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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