Table 3.
Articles included and details of each investigation.
| References | Aims | MBG Composition | MBG Compared with Conventional BG? | MBG Elabos Method | Type of Cells Used | Culture Setting (Direct or Indirect Contact) | Techniques Used to Assess Biocompatibility | Main Results |
|---|---|---|---|---|---|---|---|---|
| Lin—2015 [49] | Bone regeneration | MBG (no information on the composition of the MBG) + polyglycerol sebacate (adjuvant) | No Blank control |
Sol-gel | rBMSCs: rat bone marrow mesenchymal stem cells | Direct | Cell adhesion: Optical density Cell morphology: CLSM Cell viability: MTT assay Cell differentiation: ALP activity assay and qRT-PCR analysis (RUNX-2, OCN, OPN) |
Same viability and morphology. Adhesion and proliferation increased with PGS concentration. At high concentrations, biocompatibility decreased due to acidification. |
| Min—2015 [50] | Bone regeneration | MPHS: MBG 80S15C (80SiO2: 15CaO: 5P2O5) + PHBHHx (adjuvant) | No Negative control (without treatment) |
3D printing | hBMSCs: human bone marrow mesenchymal stem cells | Direct | Cell adhesion: SEM Cell viability: CCK-8 assay Cell differentiation: ALP activity assay and qRT-PCR analysis (OCN, OPN, bFGF, SDF-1) |
Cell morphology: well-extended MPHS-1.0 and MPHS-1.5 with a higher DMOG enhanced cell % rate Higher ALP activity, expression levels of OCN and OPN than MPHS scaffolds. |
| Gómez-Cerezo—2016 [51] | Bone regeneration | MBG 58S (58 SiO2: 37 CaO: 5 P2O5) + polycapro-lactone (adjuvant) | No Polycaprolactone alone |
Sol-gel | MC3T3-E1: murine osteoblastic cells | Direct | Cell morphology: SEM & CLSM Cell viability: Alamar Blue assay and membrane integrity: LDH: CytoTox-ONE ™ (Promega, G7890) Cell differentiation: ALP activity assay |
MBG stimulated cell proliferation, colonization, and differentiation. Cell migration affected by architectural features and enhanced by the chemical release produced during the MBG dissolution. |
| Han—2016 [52] | Bone regeneration | MBG (no information on the composition of the MBG) + PMMA (adjuvant), titanium-doped | No Negative control: no titanium |
Sol-gel | U2OS: human osteosarcoma cell line | Direct | Cell viability: MTT assay | Slight cytotoxicity for all titanium concentrations. No effect on the cell proliferation. |
| Hesaraki—2016 [53] | Bone regeneration | MBG 64S (64SiO2: 31CaO: 5P2O5) + resin poly-methacrylate (adjuvant) | No Resin alone |
Sol-gel | Calvarium-derived newborn rat osteoblasts | Direct | Cell morphology: SEM Cell viability: MTT assay |
Bioactive glass/resin composite biocompatible and osteoconductive. |
| Kim—2016 [54] | Bone regeneration | MBG 85S (85SiO2: 15CaO) functionalized with amino groups | No Blank control |
Sol-gel | RAW264.7: murine macrophages | Direct | Cell morphology: CLSM Cell viability: CCK-8 assay Cell differentiation: qRT-PCR analysis (c-fos, cathepsin-K, TRAP, NFATc1) |
Cell viability dose and time dependent. Morphological characteristics reflected results of cell viability. |
| Pourshahrestani—2016 [55] | Hemostasis | Ga-MBGs: MBG 80S15C (80SiO2: 15CaO: 5P2O5) doped with gallium Si/Ca/P/Ga: 80/15/5/0; 79/15/5/1; 78/15/5/2; 77/15/5/3 |
No Control: MBG without gallium |
Sol-gel | HDFs: human dermal fibroblast cells | Indirect | Cell viability: MTT assay | All glasses were non-cytotoxic. Cell viability enhanced in the presence of 1% Ga-MBGs. |
| Singh—2016 [56] | Bone regeneration and drug delivery | MBG (no information on the composition of the MBG) doped C-dot | No Blank control |
Sol-gel | HeLa cell line, MC3T3-E1 murine osteoblastic cells, rBMSCs: rat bone marrow mesenchymal stem cells | Direct | Cell viability: MTT assay and CCK-8 assay | High bioactivity in vitro and cell viability of the developed nanospheres, equivalent to the bioactive glass nanoparticles. |
| Tang—2016 [57] | Bone regeneration | TMS/rhBMP-2, TMS (trimodal MBG scaffold), MBG with different pore sizes (macro/micro/nano-porous) (no information on the composition of the MBG) |
No Blank control |
