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Mesenchymal stem cells osteogenic differentiation by ZnO nanoparticles and polyurethane bimodal foam nanocomposites

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Abstract

Mesenchymal stem cells with tissue repair capacity involve in regenerative medicine. MSCs can promote bone repair when employed with nano scaffolds/particles. Here, the MTT and Acridine Orange assay enabled the cytotoxic concentration of Zinc oxide nanoparticles and Polyurethane evaluation. Following culturing adipose tissue-derived MSCs, ADSCs' proliferation, growth, and osteogenic differentiation in the presence of PU with and without ZnO NPs is tracked by a series of biological assays, including Alkaline Phosphatase activity, Calcium deposition, alizarin red staining, RT-PCR, scanning electron microscope, and immunohistochemistry. The results showed boosted osteogenic differentiation of ADSCs in the presence of 1% PU scaffold and ZnO NPS and can thus apply as a new bone tissue engineering matrix. The expression level of Osteonectin, Osteocalcin, and Col1 increased in PU-ZnO 1% on the 7th and 14th days. There was an increase in the Runx2 gene expression on the 7th day of differentiation in PU-ZnO 1%, while it decreased on day 14th. In conclusion, Polyurethane nano scaffolds supported the MSCs’ growth and rapid osteogenic differentiation. The PU-ZnO helps not only with cellular adhesion and proliferation but also with osteogenic differentiation.

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Abbreviations

ADSCs:

Adipose tissue-derived mesenchymal stem cells

NPs:

Nanoparticles

ZnO NPs:

Zinc oxide nanoparticles

PU:

Polyurethane

PCL:

Polycaprolactone

PEMF:

Pulsed electromagnetic fields

PES-PEG:

Polyether sulfone-polyethylene glycol

TCPS:

Control tissue culture polystyrene

ALP:

Alkaline phosphatase

DLS:

Dynamic light scattering

NCO:

Isocyanate group

BDO:

1,4-Butanediol

HDI:

Hexamethylene diisocyanate

OM:

Optical microscopy

SEM:

Scanning electron microscope

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal Bovine serum

AO:

Acridine orange

EB:

Ethidium bromide

ARS:

Alizarin red S

DAPI:

4′, 6-Diamidino-2-phenylindole

FTIR:

Fourier-transform infrared spectroscopy

DSC:

Differential scanning calorimetry

References

  • Aksoy BAN, Aksoy HM, Tezel GG, Renda N, Ozkara HA, Onder E (2010) Effectiveness of topical zinc oxide application on hypertrophic scar development in rabbits. Burns 36(7):1027–1035. https://doi.org/10.1016/j.burns.2010.01.020

    Article  PubMed  Google Scholar 

  • Amiri BGM, Shahrousvand M, Kamali M, Salimi A (2016) Osteoblast differentiation of mesenchymal stem cells on modified PES-PEG electrospun fibrous composites loaded with Zn2SiO4 bioceramic nanoparticles. Differentiation 92(4):148–158

    Article  CAS  PubMed  Google Scholar 

  • Amiri B, Ghollasi M, Shahrousvand M, Kamali M, Salimi A (2016) Osteoblast differentiation of mesenchymal stem cells on modified PES-PEG electrospun fibrous composites loaded with Zn 2 SiO 4 bioceramic nanoparticles. Differentiation 92(4):148–158. https://doi.org/10.1016/j.diff.2016.08.001

    Article  CAS  PubMed  Google Scholar 

  • Arjmand M, Ardeshirylajimi A, Maghsoudi H, Azadian E (2018) Osteogenic differentiation potential of mesenchymal stem cells cultured on nanofibrous scaffold improved in the presence of pulsed electromagnetic field. J Cell Physiol 233(2):1061–1070. https://doi.org/10.1002/jcp.25962

    Article  CAS  PubMed  Google Scholar 

  • Bageshlooyafshar BVS, Kehtari M, Eslami-Arshaghi T, Rafeie F, Ramezanifard R, Rahchamani R, Mohammadi-Sangcheshmeh A, Mostafaloo Y, Seyedjafari E (2017) Zinc silicate mineral-coated scaffold improved in vitro osteogenic differentiation of equine adipose-derived mesenchymal stem cells. Res Vet Sci 16(30814–1):S0034-5288. https://doi.org/10.1016/j.rvsc.2017.09.015

    Article  CAS  Google Scholar 

  • Chen H, Zeng Y, Liu W, Zhao S, Wu J, Du Y (2013) Multifaceted applications of nanomaterials in cell engineering and therapy. Biotechnol Adv 31(5):638–653. https://doi.org/10.1016/j.biotechadv.2012.08.002

