Table 5.
Summary of in vitro studies on DCSCs performed using a range of cell types and material morphologies (powder extracts, dense disks and porous scaffolds).
| 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] |
CS: calcium silicate; β-TCP: β-tricalcium phosphate; ALP: alkaline phosphatase; BSP: bone sialoprotein; Col1: collagen type I; OC: osteocalcin; OPN: osteopontin; VEGF: vascular endothelial growth factor; OPG: osteoprotegerin; RANKL: receptor activator of nuclear factor kappa-B ligand; HIF: hypoxia inducible factor; DMP: dentin matrix acidic phosphoprotein; TNF: tumour necrosis factor; ANG: angiopoietin; BMP: bone morphogenetic protein; TRAP: tartrate-resistant acid phosphatase; eNOS: endothelial nitric oxide synthase; FGFR1: fibroblast growth factor receptor 1; ACVRL1: activin A receptor like type 1; CAP: catabolite activator protein; CEMP1: cementum protein 1; hPDLCs: human periodontal ligament cells; hBMSCs: human bone marrow-derived mesenchymal stem cells; ASCs: adipose-derived stem cells; HOBs: human osteoblast-like cells.