Sol-gel | rBMSCs: rat bone marrow mesenchymal stem cells and HUVECs: human umbilical vein endothelial cells | Direct | Cell morphology: CLSM & SEM Cell adhesion: CLSM Cell viability: LIVE/DEAD assay Cell differentiation: ALP activity assay and qRT-PCR analysis (RUNX-2, OCN, OPN, BSP, GAPDH) |
Excellent cytocompatibility with all trimodal and bimodal scaffolds and desirable environment for cells attachment and colonization. |
| Vishnu Priya—2016 [58] | Bone regeneration | Hydrogel containing magnesium-doped bioglass (60SiO2: 30CaO:10MgO) | No Control: hydrogel without MBG |
Sol-gel | HUVECs: human umbilical vein endothelial cells and ADSCs: rabbit adipose-derived stem cells | Direct | Cell proliferation: Alamar Blue Cell adhesion: Fluorescence microscopy Cell differentiation: ALP activity, immunofluorescence (ALP, OCN) |
Hydrogels containing MBG showed early initiation of differentiation and higher expression of ALP and osteocalcin confirming the osteoinductive property of MBG. |
| Wang—2016 [20] | Bone regeneration | MBG 80S15C (80SiO2: 15CaO: 5P2O5) doped with copper Si/Ca/P/Cu: 78/15/5/2; 75/15/5/5 |
No Control: TCPS |
Sol-gel | MC3T3: mouse fibroblast cells | Direct and indirect | Cell adhesion: SEM Cell viability: MTT assay and CLSM Cell differentiation: qRT-PCR analysis (VEGF, bFGF and PDGF) |
Cytotoxicity of copper dose dependent. Copper: proangiogenic (promotes differentiation) |
| Wu—2016 [59] | Bone regeneration and osteoporosis | MBG 80S15C (80 SiO2:15CaO) | No Blank control |
Sol-gel | rBMSCs: bone marrow mesenchymal stem cells derived from either sham control or ovariectomized (OVX) rats | Indirect | Cell proliferation: CCK-8 assay Cell morphology and cytoskeletal structure: fluorescence microscopy Cell differentiation: ALP staining, Alizarin Red S, Oil Red-O staining, qRT-PCR (RUNX2, PPARγ, GAPDH), western blot (WB) (Runx2, PPARγ, β-actin) |
Lower concentration of MBG dissolution can promote osteogenesis but inhibit adipogenesis of the sham and OVX BMSCs. |
| Zhang—2016 [60] | Bone regeneration | Large-pore MBG (no information on the composition of the MBG) | No Blank control |
Not indicated | ADSCs: rat adipose-derived stem cells | Direct | Cell morphology: SEM Cell viability: MTS assay Cell differentiation: qRT-PCR analysis (ALP, OCN, OPG, PPAR gamma) |
Proliferation related to ions released. Large pore mesoporous glass promotes the expression of osteogenic-related genes but also inhibit the expression of adipogenic genes. |
| Zhang—2016 [61] | Bone regeneration | MBG 80S15C (80SiO2: 15CaO: 5P2O5) functionalized with amino groups | No Blank control |
Sol-gel | Rabbit BMSCs: bone marrow mesenchymal stem cells | Direct | Cell adhesion: SEM Cell viability: MTT assay Cell differentiation: ALP activity assay & qRT-PCR analysis (ALP, BSP, OCN, RUNX-2) |
Amino-MBGS: the most potent proliferative effect and the most effective osteoblastic differentiation potential. |
| Ge—2017 [62] | Bone regeneration | MBG on nanoTitanium film, doped with growth factor. Special composition related to doping: SiO2/CaO/P2O5/TiO2: 80/5/5/10 |
No Control without the drug |
Sol-gel | rBMSCs: rat bone marrow mesenchymal stem cells | Direct | Cell differentiation: ALP activity assay and qRT-PCR analysis (COL-1, OCN) | Highest ALP activity and strong Col-I and OCN expressions on 200-MBG film cells: possibly, due to the surface of the glass that accelerates the signal transduction. |
| Kaur—2017 [63] | Bone regeneration | MBG 64S (64 SiO2: 31 CaO: 5 P2O5) doped with copper (2.5 to 10%) | No Blank control |
Sol-gel | J774A.1: murine macrophage cell line | Direct | Cell viability: MTT assay and Membrane integrity: Trypan Blue assay | High concentrations of copper (from 1,95 µg/mL): toxic. With the decrease in concentration, all the MBGs increased live cell and decreased dead cell rates. |
| Li—2017 [64] | Gene delivery | MBG (no information on the composition of the MBG) + polyglycerol + Arg8 (to functionalize polymer), loaded with DNA | No Blank control |