    Article  CAS  PubMed  Google Scholar 

  • Cheung H-Y, Lau K-T, Lu T-P, Hui D (2007) A critical review on polymer-based bio-engineered materials for scaffold development. Compos B Eng 38(3):291–300. https://doi.org/10.1016/j.compositesb.2006.06.014

    Article  CAS  Google Scholar 

  • Daei-Farshbaf N, Ardeshirylajimi A, Seyedjafari E, Piryaei A, Fadaei Fathabady F, Hedayati M, Salehi M, Soleimani M, Nazarian H, Moradi SL, Norouzian M (2014) Bioceramic-collagen scaffolds loaded with human adipose-tissue derived stem cells for bone tissue engineering. Mol Biol Rep 41(2):741–749. https://doi.org/10.1007/s11033-013-2913-8

    Article  CAS  PubMed  Google Scholar 

  • Dalby MJGN, Tare R, Andar A, Riehle MO, Herzyk P, Wilkinson CD, Oreffo RO (2007) The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater 6(12):977–1003

    Article  ADS  Google Scholar 

  • Dinarvand P, Hassanian SM, Qureshi SH, Manithody C, Eissenberg JC, Yang L, Rezaie AR (2014) Polyphosphate amplifies proinflammatory responses of nuclear proteins through interaction with receptor for advanced glycation end products and P2Y 1 purinergic receptor. Blood 123(6):935–945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292(5819):154–156. https://doi.org/10.1038/292154a0

    Article  ADS  CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Gorskaja JF, Kulagina NN (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 4(5):267–274

    CAS  PubMed  Google Scholar 

  • Gage FH (2000) Mammalian neural stem cells. Science 287(5457):1433–1438. https://doi.org/10.1126/science.287.5457.1433

    Article  ADS  CAS  PubMed  Google Scholar 

  • Gorna K, Gogolewski S (2003) Preparation, degradation, and calcification of biodegradable polyurethane foams for bone graft substitutes. J Biomed Mater Res A 67(3):813–827. https://doi.org/10.1002/jbm.a.10148

    Article  CAS  PubMed  Google Scholar 

  • Griffin MF, Ibrahim A, Seifalian AM, Butler PEM, Kalaskar DM, Ferretti P (2019) Argon plasma modification promotes adipose derived stem cells osteogenic and chondrogenic differentiation on nanocomposite polyurethane scaffolds; implications for skeletal tissue engineering. Mater Sci Eng C Mater Biol Appl 105:110085. https://doi.org/10.1016/j.msec.2019.110085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guelcher SA (2008) Biodegradable polyurethanes: synthesis and applications in regenerative medicine. Tissue Eng Part B Rev 14(1):3–17. https://doi.org/10.1089/teb.2007.0133

    Article  CAS  PubMed  Google Scholar 

  • Guillot PV, De Bari C, Dell’Accio F, Kurata H, Polak J, Fisk NM (2008) Comparative osteogenic transcription profiling of various fetal and adult mesenchymal stem cell sources. Differentiation 76(9):946–957

    Article  CAS  PubMed  Google Scholar 

  • Hanley CLJ, Punnoose A, Reddy KM, Coombs I, Coombs A, Feris K, Wingett D (2008) Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles. Nanotechnology 23(19):2950103

    Google Scholar 

  • Holland TA, Mikos AG (2005) Biodegradable polymeric scaffolds. Improvements in bone tissue engineering through controlled drug delivery. Tissue Eng 1:161–185

    Google Scholar 

  • Huang K, Zhu T, Nie J, Du J, Liu Y, Bao Y, Chen S, Hu S (2022) Microporous spongy scaffolds based on biodegradable elastic polyurethanes for the migration and growth of host cells. ACS Appl Polym Mater 4(5):3942–3951

    Article  CAS  Google Scholar 

  • Jung KW (2009) Perspectives on human stem cell research. J Cell Physiol 220(3):535–537. https://doi.org/10.1002/jcp.21786

    Article  CAS  PubMed  Google Scholar 

  • Khosrav MSM, Naser P, Seyyed MR, Agha GHH (1393) Investigating the effect of platelet rich plasma platelet on the propagation and differentiation of adipose-bone mesenchymal stem cells. Urmia Med J 25(5):453–462

    Google Scholar 

  • Kouser S, Prabhu A, Prashantha K, Nagaraja G, D’souza JN, Navada KM, Qurashi A, Manasa D (2022) Modified halloysite nanotubes with Chitosan incorporated PVA/PVP bionanocomposite films: thermal, mechanical properties and biocompatibility for tissue engineering. Colloids Surf A 634:127941

    Article  CAS  Google Scholar 

  • Kuang W, Mather PT (2018) A latent crosslinkable PCL-based polyurethane: Synthesis, shape memory, and enzymatic degradation. J Mater Res 33(17):2463–2476

