3/mL | Tris-HCl | 2.50% | NR | Yes | NR | [36] | |
Solid disks in 48-well plate | CM | NR | NR | Ca: ~95 ppm | [36] | ||
Si: ~26 ppm | |||||||
Mg: ~30 ppm | |||||||
Solid disks, 10 mm diameter in 1 mL solution | CM | NR | NR | Ca: ~100 ppm | [85] | ||
Si: ~100 ppm | |||||||
Mg: ~195 ppm | |||||||
Porous scaffolds at 5 mg/mL | Ringer’s solution | 7% | NR | Yes | Cannot deduce concentration as volume of samples was not reported | [69] | |
Co-akermanite | No degradation evaluation of sintered disks/scaffolds | ||||||
Diopside | Solid disks, at 0.15 mm3/mL | Tris-HCl | 0.50% | NR | Yes | NR | [36] |
Solid disks in 48-well plate | CM | NR | NR | Ca: ~87 ppm | [36] | ||
Si: ~70 ppm | |||||||
Mg: ~20 ppm | |||||||
Porous scaffolds at 5 mg/mL | SBF | 1.00% | 7.5 | Yes | Si: ~150 ppm | [70] | |
Bredigite | Solid disks, at 0.15 mm3/mL | Tris-HCl | 5% | NR | Yes | NR | [36] |
Solid disks in 48-well plate | CM | NR | NR | Ca: ~70 ppm | [36] | ||
Si: ~32 ppm | |||||||
Mg: ~20 ppm | |||||||
Hardystonite | Solid disks, at 0.1 cm2/mL | SBF | NR | 7.5 | No | Ca: ~100 ppm14 days, (~600 ppm) | [81] |
Si: ~33 ppm14 days, (~75 ppm) | |||||||
Zn: ~0.4 ppm14 days | |||||||
Porous scaffolds at 5 mg/mL | SBF | 0.7%, (8%) | 7.2, (8.6) | No | Ca: ~16 ppm, (340 ppm) | [25] | |
Si: ~6 ppm, (98 ppm) | |||||||
Zn: ~0.004 ppm | |||||||
Porous scaffolds (7 × 7 × 7 mm3) in 15 mL | Tris-HCl | ~3%, (~11%) | 7.5, (8.2) | NR | Ca: 22 ppm, (144 ppm) | [28] | |
Si: 5 ppm, (19 ppm) | |||||||
Zn: 1 ppm | |||||||
Sr-hardystonite | Porous scaffolds at 5 mg/mL | SBF | 1.2%, (8%) | 7.7, (8.6) | Yes | Ca: ~40 ppm, (340 ppm) | [25] |
Si: ~11 ppm, (98 ppm) | |||||||
Zn: ~0.0005 ppm | |||||||
Sr: ~0.6 ppm | |||||||
Sphene | Solid disks, at 0.1 cm2/mL | SBF | ~0%, (7%) | ~7.7, (~8.4) | No | Ca: ~20 ppm, (~310 ppm) | [40] |
Si: 0 ppm, (~98 ppm) | |||||||
Ti: 0 ppm | |||||||
Baghdadite | Solid disks, ratio of disk to media not reported | CM | NR | 7.5, (8.1) | Yes | Ca: ~370 ppm, (~384 ppm) | [33] |
Si: ~44 ppm, (~49 ppm) | |||||||
Zr: 0 ppm | |||||||
Porous scaffolds, 150 mg/L | SBF | 9% | 8 | Yes | Ca: ~200 ppm | [71] | |
Si: ~32 ppm | |||||||
Zr: 0.0005 ppm | |||||||
Sr-Baghdadite | No degradation evaluation of sintered disks/scaffolds | ||||||
Cuprorivaite | No degradation evaluation of sintered disks/scaffolds | ||||||
Gehlenite | Solid disks, at 0.1 mm2/mL | SBF | ~0% | ~7.4 | No | Ca: ~45 ppm9 days, SBF | [34] |
Tris-HCl | ~1% | ~7.4 | Si: ~5 ppm9 days, SBF | ||||
Citric acid | ~7% | ~4 | Al: ~10 ppm9 days, SBF |
Ceramic | XMAC at 20 keV (Dense Material) |
---|---|
Cortical bone | 4.00 |
Bioglass 45S5 | 4.09 |
Diopside | 4.27 |
Gehlenite | 5.31 |
Akermanite | 5.36 |
α-, β-CaSiO3 | 5.94 |
Hydroxyapatite | 6.38 |
Tricalcium phosphate | 6.49 |
Bredigite | 6.62 |
Sphene | 7.53 |
Cu-β-CaSiO3 (2.5 mol % substitution of Ca) | 9.26 |
Cuprorivaite | 9.54 |
Sr-α-, β- CaSiO3 (10 mol % substitution of Ca) | 9.90 |
Co-akermanite | 9.91 |
Hardystonite | 12.96 |
Sr-hardystonite (5 mol % substitution of Ca) | 13.61 |
Baghdadite | 20.76 |
Sr-Baghdadite (25 mol % substitution of Ca) | 21.74 |
Ceramic | Cell Type | Ceramic Morphology | Main Findings | Ref. |
---|---|---|---|---|
Sr-α-CaSiO3 (Sr-α-CS) | Human bone-derived cells | Powder ionic extract | Sr ions in Sr-α-CS extract enhanced cell proliferation at lower Ca and Si concentrations, compared to α-CS extracts with no Sr | [31] |
Sr-β-CaSiO3 (Sr-β-CS) | Ovariectomised rat bone marrow-derived stem cells | Powder ionic extract | Enhanced cell proliferation, ALP activity, and osteogenic gene expression (Runx2, BSP, OC, VEGF, OPG/RANKL ratio) in Sr-β-CS extract (6.25 mg/mL) compared to β-CS extract | [30] |