Sol-gel | Human HeLa cervical cancer cell line | Direct | Cell viability: LIVE/DEAD assay and CCK-8 assay | Good cell biocompatibility. Most cells in the complex-treated groups grew well in contact with the MBG/DOX-treated group. |
| Luo—2017 [65] | Bone regeneration | Nanofibrous MBG (no information on the composition of the MBG) | No Blank control |
Sol-gel | Mouse osteoblasts | Direct | Cell morphology: SEM & Fluorescence microscopy Cell viability: LIVE/DEAD assay and CCK-8 assay Cell differentiation: ALP activity assay |
60S40C scaffolds: favorable support for cell growth, proliferation, and differentiation. |
| Luo—2017 [66] | Bone regeneration | NanoMBG 58S (58 SiO2: 37 CaO: 5 P2O5) | No Blank control |
Aerogel-based method | Primary mouse osteoblast cells | Direct | Cell morphology: Fluorescence microscopy Cell adhesion: Fluorescence microscopy Cell viability: CCK-8 assay Cell differentiation: ALP activity assay |
58S scaffold: more cells growth and cell differentiation than scaffold without 58S. |
| Pourshahrestani—2017 [67] | Hemostasis | MBG 80S15C (80SiO2: 15CaO: 5P2O5) doped with gallium (Ga) + chitosan (CHT = adjuvant) Si/Ca/P/Ga: 79/15/5/1 Ga-MBG/CHT (wt.%): 10/90; 30/70; 50/50 |
No Negative control: chitosan alone |
Sol-gel | HDFs: human dermal fibroblast cells | Direct | Cell viability: Alamar Blue assay and LIVE/DEAD assay Cell morphology: CLSM |
Good biocompatibility. No cytotoxicity. |
| Qi—2017 [68] | Bone regeneration | MBG 80S (80SiO2: 16CaO: 4P2O5) + calcium sulfate hydrate (adjuvant) | No Control: calcium sulfate hydrate alone |
3D printing | hBMSCs: human bone marrow mesenchymal stem cells | Direct | Cell adhesion: SEM Cell viability: CCK-8 assay Cell differentiation: ALP activity assay and qRT-PCR analysis (ALP, OCN, OPN, RUNX-2) |
Cell viability, proliferation, and differentiation increased with increase MBG concentrations. |
| Sánchez-Salcedo—2017 [69] | Bone regeneration | MBG 75S (75SiO2: 20CaO: 5P2O5) & MBG 85S (85SiO2: 15CaO) both functionalized with amino groups or lysine |
No Blank control |
Sol-gel | MC3T3-E1: mouse osteoblastic cells | Direct | Cell morphology: Inverted optical microscopy Cell adhesion: Fluorescence microscopy Cell viability: MTS assay and membrane integrity: LDH: CytoTox-ONE ™ (Promega, G7890) Cell differentiation: ALP activity assay |
In vitro cytocompatibility of MBGs was preserved functionalization. |
| Schumacher—2017 [70] | Bone regeneration and drug delivery | MBG 80S (80SiO2: 16CaO: 4P2O5) + CaP bone cement (calcium phosphate cement) (adjuvant) | No Control: calcium phosphate cement alone |
Sol-gel | Saos2: human osteosarcoma cell line | Direct | Cell viability: WST-1 | Higher cell adhesion and metabolic activity for composites compared to pure calcium cement. |
| Shoaib—2017 [71] | Bone regeneration | MBG (49SiO2: 20CaO: 20Na2O: 7K2O: 4P2O5 mol %) doped with potassium | Yes Control: Bioglass 45S5 |
Sol-gel | NHFB: normal human fibroblast cell line | Direct | Cell viability: CCK-8 assay Cell-cycle analysis: Flow cytometer Cell differentiation: ELISA (anti-OCN) and ALP activity assay |
Cell viability: no differences. Cell-cycle analysis: MBG did not have any role in cell cycle dose-dependency. |
| Wang—2017 [72] | Bone regeneration | MBG (no information on the composition of the MBG) functionalized with amino groups | No Control: conventional MBG |
Sol-gel | MC3T3-E1: mouse osteoblast cell line | Direct | Cell adhesion: CLSM Cell viability: CCK-8 assay Cell differentiation: ALP activity assay, Luciferase assay (RUNX-2) and qRT-PCR analysis (GAPDH, OCN, OPN) |
Better cell adhesion with amino-MBGs than with conventional MBGs. Both MBGs with or without adjuvant promote osteoblastic differentiation. |
| Xin—2017 [73] | Bone regeneration | Nano MBG80S (80SiO2: 16CaO: 4P2O5) (MBGN) + methacrylicanhydride and gelatin (GelMA-G) (adjuvants) | No Blank control |
Not indicated | MC3T3-E1: mouse osteoblast cell line | Direct and indirect | Cell adhesion: SEM Cell viability: CCK-8 assay Cell differentiation: ALP activity assay |
