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Table 1 Results of in vitro studies

From: The impact of Zn-doped synthetic polymer materials on bone regeneration: a systematic review

Author/year Control group Experimental group Zn content Cell type Cell proliferation and viability assessment Cell osteogenic differentiation assessment Results
Oh et al. 2012 [16] PLDLA membrane a. PLDLA membrane combined with bioactive glasses (BG, 70SiO2-30CaO), fixed at ~ 7/3 by weight
b. PLDLA membrane combined with ZnBG (70SiO2-25CaO-5ZnO), fixed at ~ 7/3 by weight
5.41 wt% in ZnBG; 1.62 wt% in the PLDLA-ZnBG membrane rBMSCs MTS assay ALP activity/immunofluorescence staining for BSP/cellular mineralization No statistical significance was noted in the cell viability assay (p > 0.05); the PLDLA-ZnBG group showed the best results in promoting cell osteogenic differentiation and cellular mineralization
Amiri et al. 2016 [17] Tissue culture polystyrene (TCPs) a. PES-PEG scaffold, fixed at 7/3 ratio by weight
b. Zn2SiO4-PES-PEG scaffold (PES-PEG scaffold immersed in the ethanol solution containing 1 wt% Zn2SiO4)
0.59 wt% in the coating hMSCs MTT assay ALP activity/RT-PCR assay/immunofluorescence staining for osteocalcin and osteopontin/calcium content assay/Alizarin Red S (ARS) staining Higher values of hMSC proliferation rate for Zn2SiO4-PES-PEG compared to PES-PEG fibrous scaffolds and TCPs; Zn2SiO4-PES-PEG scaffolds showed the best results in promoting cell osteogenic differentiation and calcium deposition
Bejarano et al. 2016 [18] Neat PDLLA scaffold a. PLA/10-BG (60SiO2-25CaO-11Na2O-4P2O5; 10 wt% of BG) scaffold
b. PLA/30-BG (30 wt% of BG) scaffold
c. PLA/10-1CuBG (BG doped with 1 mol% of CuO) scaffold
d. PLA/30-1CuBG scaffold
e. PLA/10-1ZnBG (BG doped with 1 mol% of ZnO) scaffold
f. PLA/30-1ZnBG scaffold
g. PLA/10-1Cu1ZnBG (BG doped with 1 mol% of CuO and 1 mol% of ZnO) scaffold
h. PLA/30-1Cu1ZnBG scaffold
0.11 wt% in PLA/10-1ZnBG and PLA/10-1Cu1ZnBG; 0.32 wt% in PLA/30-1ZnBG and PLA/30-1Cu1ZnBG; ST-2 cells CCK-8 assay ALP activity Neat PDLLA scaffolds and scaffolds with 10 wt% of BG showed high cell viability, and the scaffolds with 30 wt% of the zinc-doped BG did not generate significant cytotoxicity; compared to other groups, the PLA/30-1ZnBG scaffold showed the highest ALP activity values
Deng et al. 2018 [19] Porous sulfonated PEEK (SPEEK) disk a. Ag-SPEEK disk (SPEEK disk immersed in Ag+ solution)
b. Zn-SPEEK disk (SPEEK disk immersed in Zn2+ solution)
c. Ag/Zn-SPEEK disk
18.51 wt% in the coating Human osteoblast-like MG-63 cells CCK-8 assay ALP activity/RT-PCR assay Zn-containing SPEEK significantly promoted cell proliferation in the initial phase at low zinc concentration; the Ag/Zn-SPEEK surface had the best effect of promoting differentiation of MG-63 cells
Rajzer et al. 2019 [20] Pure PCL membrane a. PCL-A2 (BG: 40SiO2-54CaO-6P2O5, 4 wt%) membrane
b. PCL-A2Zn5 (BG: 49CaO-5ZnO-6P2O5-40SiO2, 4 wt%) membrane
5.08 wt% in A2Zn5; 0.2 wt% in PCL-A2Zn5 Human osteoblasts cells   ALP activity/bioactivity was evaluated by examining the formation of apatite layer in simulated body fluid (SBF) BG doped with Zn favors ALP expression in comparison with pure PCL membrane; the surface of PCL-A2 membranes showed the most apatite formation in SBF
Telgerd et al. 2019 [21] Tissue culture plate (TCP) a. PLLA nanofiber scaffold
b. Zn-Cu-imidazole metal-organic framework (MOF)-coated PLLA scaffold (PLLA@MOF)