Human umbilical vein endothelial cells | Powder ionic extract | Enhanced cell proliferation, angiogenic gene expression (VEGF, KDR), and in vitro angiogenesis in Sr-β-CS extract (3.1~12.5 mg/mL) compared to β-CS extract | [30] | |
Cu-β-CaSiO3 (Cu-β-CS) | Human umbilical vein endothelial cells | Powder ionic extract | No difference in cell proliferation between β-CS and Cu-β-CS extracts; enhanced angiogenic gene expression (VEGF, KDR, HIF-1α) and in vitro angiogenesis in Sr-β-CS extract (3.1~12.5 mg/mL) compared to β-CS extract | [32] |
Akermanite (AK) | Human bone marrow-derived stromal cells | Powder ionic extract | Enhanced proliferation, ALP activity, and osteogenic gene expression (OC, OPN) in AK extract (0.78 mg/mL) compared to β-TCP control | [98] |
Human bone marrow-derived stromal cells | Direct seeding on dense ceramic disks | Enhanced proliferation, ALP activity, and osteogenic gene expression (ALP, BSP, OPN) on AK disk compared to β-TCP control | [99] | |
Calf bone marrow stromal cells | Direct seeding on porous scaffold | Cells attached on AK scaffold; no significant difference in cell proliferation and ALP activity on AK scaffold compared to tissue culture plastic | [69] | |
Human periodontal ligament cells | Direct seeding on dense ceramic disks | Enhanced attachment, proliferation, and osteogenic gene expression (OPN, DMP-1, OC) on AK disk compared to β-TCP control | [85] | |
Human adipose-derived stem cells | Powder ionic extract | Slight inhibition of proliferation at high AK extract concentrations (25~100 mg/mL) compared to no AK extract control; significantly enhanced ALP activity, mineralisation, and OCN synthesis of cells in AK extract (25~50 mg/mL) compared to no extract control; enhanced osteogenic gene expression (Cbfα1, ALP, OCN), but reduced Col1 expression compared to no extract control; ERK pathway implicated in stimulation of osteogenic differentiation | [94] | |
Human induced pluripotent stem cells | Powder ionic extract | AK extracts had no cytotoxic effects or effects on cell stemness; enhanced ALP activity, mineralisation, and osteogenic gene expression (ALP, BMP-2, Col1, OCN, Runx2) compared to culture medium without AK extract, with optimal extract concentration at 1.56 mg/mL | [97] | |
Rat bone marrow-derived stem cells | Powder ionic extract | Enhanced proliferation, ALP activity, osteogenic (Runx2, BMP-2, BSP, OPN, OC, OPG/RANKL) and angiogenic (VEGF, ANG-1) gene expression, and inhibited TNF-α expression of cells in AK extract (12.5 mg/mL) compared to β-TCP control; activated ERK, P38, AKT and STAT3 pathways | [100] | |
Rat bone marrow macrophages | Powder ionic extract | Inhibited mature osteoclast formation and osteoclastogenesis (TRAP, cathepsin K, NFATcl) compared to β-TCP control | [100] | |
Human bone marrow-derived mesenchymal stem cells | Powder ionic extract | Enhanced cell proliferation (at 0.78–3.1 mg/mL), ALP activity, and osteogenic gene expression (OPN, Col1) compared to β-TCP extract | [101] | |
Human aortic endothelial cells | Powder ionic extract | Enhanced cell proliferation, nitric oxide synthesis, angiogenic gene expression (eNOs, KDR, FGFR1, ACVRL1), and in vitro angiogenesis in AK extract (3.1~12.5 mg/mL) compared to β-TCP extract and ceramic-free control | [101] | |
Co-akermanite (Co-AK) | Mouse osteoblast-like cells (MC3T3-E1) | Powder ionic extract | Inhibited cell proliferation in Co-AK extract (6.25–200 mg/mL); enhanced ALP activity in Co-AK extract of 0.78 mg/mL compared to β-CS | [42] |
Human umbilical vein endothelial cells | Powder ionic extract | Inhibited cell proliferation in Co-AK extract (50–200 mg/mL); enhanced angiogenic gene expression (VEGF, eNOs) and in vitro angiogenesis in Co-AK extract of 0.78 mg/mL compared to β-CS | [42] | |