GelMA-G-MBGN membrane enhanced osteogenesis differentiation. |
| Xue—2017 [74] | Bone regeneration | NanoMBG (NanoBGs) (No information on the composition of the MBG) loaded with miRNA (adjuvant) | No Blank control |
Sol-gel | hBMSCs: human bone marrow mesenchymal stem cells | Direct | Cell morphology: Inverted fluorescent microscopy Cell adhesion: Inverted fluorescent microscopy Cell viability: Alamar Blue assay and LIVE/DEAD assay Cell differentiation: qRT-PCR analysis (ALP, OPN, RUNX2) |
Good cell biocompatibility. NanoBGs could efficiently deliver miRNA to enhance osteogenic differentiation. |
| Yu—2017 [75] | Gene delivery | MBG 80S (80SiO2: 16CaO: 4P2O5) and silica nanoparticles | No Control: commercial transfection reagent PEI 25K and LIPO300 |
Sol-gel | hBMSCs: human bone marrow mesenchymal stem cells | Direct | Cell viability: LIVE/DEAD assay Cell differentiation: ALP activity assay |
NanoBGs revealed significantly lower cytotoxicity than the commercial transfection reagents. |
| Cai—2018 [76] | Bone regeneration | MBG (no information on the composition of the MBG) + trapped BMP2 (adjuvant) + microspheres of chitosan (adjuvant) (containing IL8) | No Blank control |
Sol-gel | rBMSCs: rat bone marrow mesenchymal stem cells | Direct | Cell viability: CCK-8 assay Cell differentiation: ALP activity assay and qRT-PCR analysis (RUNX-2, COL-1, OPN, OCN, β-actin) |
Below 1 mg/mL, microspheres exhibited little cytotoxicity to rBMSCs. |
| Covarrubias—2018 [77] | Bone regeneration | NanoMBG (nBGs) (No information on the composition of the MBG) + chitosan/gelatin (CHT/Gel 1:1) (adjuvant) | Yes nMBG/CHT/Gel, and nBG/CHT/Gel bionano-composite scaffolds | Sol-gel | DPSCs: dental pulp stem cells | Direct | Cell viability: MTS assay Cell differentiation: ALP activity assay |
Cell viability and proliferation decreased with the concentration of nBGs (due to high calcium release); 5% nBGs allowed the highest cell proliferation rate. |
| Fiorilli—2018 [78] | Bone regeneration | MBG 85S (85SiO2: 15CaO) doped with strontium | No Control: polystyrene |
Sol-gel and aerosol-spray drying method | J774a.1, fibroblast cell line L929, Saos-2 | Direct and indirect | Cell viability: MTT assay Cell differentiation: qRT PCR analysis (ALP, COL-1, GAPDH, OPG, RANKL, SPARC) |
Good biocompatibility: reduction of the inflammatory response and stimulation of the pro-osteogenic genes’ expression. |
| Gómez-Cerezo—2018 [79] | Bone regeneration | MBG 75S (75SiO2: 20CaO: 5P2O5) | No Control: without material Then, different doses of MBG-75S (0.5 mg/mL, 1 mg/mL, 2 mg/mL) |
Sol-gel | Human Saos-2, osteoclast-like cells, murine RAW 264.7 murine macrophages | Direct | Cell morphology: CLSM Cell viability: Membrane integrity: LDH: CytoTox-ONE ™ (Promega, G7890) Apoptosis quantification and cell-cycle analysis: Flow cytometry |
Cytotoxicity is dose dependent. No inhibition of osteoclastogenesis. Decrease of resorption activity. |
| Hsu—2018 [80] | Bone regeneration | Apatite-modified MBG (no information on the composition of the MBG): MBGNFs (MBG nanofibers) with PMMA and sodium alginate (adjuvants) | No | Sol-gel | MG-63: human osteoblast-like | Direct | Cell morphology: Fluorescence microscopy Cell differentiation: Immunofluorescence (BSP and OCN) |
Better cell adhesion but lower viability with macroporous microbeads containing MBG nanofibers than with glass beads. |
| Jia—2019 [81] | Osteoporosis | Sr-MBG (Porous strontium- incorporated mesopore- bioglass) MBG doped with 5% Sr |
No Control: MBG 80S 80Si02:15CaO:5 P2O5 |
Sol-gel | hPDLc: human periodontal ligament stem cells | Indirect | Cell differentiation: Remineralization (Alizarin Red staining and quantification), WB (hnRNPL, Setd2, H3K36me3, P-AKT, AKT, P-CREB) and RT qPCR analysis (hnRNPL, Setd2, ALPL, RUNX-2, GAPDH) |
Sr-MBG scaffolds had visibly more new bone formation and vascular distribution in the healing area than MBG scaffolds. More frequent RUNX-2-positive cells were detected in the presence of Sr while the percentage of hnRNPL-positive cells was less in Sr-MBG group. |
