Table 2.
Synthetic hydrogels.
| Synthetic Hydrogels | |||||||
|---|---|---|---|---|---|---|---|
| Author | Hydrogel Used | Type of Study | Hydrogel Modification | Hydrogel Properties | Cells Used | Upregulated Biological Molecules | Outcomes |
| PLA Based Polymers | |||||||
| Shiehzadeh et al., 2014 [260] | Polylactic polyglycolic acid–polyethylene glycol (PLGA-PEG) | Clinical trial | Stem/progenitor cells from the apical dental papilla (SCAP) | Biologic approach can provide a favorable environment for clinical regeneration of dental and paradental tissues. | |||
| Synthetic Self-Assembling Peptide Hydrogel (Peptide Amphiphiles) | |||||||
| Galler et al., 2008 [74] | Synthetic peptide amphiphiles | In vitro | Peptide amphiphiles involves arginine–glycine–aspartic acid (RGD) and an enzyme-cleavable site | Peptide was dissolved at pH 7.0 to attain stock solution of 2% by weight | stem/progenitor cells of exfoliated deciduous teeth (SHED) and dental pulp stem cells (DPSCs) | The hydrogels are easy to handle and can be introduced into small defects, therefore this novel system might be suitable for dental tissue regeneration. | |
| Multi Domain Self-Assembling Peptide (MDP) Hydrogel | |||||||
| Galler et al., 2011 [20] | In vivo | MDP functionalized with transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2, and vascular endothelial growth factor (VEGF) via heparin binding | DPSCs | In tooth slices, implanted hydrogel degraded and replaced by a vascularized connective tissue similar to dental pulp. Pretreatment of the tooth cylinders with NoOCl showed resorption lacunae. With NaOCl followed by ethylenediaminetetraacetic acid (EDTA), DPSCs differentiated into odontoblasts-like cells intimately associated with the dentin surface. | |||
| Galler et al., 2012 [1] | MDP | In vivo | MDP functionalized with TGF-β1, FGF-2, and VEGF via heparin binding | DPSCs | Hydrogels implanted into the backs of immunocompromised mice resulted in the formation of vascularized soft connective tissue similar to dental pulp. | ||
| Colombo et al., 2020 [75] | MPD hydrogel | In vitro | SHED | Decellularized and lyophilized MDP produced a biomaterial containing anti-inflammatory bioactive molecules that can provide a tool to reduce pulpal inflammation to promote dentin–pulp complex regeneration. | |||
| RADA16-I Hydrogels Self-Assembling Peptide | |||||||
| Cavalcanti et al., 2013 [291] | A commercial self-assembling peptide | In vitro | 0.2% Puramatrix™ (1% w/v) |
DPSCs | Dentin matrix protein (DMP)-1, Dentin sialophosphoprotein (DSPP) | DPSCs expressed DMP-1 and DSPP after 21 days culturing in dentin slices containing PuramatrixTM. The surviving dentin provided signaling molecules to cells suspended in PuramatrixTM. | |
| Rosa et al., 2013 [76] | A commercial self-assembling peptide | In vitro In vivo |
0.2% Puramatrix™ (1% w/v) | SHED | DMP-I, DSPP, matrix extracellular phosphoglycoprotein (MEPE) | Upon mixing SHED with Puramatrix™ hydrogel for 7 days and injecting the construct into roots of human premolars, the cells survived and expressed (DMP-I, DSPP, MEPE) in vitro. Pulp-like tissue with odontoblasts able to form neo-dentinal tubules was observed in vivo. | |
| Dissanayaka et al., 2015 [276] | A commercial self-assembling peptide | In vitro In vivo |
Among different Puramatrix™ (1% w/v) concentrations, 0.15% was the optimal. | DPSCs and human umbilical vein endothelial cells (HUVECs) | PuramatrixTM enhanced in vitro cell survival, migration and capillary formation. Co-cultured groups on PuramatrixTM exhibited more extracellular matrix, mineralization and vascularization than DPSC-monocultures in vivo. | ||
| Nguyen et al., 2018 [88] | RADA16-I | In vitro | incorporation of dentonin sequence | Ribbonlike nanofibers with height (∼2 nm) and width (∼14 nm) | DPSCs | The self-assembled peptide platform holds promise for guided dentinogenesis. | |