9.1 wt% in the coating Human adipose tissue-derived mesenchymal stem cells MTT assay ALP activity/calcium content assay PLLA@MOF showed good biocompatibility and provided favorable adhesion and proliferation of cells; PLLA@MOF showed the highest ALP activity and calcium deposition
Li et al. 2019 [22] Poly (amino acids) scaffold (PAA) a. PAA-0.025M scaffold (PAA powder dispersed into 0.025 mol/L zinc chloride solutions)
b. PAA-0.05M scaffold (PAA powder dispersed into 0.05 mol/L zinc chloride solutions)
c. PAA-0.1M scaffold (PAA powder dispersed into 0.1 mol/L zinc chloride solutions)
No specific content in the final scaffolds BMSCs CCK-8 assay ALP activity/Alizarin Red S staining PAA-0.025M and PAA-0.05M promoted cell proliferation, while PAA-0.1M exhibited cytotoxicity; the highest ALP activity and calcium nodules were found with PAA-0.05M
Neto et al. 2019 [23] Biphasic calcium phosphate (BCP) scaffold coated with PCL/PDLA/PEA/PEU a. BCP-6Sr scaffold (BCP doped with 6 mol% Sr2+)
b. BCP-6Sr2Mg scaffold (BCP-6Sr doped with 2 mol% Mg2+)
c. BCP-6Sr2Zn scaffold (BCP-6Sr doped with 2 mol% Zn2+)
d. BCP-6Sr2Mg2Zn scaffold (BCP-6Sr doped with 2 mol% Mg2+ and 2 mol% Zn2+)
*All the scaffolds were coated with PCL/PDLA/PEA/PEU
0.8 mol% in BCP-6Sr2Zn scaffold; 0.68 mol% in BCP-6Sr2Mg2Zn scaffold    Biomineralization capacity was analyzed by immersing the scaffolds in SBF All the composite scaffolds exhibited calcium phosphate microspheres deposition in SBF
Liang et al. 2020 [24] PLGA/CPC scaffold, fixed at 3/17 by weight a. PLGA/CPC-Si scaffold (2.6 wt% of CaSiO3)
b. PLGA/CPC-Zn scaffold (15 wt% of Zn-TCP)
c. PLGA/CPC-Si/Zn scaffold (5 wt% of Zn2SiO4)
2.6 wt% in PLGA/CPC-Zn scaffold; 2.9 wt% in PLGA/CPC-Si/Zn scaffold rBMSCs   RT-PCR assay/immunofluorescence staining for BMP-2 rBMSCs on the PLGA/CPC-Si/Zn scaffold showed the highest osteogenic differentiation effect
Kandasamy et al. 2020 [25] PCP: CMC/PVP scaffold a. PC: (Zn-Mn HAP) scaffold (Zn = Mn = 0.05 M)
b. PC1: (Zn-Mn HAP) scaffold (Zn = Mn = 0.1 M)
c. PC 20: PC/CMC/PVP scaffold (20 wt% of PC)
d. PC 40: PC/CMC/PVP scaffold (40 wt% of PC)
e. PC 60: PC/CMC/PVP scaffold (60 wt% of PC)
f. PC1–20: PC1/CMC/PVP scaffold (20 wt% of PC1)
g. PC1–40: PC1/CMC/PVP scaffold (40 wt% of PC1)
h. PC1–60: PC1/CMC/PVP scaffold (60 wt% of PC1)
No specific content in the final scaffolds Human osteoblast cells (HOS) MTT assay Formation of minerals as crystals was analyzed by immersing the scaffolds in SBF PC1–60 fiber had the highest cell proliferation and attachment values; PC1–60 were selected to perform the biomineralization activity in SBF solution; with increased soaking time, the apatite formation on the sample surface increased
  1. PLDLA poly-l-d,l-lactic acid, MTS 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium, rBMSCs rat bone marrow mesenchymal stem cells, PES polyethersulphone, PEG polyethyleneglycol, MTT 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide, hMSCs human mesenchymal stem cells, PDLLA poly (d, l-lactide), CCK-8 Cell Counting Kit-8, ST-2 bone marrow stromal cells, PEEK polyetheretherketone, OD optical density, PCL polycaprolactone, PLLA poly-l-lactic acid, PAA poly (amino acids), PDLA poly (dl-lactide), PEA poly (ester amide), PEU poly (ester urea), PLGA poly (lactic-co-glycolic acid), CPC calcium phosphate cement, CMC carboxymethyl cellulose, PVP polyvinyl pyrrolidone, HAP hydroxyapatite, Runx2 runt-related transcription factor 2, Col I collagen type 1, ALP alkaline phosphatase, OCN osteocalcin, BMP-2 bone morphogenetic protein-2