| Kumar—2019 [82] | Bone regeneration | MBG 64S (64SiO2: 31CaO: 5P2O5) + surfactant | No No control at all |
Sol-gel | Human Saos-2: Sarcoma osteogenic cells | Direct | Cell viability: Membrane integrity: LDH: CytoTox-ONE ™ (Promega, G7890) | Cell proliferation was significantly affected by the textural characteristics, which is related to dissolution rate of Ca, P, and Si. |
| Mandakhbayar–2019 [83] | Bone regeneration | Sr-doped (85SiO2:10CaO:5SrO) and Sr-free (85SiO2:15CaO) nanobioactive glasses | No Blank control |
Sol-gel | DPSCs: dental pulp stem cells | Indirect | Cell cytotoxicity: WST-1, CCK-8 assay and CLSM Cell differentiation: ALP activity and Alizarin Red staining and quantification” |
Sr-NBC: high bioactivity, excellent biodegradability, fast therapeutic ion release, and high drug loading capability, which potentiates its application in dentin−pulp complex regeneration therapy. |
| Pourshahrestani—2018 [84] | Hemostasis | Gallium-doped MBG (no information on the composition of the MBG) | No Control: other hemostatic reagents |
Sol-gel | HDFs: human dermal fibroblast cells | Direct | Cell viability: MTT assay and LIVE/DEAD assay | No toxic effect. Significant increase of viability. |
| Qi—2018 [85] | Bone regeneration | 3D printed borosilicate BG (6Na2O, 8K2O, 2MgO, 6SrO, 22CaO, 36B2O3, 18SiO2, 2P2O5; mol.%) coated with MBG (no information on the composition of the MBG) | Yes BG coated with MBG compared with BG without coating |
3D printing | hBMSCs: human bone marrow mesenchymal stem cells | Direct | Cell adhesion: SEM Cell viability: CCK-8 assay Cell differentiation: ALP activity assay and qRT-PCR analysis (RUNX-2, OCN, COL1) |
Well-spread cell morphology. Proliferation rates of BG-MBG > BG scaffolds (P < 0.05). ALP activity: BG-MBG > BG (P < 0.05). Upregulation of osteogenic-related genes in cells grown on BG-MBG (P < 0.05). |
| Shoaib—2018 [86] | Drug delivery | MBG doped with potassium (special composition related to doping: 49SiO2: 20CaO: 20Na2O: 7K2O: 4P2O5 mol %) with variable percentages was used as filler in arginine and starch-based PU matrices (adjuvant) | No Different percentages of MBG in the nanocomposite |
Sol-gel | NHFB: normal human fibroblast cell line | Direct | Cell viability: MTT assay | Enhancement of cell adhesion. No significant difference on cell viability. |
| Zeng—2018 [87] | Bone regeneration | MBG 80S (80SiO2: 16CaO: 4P2O5) functionalized with amino groups (N-MBG) | No Blank control |
Not indicated | Rabbit BMSCs: bone marrow mesenchymal stem cells | Direct and indirect | Cell viability: LIVE/DEAD assay and MTT assay Cell differentiation: ALP activity assay and qRT-PCR analysis (CaSR, RUNX-2, GAPDH, OPG, RANKL, IL-10, Arg-1) |
Better cell viability and differentiation with N-MBG. Decreased gene expression after NPS2143 (CaSR signaling pathway inhibitor) treatment. |
| Du—2019 [88] | Bone regeneration | MBG (no information on the composition of the MBG) + silk fibroin (adjuvant) (MBG/SF) | No Control: MBG/PCL scaffold |
Sol-gel | hBMSCs: human bone marrow mesenchymal stem cells | Direct | Cell adhesion: SEM and CLSM Cell viability: CCK-8 assay Cell differentiation: ALP activity assay and qRT-PCR analysis (BMP-2, OCN, OPN, BSP, COL-1) |
Better cell adhesion and proliferation on MBG/SF composite scaffold. |
| Fu—2019 [89] | Drug delivery | MBG (no information on the composition of the MBG) + sodium alginate (SA) (adjuvant) | No SA alone |
3D printing | hBMSCs: human bone marrow mesenchymal stem cells | Direct | Cell adhesion: CLSM Cell viability: CCK-8 assay Cell differentiation: ALP activity assay and qRT-PCR analysis (OCN, COL-1, BMP-2, BSP) |
More live cells, better cell proliferation and differentiation were observed on MBG/SA and MBG/SA–SA scaffolds compared to SA scaffolds. |
| Gómez-Cerezo—2019 [90] | Osteoporosis, bone regeneration and drug delivery | MBG58S (58 SiO2: 37 CaO: 5 P2O5) + e-polycapro-lactone (adjuvant) | No Blank control |