Diopside (DS) | Human periodontal ligament cells and human bone marrow-derived mesenchymal stem cells | Powder ionic extract | Enhanced proliferation of hPDLCs at 100–200 mg/mL compared to β-TCP and hardystonite; enhanced OCN expression of hBMSCs at 50 mg/mL | [95] |
Human bone marrow derived-mesenchymal stem cells | Powder ionic extract | Enhanced cell proliferation (at 1.6 mg/mL), ALP activity, and osteogenic gene expression (OPN) compared to β-TCP extract | [101] | |
Human aortic endothelial cells | Powder ionic extract | No significant difference in cell proliferation, nitric oxide synthesis, angiogenic gene expression (eNOs, KDR, FGFR1, ACVRL1), and in vitro angiogenesis compared to β-TCP extract and ceramic-free control | [101] | |
Bredigite (BD) | Human bone marrow-derived mesenchymal stem cells | Powder ionic extract | Enhanced cell proliferation (at 0.39–3.1 mg/mL), ALP activity, and osteogenic gene expression (OPN, Col1) compared to β-TCP extract | [101] |
Human aortic endothelial cells | Powder ionic extract | Enhanced cell proliferation, nitric oxide synthesis, angiogenic gene expression (eNOs, KDR, FGFR1, ACVRL1), and in vitro angiogenesis in BD extract (3.1~12.5 mg/mL) compared to β-TCP extract and ceramic-free control | [101] | |
Human periodontal ligament cells | Powder ionic extract | Enhanced cell proliferation at 6.25–25 mg/mL compared to tissue culture plastic; enhanced ALP activity and osteogenic gene expression (ALP, OC, OPN, BSP, CAP, CEMP1) at 50 mg/mL compared to tissue culture plastic; shown to activate Wnt/β-catenin signalling pathway | [96] | |
Hardystonite (HT) | Human osteoblast-like cells | Direct seeding on dense ceramic disks | Cells adhered; significantly enhanced cell proliferation and ALP activity of cells on HT disks compared to α-CS | [81] |
Human bone marrow derived mesenchymal stem cells | Direct seeding on dense ceramic disks; indirect co-culture of cells and ceramic disk | Enhanced proliferation in indirect culture compared to β-TCP and tissue culture plastic, while proliferation rate was lower for direct seeding; higher ALP activity on HT compared to β-TCP; significantly higher osteogenic expression (Col1, ALP, OPN, BSP, OC) compared to β-TCP for direct seeding | [102] | |
Human periodontal ligament cells and human bone marrow-derived mesenchymal stem cells | Powder ionic extract | Enhanced ALP expression of hBMSCs at 12.5 mg/mL compared to diopside and β-TCP; enhanced antibacterial effect against E. faecalis compared to β-TCP, comparable antibacterial effect with calcium hydroxide | [95] | |
Primary human osteoblasts | Direct seeding on porous ceramic scaffolds | Enhanced cell attachment and BSP gene expression for cells seeded on HT compared to calcium silicate, while all other osteogenic genes tested (Runx2, OPN, OC, Col1, ALP) showed insignificant difference or reduced expression compared to calcium silicate | [28] | |
Primary human osteoblasts | Direct seeding on porous ceramic scaffolds | Enhanced cell proliferation and ALP activity on HT scaffolds compared to β-TCP, and enhanced OPN gene expression compared to tissue culture plastic | [25] | |
Sr-hardystonite (Sr-HT) | Primary human osteoblasts | Direct seeding on porous ceramic scaffolds | Enhanced osteogenic gene expression (OC, BSP, OPN, Runx2) on Sr-HT scaffolds compared to hardystonite scaffolds and tissue culture plastic | [25] |
Sphene (Sph) | Primary human bone-derived cells | Direct seeding on dense ceramic disks | Cells adhered; significantly enhanced cell proliferation and ALP activity of cells on hardystonite disks compared to α-CS | [40] |
Baghdadite (Bag) | Primary human osteoblasts | Direct seeding on dense ceramic disks | Enhanced proliferation, ALP activity, and osteogenic expression (Col1, ALP, BSP, OC, RANKL, OPG) on Bag disks compared to α-CS | [33] |