| Huang, 2020 [280] | RADA16-I | In vitro | Low concentration (0.125%, 0.25%) caused higher cell proliferation rate than high concentration (0.5%, 0.75%, 1%) | DPSCs and umbilical cord mesenchymal stem cells | DSPP, DMP-1, Alkaline phosphatase (ALP), osteocalcin (OCN) | The co-culture groups promoted odontoblastic differentiation, proliferation and mineralization. | |
| Mu et al., 2020 [87] | RADA16-I | In vitro | incorporated with stem cell factor | 100 ng/mL was the optimum concentration of the stem cell factor. Nanofibers and pores diameter were (10–30nm and 5–200nm, respectively) |
DPSCs and HUVECs | Stem cell factor incorporate RADA16-I holds promise for guided pulp regeneration. | |
| Zhu et al., 2019 [142] | Cells were cultured on Matrigel before being loaded on commercial self-assembling peptide | In vitro In vivo |
300 μL 1% Puramatrix™ (1% w/v) | DPSCs overexpressing Stromal derived factor-(SDF)-1 and vascular endothelial growth factor (VEGF) | SDF-1, VEGF | Combination of VEGF- and SDF-1-overexpressing DPSCs cultured on Matrigel before being loaded on PuramatrixTM enhanced the area of vascularized dental pulp regeneration in vivo. | |
| Xia et al., 2020 [89] | Self-assembling peptide | In vitro In vivo |
incorporation of RGD, VEGF mimetic peptide sequence | The nanofibers’ diameters of functionalized peptide were thicker than pure RAD. that the stiffness of RAD/ RGD-mimicking peptide (PRG)/ VEGF-mimicking peptide: (KLT) hydrogels was greater than the others |
DPSCs and HUVECs | Modified self-assembling peptide hydrogel effectively stimulated stem cells angiogenic and odontogenic differentiation in vitro and dentin–pulp complex regeneration in vivo. | |
| Poly-dimethylsiloxane Hydrogel | |||||||
| Liu et al., 2017 [263] | Poly-dimethylsiloxane (PDMS) | In vitro | Stiffness for 10:1, 20:1, 30:1 and 40:1 was 135, 54, 16 and 1.4 kPa and roughness was 55.67, 53.38, 50.95, and from 47.32 to 42.50nm. Water contact angle was 65°. | DPSCs | osteopontin (OPN), runt-related transcription factor (RUNX)-2, Bone morphogenetic protein | Osteogenic and odontogenic markers were positively correlated to the substrate stiffness. The results revealed that the mechanical properties promoted the function of DPSCs related to the Wnt/β-catenin pathway. | |
| Poly-N-isopropylacrylamide Gel | |||||||
| Itoh et al., 2018 [267] | Poly-N-isopropylacrylamide (NIPAAm) | In vitro In vivo |
NIPAAm crosslinked by PEG-DMA | Decrease in wet weight from 1 to 0.18 at 508 C. Change in surface area from 1 (258 C) to 0.62 (508 C) within 1 h. High wettability. | DPSCs | DSPP in the outer cell layer, Nanog in the center of the constructs | DPSCs in the outer layer of the constructs differentiated into odontoblast-like cells, while DPSCs in the inner layer maintained their stemness. Pulp-like tissues rich in blood vessels were formed in vivo. |
| Polyethylene Glycol | |||||||
| Komabayashi et al., 2013 [275] | PEG | In vitro | PEG–maleate–citrate (PEGMC) (45% w/v), acrylic acid (AA) crosslinker (5% w/v), 2,2′-Azobis (2-methylpropionamidine) dihydrochloride (AAPH) photo-initiator (0.1% w/v), | Optimum cell viability with exposure time of 30 s with a monomer and AAPH concentration of 0.088% and up to 1%, respectively | L929 cells | Cell viability remained up to 80% after 6 h. Controlled Ca2+ release was attained. The viscosity and injection ability into plastic root canal blocks were confirmed in a dental model. | |
| VitroGel 3D | |||||||
| Xiao et al., 2019 [73] | Vitrogel | In vitro In vivo |
VitroGel diluted with deionized water 1:2. | SCAP | RUNX-2,DMP-1, DSPP, OCN | VitroGel 3D promoted SCAP proliferation and differentiation. SDFr-1α and BMP-2 co-treatment induced odontogenic differentiation of human SCAP cultured in the VitroGel 3D in vitro and in vivo |
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