Sol-gel | Human Saos-2 osteoblasts, RAW-264.7 murine macrophages | Direct and indirect | Cell morphology: CLSM Apoptosis quantification: Flow cytometer Cell-cycle analysis: Flow cytometer |
Zoledronic acid released from MBG produced osteoblast apoptosis and a delay of osteoblast proliferation in a time-dependent way; caused an inflammation and fibrosis. |
| Li—2019 [91] | Bone regeneration and drug delivery | Scaffold PLGA- MBG (SiO2-CaO-P2O5, Si/Ca/P=80:15:5) and FTY/MBG-PLGA FTY (adjuvant) | No Control: PLGA without MBG |
Sol-gel | rBMSCs: rat bone marrow mesenchymal stem cells and HUVECs: human umbilical vein endothelial cells | Indirect | Cell adhesion: Immunofluorescence Cell proliferation: CCK-8 assay Cell-cycle analysis: WB (Erk1/2, p-Erk1/2) Cell differentiation: ALP activity assay, Alizarin Red S, crystal violet, immunofluorescence (OCN), qRT-PCR analysis (β-actin, ALP, OCN, BMP-2, Osterix, Hif-1α, VEGF-A, CXCR4), WB (Hif-1α and β-actin) |
The scaffolds exhibited sustained release of the bioactive lipids as well as the calcium and silicon ions, which were demonstrated to broadly enhance biological activities including the adhesion, proliferation, and osteogenic differentiation of rBMSCs as well as the proliferative and in vitro angiogenic ability of HUVECs. |
| Liu—2019 [92] | Bone regeneration | MBG (no information on the composition of the MBG)-hydroxyapatite + silk fibroin (adjuvant) | No Silk fibroin alone |
Sol-gel | hMSCs: human mesenchymal stem cells | Direct | Cell morphology: FESEM (field emission scanning electron microscopy) Cell viability: MTT assay Cell differentiation: ALP activity assay and qRT-PCR analysis (COL-1, OCN, RUNX-2, GAPDH) |
Positive osteogenic differentiation effect and upregulated osteoblastic gene expression of samples containing a high concentration of hydroxyapatite. |
| Montalbano—2019 [93] | Bone regeneration | NanoMBG_Sr4% (dopant) + Type I collagen (adjuvant), with 4-StarPEG crosslinked special composition of MBG related to doping (Sr/Ca/Si = 4/11/85 %mol) | No Control: TCPS and non-crosslinked biomaterial samples |
Sol-gel | MG-63 human osteoblast-like | Direct and indirect | Cell adhesion: SEM Cell viability: Alamar Blue assay and indirect cytotoxicity assay using “conditioned medium” |
Good cell adhesion, morphology, and viability. |
| Pourshahrestani—2019 [94] | Bone regeneration | AgMBG/POC: silver-doped MBG 80S15C (80SiO2: 15CaO: 5P2O5) + poly (1,8 octanediol citrate) (adjuvant) Si/Ca/P/Ag: 79/15/5/1: 1%AgMBG AgMBG/POC (wt.%): 5/95; 10/90; 20/80 |
No Control: adjuvant alone |
Sol-gel | HDFs: human dermal fibroblast cells | Direct | Cell viability: Alamar Blue assay | Efficient antibacterial properties while preserving a favorable biocompatibility. |
| Terzopoulou—2019 [95] | Bone regeneration | MBG 80S (80SiO2: 16CaO: 4P2O5) doped with calcium or strontium + polycapro-lactone (PCL) (adjuvant) | No Blank control |
Sol-gel | WJ-MSCs: human Wharton’s jelly-derived mesenchymal stem cells | Indirect | Cell adhesion: Fluorescence microscopy Cell viability: MTT assay |
No cytotoxicity observed after 24 h. Osteoinductive additives in PCL matrices facilitate the differentiation. |
| Varini—2019 [96] | Bone regeneration | Cerium-doped (0 to 5%) MBG 80S (80SiO2: 16CaO: 4P2O5) + sodium alginate (adjuvant) | No Blank control |
Sol-gel | MC3T3-E1: mouse osteoblastic cells | Direct and indirect | Cell viability: Alamar Blue assay and membrane integrity: LDH: CytoTox-ONE ™ (Promega, G7890) Cell differentiation: ALP activity assay |
Better proliferation. No release of cytotoxic agent. Differentiation decreased with the amount of cerium. |
| Wang—2019 [17] | Bone regeneration | MBG and MBG-L (larger pores) (no information on the composition of the MBG), FGF (fibroblast growth factor) adsorbed (adjuvant) | No Control: simple MBG |
Sol-gel | MC3T3-E1: mouse osteoblast cell line | Direct | Cell adhesion: laser microscope Cell viability: CCK-8 assay Cell differentiation: ALP activity assay, Luciferase assay (RUNX-2) and qRT-PCR analysis (RUNX-2, OCN, OPN, GAPDH) |