Primary human monocytes | Direct seeding on dense ceramic disks | Bag disks supported osteoclast differentiation from monocytes as opposed to α-CS | [33] | |
Human dermal microvascular endothelial cells | Direct seeding on dense ceramic disks | Bag disks supported endothelial cell attachment and enhanced expression of VE-cadherin as opposed to α-CS | [33] | |
Primary human ostoblasts; adipose-derived stem cells | Direct seeding on dense ceramic disks; indirect co-culture | Bag disks showed enhanced osteogenic expression in HOBs (Runx2, BSP, OPN, OC) and ASCs (Runx2, OPN); Bag shown to modulate cross-talk between HOBs and ASCs via BMP-2 pathway | [103] | |
Unactivated macrophages derived from primary human monocytes | Direct seeding on porous scaffold; indirect co-culture | Bag disks promoted upregulation of genes related to pro-remodelling M2c phenotype | [108] | |
Human periodontal ligament cells | Direct seeding on dense ceramic disks; powdered extract | Enhanced ALP activity, upregulated cementogenic and osteogenic gene expression, and upregulated Wnt/β-catenin pathway-related genes compared to β-TCP for both direct and indirect culture methods | [109] | |
Human osteoblasts | Direct seeding on dense ceramic disks | Enhanced attachment, proliferation, and ALP expression of cells on Bag disks compared to α-CS | [41] | |
Sr-Baghdadite (Sr-Bag) | Human osteoblasts | Direct seeding on dense ceramic disks | Enhanced attachment, proliferation, and ALP expression of cells on Sr-baghdadite disks compared to α-CS, with optimal ALP expression at 0.7 mol % Sr substitution of calcium | [41] |
Cuprorivaite (Cup) | Mouse osteoblast-like cells (MC3T3-E1) | Powder ionic extract | Cytotoxic at 25–200 mg/mL; inhibited ALP activity of cells cultured in 0.195–0.78 mg/mL Cup extract compared to β-CS | [35] |
Human umbilical vein endothelial cells | Powder ionic extract | Cytotoxic at 25–200 mg/mL; enhanced in vitro angiogenesis and VEGF expression of cells cultured in 0.39–0.78 mg/mL Cup extract compared to β-CS extract and copper extract; has antibacterial effects against E. coli | [35] | |
Gehlenite (GLN) | Primary human osteoblasts | Direct seeding on dense ceramic disks | Enhanced cell attachment, proliferation, and osteogenic gene expression (Runx2, OPN, BSP, OC) on GLN disks compared to biphasic calcium phosphate disks | [34] |
Mouse bone marrow macrophages | Direct seeding on dense ceramic disks | Promoted formation of TRAP-positive osteoclasts, and enhanced osteoclast attachment and polarisation | [34] |
Ceramic | Implant Morphology | Animal Model | Implantation Period | Main Findings | Ref. |
---|---|---|---|---|---|
Sr-β-CaSiO3 (Sr-β-CS) | Porous scaffolds | Ovariectomised rat calvarial defects | 4 weeks | µ-CT analysis showed higher bone mineral density, trabecular thickness, and bone volume/total volume ratio for Sr-β-CS compared to β-CS; histomorphometric analysis showed higher new bone area, blood vessel area, and faster in vivo degradation for Sr-β-CS compared to β-CS | [30] |
Akermanite (AK) | Porous scaffolds | Rabbit femoral defects | 8 and 16 weeks | Fluorescence labelling showed no significant difference in mineral apposition rate of new bone formation between AK and β-TCP scaffolds; histomorphometric analysis showed slightly higher new bone formation, and faster in vivo degradation of AK scaffolds compared to β-TCP | [98] |
Porous scaffolds | Ovariectomised rat calvarial defects | 2, 4, 6 and 8 weeks | µ-CT analysis showed higher trabecular thickness and bone volume/total volume ratio in AK scaffolds compared to β-TCP; polychrome sequential fluorescent labelling showed enhanced new bone growth and mineral apposition in AK scaffolds compared to β-TCP; histomorphometric assay showed higher new bone area and blood vessel area in AK scaffolds compared to β-TCP | [100] | |