Better cell adhesion, proliferation, differentiation with large-pore MBG. Adding FGF enhanced the cell adhesion and differentiation even more. |
| Wang—2019 [97] | Bone regeneration | MBG80S15C (80SiO2: 15CaO: 5P2O5) + GO (graphene oxide) (adjuvant) | No Control: MBG alone |
Sol-gel | rBMSCs: rat bone marrow mesenchymal stem cells | Direct and indirect | Cell morphology: SEM Cell adhesion: SEM Cell viability: CCK-8 assay Cell differentiation: ALP activity assay, RT-qPCR analysis (RUNX-2, ALP, OCN, COL-1, VEGF, HIF-1α) and immunofluorescence (OCN) |
Better cell proliferation and differentiation with the MBG containing an adjuvant. |
| Wu—2019 [98] | Bone regeneration in osteoporosis | MBG 80S (80SiO2: 16CaO: 4P2O5) + sodium alginate (SA) + gelatin (G); soaked with calcitonin gene-related peptide (CGRP) or Naringin (NG) (adjuvants) | No Control: MBG and MBG/SA/G |
Sol-gel | MG-63: human osteoblast-like | Direct and indirect | Cell adhesion: Inverted fluorescent microscopy and SEM Cell viability: CCK-8 assay Cell differentiation: qRT-PCR analysis (RUNX-2, ALP, OPN, OCN) |
No difference in adhesion. Drug adjuvants enhanced proliferation and differentiation. |
| Zhang—2019 [99] | Bone regeneration | MBG (no information on the composition of the MBG) | No Blank control |
Not indicated | rBMSCs: rat bone marrow mesenchymal stem cells | Direct | Cell morphology: SEM and TEM Cell proliferation: Immunofluorescence (Ki67) Cell differentiation: WB (ALP, RUNX-2, OCN, BMP-2, β-actin, Gli1, Smo), qRT-PCR analysis (ALP, RUNX-2, OCN, BMP-2, Gli1, Smo) and RNA |
Bioactive glass–ceramic coating promoted proliferation and differentiation, and up regulated the expression of osteogenesis-related genes. |
| Zheng—2019 [100] | Bone regeneration, drug delivery | Cu-MBGNs: MBG 85S (85SiO2: 15CaO) doped with copper (0 to 10%) | No Blank control |
Sol-gel | Mesenchymal stromal ST2 cells derived from mouse bone marrow of BC8 mice | Indirect | Cell viability: CCK-8 assay | Cytotoxicity of Cu-MBGNs was related to the concentration of Cu ions as well as the dosage of particles applied. |
| Berkmann—2020 [101] | Bone regeneration | MBG 85S(85SiO2: 15CaO) | No Blank control |
Aerosol spray-drying method | hMSCs: human mesenchymal stem cells | Indirect | Cell viability: PrestoBlue, LDH Cell counting: DAPI test. Cell differentiation: Alizarin-Red staining |
Ionic dissolution products amplify the osteogenic differentiation of hMSCs. |
| Chitra—2020 [102] | Bone regeneration | MBG 45S5 (45SiO2: 24.5CaO: 24.5Na2O: 6P2O5): crystalline phase: Na2Ca2Si3O9 and Na2Ca3Si6O16 | Yes | Sol-gel | MG-63: human osteoblast-like and PBMC: human peripheral blood mononuclear cell | Direct | Cell viability: MTT assay | The probe sonication enriches the biocompatibility. |
| Mocquot—2020 [21] | Bone regeneration | MBG 75S(75SiO2: 15CaO: 10P2O5) | No Blank control |
Sol-gel | hDPCs: human dental pulp cells | Indirect | Cell morphology: CLSM Cell viability: Alamar Blue assay Cytotoxicity: crystal violet test Cell differentiation: ALP activity assay and immunofluorescence (OCN and DMP-1) |
The MBG showed no cytotoxicity, good cytoskeletal architecture, cell spreading and adhesion. |
| Montalbano—2020 [103] | Osteoporosis | Nano MBG (85% SiO2: 11% CaO + 4% Sr) + collagen (adjuvant) | No Blank control |
Sol-gel | MG-63: human osteoblast-like + SaOS-2: human osteosarcoma cell line | Direct | Cell viability: Alamar Blue assay Cell adhesion and morphology: SEM |
The developed hybrid system largely proved its biocompatibility in presence of MG-63 and Saos-2 cells. |
| Montes-Casado—2020 [104] | Immunity | NanoMBG (81.44% SiO2- 18.6% CaO) |
No Control: cells without NanoMBGs |
Sol-gel | Murine BMDCs: Bone marrow-derived dendritic cells + SR.D10 Th2 CD4+ lymphocytes + DC2.4 dendritic cells | Direct | Cell differentiation: Flow cytometry assays (FACS + antigenic markers) Cell inflammation: cytokine expression: immunofluorescence (FACS + cytokine markers) Cell proliferation: CellTraceTM Violet dye (FACS) Apoptosis: Annexin V (FACS) Cytotoxicity: CLSM |
NanoMBGs were both non-toxic and non-inflammagenic for murine lymphoid cells and myeloid DCs despite their efficient intake by the cells. |
| Pontremoli—2020 [105] | Bon regeneration | Zwitterionic or no zwitterionic Nano (_SG) and micro (_SD) particles of MBG_Sr2% (85SiO2:13CaO:2Sr) | No Control: cells without MBGs |
Sol-gel | MC3T3-E1: mouse osteoblast cell line | Direct | Cell proliferation: MMT-test Cytotoxicity: LDH Cell differentiation: Alizarin Red staining and quantification Cell adhesion: SPS-PAGE and Coomassie blue for visualization |
After zwitterionization the in vitro bioactivity was maintained, no cytotoxicity about Sr-MBG particles. Zwitterionic Sr-MBGs showed a significant reduction of adhesion. |
| Wang—2020 [106] | Bone regeneration | Large-pore MBG (no information on the composition of the MBG) + genistein (adjuvant) | No Control: MBG with normal pore size |
Sol-gel | MC3T3-E1: mouse osteoblast cell line | Direct | Cell adhesion: Fluorescence microscopy Cell viability: CCK-8 assay Cell differentiation: ALP activity assay and qRT-PCR analysis (OPN, GAPDH) |
Genistein is a molecule good for cell attachment. MBG-L/G is the better substrate for osteoblast differentiation. |
| Zhou—2020 [107] | Bone regeneration | MBG/SIS-P28: MBG (no information on the composition of the MBG) doped with SIS (porcine small intestinal submucosa) + BMP2-related peptide P28 MBG/SIS-H-P28 (heparinized MBG/SIS) |
No Control: MBG/SIS |
Sol-gel | MC3T3-E1: mouse osteoblast cell line | Direct | Cell proliferation: MTT-test Cell viability: CLSM Cell differentiation: ALP activity, Alizarin Red staining) and qRT-PCR analysis (GAPDH, RUNX-2, OCN, OPN, ALP) |
MBG/SIS-H-P28 scaffolds exhibit a much stronger ability to stimulate bone regeneration. |
| Zhou—2021 [108] | Bone regeneration | MBGNs (no information on the composition of the mesoporous bioactive glass nanoparticles) | No Control: gelatin (Gel)/oxidized chondroitin sulfate (OCS) hydrogel without MBGN + different MBGN concentrations (0%, 5%, 10% and 15%) |
Sol-gel | rBMSCs: rat bone marrow mesenchymal stem cells | Direct | Cell adhesion and spreading: CLSM Cell proliferation: CCK-8 assay Cell viability: LIVE/DEAD assay Cell differentiation: Immunostaining (RUNX-2), ALP activity assay, qRT-PCR analysis (OCN, RUNX-2, OPN, COL-1), WB (OCN, OPN), Immunofluorescence (OPN) and Alizarin Red staining |
Presence of MBGNs enhanced proliferation of BMSCs and osteogenic differentiation of BMSCs grown on Gel/OCS/MBGN hydrogel surfaces. |
Abbreviations: PGS (poly(glycerol sebacate); PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)); DMOG (dimethyloxallyl glycine); LDH (lactate dehydrogenase); PMMA (poly(methyl methacrylate); TRAP (tartrate-resistant acid phosphatase), NFATc1 (nuclear factor of activated T-cells cytoplasmic 1); C-dot (carbon dot); rhBMP-2 (recombinant human bone morphogenetic protein-2); TCPS (tissue culture polystyrene); VEGF (vascular endothelial growth factor); PDGF (Platelet Derived Growth Factor); PPAR-gamma (peroxisome proliferator-activated receptor gamma); Arg8 (octoarginine); DOX (doxorubicin); RANKL (receptor activator of nuclear factor kappa-Β ligand); SPARC (secreted protein, acidic, cysteine-rich); hnRNPL (heterogeneous nuclear ribonucleoprotein L); Setd2 (SET domain containing 2); P-AKT (phosphorylated Akt); Akt (protein kinase B); P-CREB (phospho-cAMP response element-binding protein); PU (polyurethanes); CaSR (calcium-sensing receptor); BMP-2 (bone morphogenetic protein-2); PLGA (particle-poly (lactic-co-glycolic acid); FTY (Fingolimod); Erk1/2 (extracellular signal-regulated kinase 1/2); p-Erk1/2 (phospho-Erk1/2); 4-StarPEG (4-star poly(ethylene glycol) ether tetrasuccinimidyl glutarate); HIF-1α (hypoxia-inducible factor-1α); Hh (hedgehog); Gli1 (glioma-associated oncogene); Smo (smoothened); DMP-1 (dentin matrix acidic phosphoprotein 1); FACS (fluorescence-activated cell sorting for flow cytometry).