Diopside (DP) | Dense specimens | Rabbit jaw bone defects | 12 weeks | Direct, gradient bonding between native bone and DP implant | [52] |
Dense spheres (1–1.5 mm diameter) | Rat femoral defects | 2 and 4 weeks | Histological analysis showed new bone growth which formed tissue bridges with DP spheres, slightly higher bone regeneration score compared to β-TCP, and evidence of dynamic endochondral ossification; quantitative analysis on histology sections showed higher Col1 expression and similar OPN expression compared to β-TCP | [111] | |
Hardystonite (HT) | Porous scaffolds | Rat tibial defects | 3 and 6 weeks | HT scaffolds showed new bone formation inside scaffold pores in both the external cortex and internal medullary cavity, in comparison to only external cortex for β-TCP control at both 3 and 6 weeks; limited in vivo resorption and limited ALP activity compared to β-TCP | [25] |
Sr-hardystonite (Sr-HT) | Porous scaffolds | Rat tibial defects | 3 and 6 weeks | Sr-HT scaffolds showed new bone formation inside scaffold pores in both the external cortex and internal medullary cavity, in comparison to only external cortex for β-TCP control at both 3 and 6 weeks; limited in vivo resorption but extensive ALP activity compared to hardystonite and β-TCP | [25] |
Baghdadite (Bag) | Dense 1–1.5 mm diameter spheres | Rat femoral defects | 2 and 4 weeks | Histological analysis showed new bone growth which formed tissue bridges with Bag spheres, significantly higher bone regeneration score compared to β-TCP, and evidence of dynamic endochondral ossification with increased amount of regularly arranged woven bone compared to diopside and β-TCP; significantly higher Col1 expression and OPN expression compared to diopside and β-TCP scaffolds | [111] |
Porous scaffolds | Rabbit radial segmental defects | 12 weeks | Radiographic analysis showed enhanced defect bridging for Bag scaffolds compared to BCP scaffold; histological analysis showed enhanced bone ingrowth into pores of Bag scaffold compared to mostly peripheral bone growth for BCP scaffold; histomorphometric analysis showed increased new bone formation in Bag scaffolds (3.0 ± 3.1 mm2) compared to BCP (1.3 ± 1.0 mm2) at the scaffold midpoint; observed evidence of osteoclast-mediated resorption | [71] | |
Porous scaffolds | Sheep tibial segmental defects | Up to 26 weeks | Radiographic analysis showed clinical union at the bone-scaffold interface in all samples after 26 weeks; biomechanical analysis showed that torsional strength of the implant and associated bone reached ~10% of contralateral intact tibia; histological analysis showed average 80% bridging of the defect length in all samples, as well as new bone growth inside the scaffold pores | [110] |
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No, Y.J.; Li, J.J.; Zreiqat, H. Doped Calcium Silicate Ceramics: A New Class of Candidates for Synthetic Bone Substitutes. Materials 2017, 10, 153. https://doi.org/10.3390/ma10020153
No YJ, Li JJ, Zreiqat H. Doped Calcium Silicate Ceramics: A New Class of Candidates for Synthetic Bone Substitutes. Materials. 2017; 10(2):153. https://doi.org/10.3390/ma10020153
Chicago/Turabian StyleNo, Young Jung, Jiao Jiao Li, and Hala Zreiqat. 2017. "Doped Calcium Silicate Ceramics: A New Class of Candidates for Synthetic Bone Substitutes" Materials 10, no. 2: 153. https://doi.org/10.3390/ma10020153
APA StyleNo, Y. J., Li, J. J., & Zreiqat, H. (2017). Doped Calcium Silicate Ceramics: A New Class of Candidates for Synthetic Bone Substitutes. Materials, 10(2), 153. https://doi.org/10.3390/ma10020153