    Article  ADS  CAS  Google Scholar 

  • Laschke MWST, Scheuer C, Kleer S, Shadmanov T, Eglin D, Alini M, Menger MD (2014) In vitro osteogenic differentiation of adipose-derived mesenchymal stem cell spheroids impairs their in vivo vascularization capacity inside implanted porous polyurethane scaffolds. Acta Biomater 10(10):4226–4235

    Article  CAS  PubMed  Google Scholar 

  • Laurenti M, Cauda V (2017) ZnO nanostructures for tissue engineering applications. Nanomaterials 7(11):374

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee WCLC, Shi H, Tang LA, Wang Y, Lim CT, Loh KP (2011) Origin of enhanced stem cell growth and differentiation on graphene and graphene oxide. ACS Nano 5(9):7334–73341

    Article  CAS  PubMed  Google Scholar 

  • Lu P-J, Fu W-E, Huang S-C, Lin C-Y, Ho M-L, Chen Y-P, Cheng H-F (2018) Methodology for sample preparation and size measurement of commercial ZnO nanoparticles. J Food Drug Anal 26(2):628–636

    Article  CAS  PubMed  Google Scholar 

  • MacDonald RS (2000) The role of zinc in growth and cell proliferation. J Nutr 130(5S Suppl):1500S-1508S. https://doi.org/10.1093/jn/130.5.1500S

    Article  CAS  PubMed  Google Scholar 

  • Mishra PKMH, Ekielski A, Talegaonkar S, Vaidya B (2017) Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications. Drug Discov Today 22(12):1825–1834. https://doi.org/10.1016/j.drudis.2017.08.006

    Article  CAS  PubMed  Google Scholar 

  • Mooney EDP, Greiser U, Murphy M, Barron V (2008) Carbon nanotubes and mesenchymal stem cells: biocompatibility, proliferation and differentiation 88: 2137–2143. https://doi.org/10.1021/nl073300o

  • Nie S (2009) Biomedical nanotechnology for molecular imaging, diagnostics, and targeted therapy. Engineering in Medicine and Biology Society, 2009. EMBC 2009. Annual International Conference of the IEEE, IEEE

  • Norouz F, Halabian R, Salimi A, Ghollasi M (2019) A new nanocomposite scaffold based on polyurethane and clay nanoplates for osteogenic differentiation of human mesenchymal stem cells in vitro. Mater Sci Eng C Mater Biol Appl 103:109857. https://doi.org/10.1016/j.msec.2019.109857

    Article  CAS  PubMed  Google Scholar 

  • Oh SH, Park IK, Kim JM, Lee JH (2007) In vitro and in vivo characteristics of PCL scaffolds with pore size gradient fabricated by a centrifugation method. Biomaterials 28(9):1664–1671. https://doi.org/10.1016/j.biomaterials.2006.11.024

    Article  CAS  PubMed  Google Scholar 

  • Osman DAM, Mustafa MA (2015) Synthesis and characterization of zinc oxide nanoparticles using zinc acetate dihydrate and sodium hydroxide. J Nanosci Nanoeng 1(4):248–251

    Google Scholar 

  • Parameswaran S, Verma RS (2011) Scanning electron microscopy preparation protocol for differentiated stem cells. Anal Biochem 416(2):186–190

    Article  CAS  PubMed  Google Scholar 

  • Pinho AR, Martins F, Costa MEV, Senos AM, da CruzeSilva OA, Pereira MDL, Rebelo S (2020) In vitro cytotoxicity effects of zinc oxide nanoparticles on spermatogonia cells. Cells 9(5):1081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramalingam M, Haidar Z, Ramakrishna S (2004) Nano-fibrous scaffolds for tissue engineering. J Colloids Surf B Biointerfaces

  • Ramezanifard R, Seyedjafari E, Ardeshirylajimi A, Soleimani M (2016) Biomimetic scaffolds containing nanofibers coated with willemite nanoparticles for improvement of stem cell osteogenesis. Mater Sci Eng C Mater Biol Appl 62:398–406. https://doi.org/10.1016/j.msec.2016.01.089

    Article  CAS  PubMed  Google Scholar 

  • Rink L (2000) Zinc and the immune system. 2000, 59, 541–552. Proc Nutr Soc 59(3):541–552

    Article  CAS  PubMed  Google Scholar 

  • Roach H (1994) Why does bone matrix contain non-collagenous proteins? The possible roles of osteocalcin, osteonectin, osteopontin and bone sialoprotein in bone mineralisation and resorption. Cell Biol Int 18(6):617–628

    Article  CAS  PubMed  Google Scholar 

  • Rohani Z, Ghollasi M, Aghamollaei H, Saidi H, Halabian R, Kheirollahzadeh F, Poormoghadam D (2022) A new hydrogel with fluorapatite nanoparticles for osteogenic differentiation of human adipose-derived stem cells in tissue engineering field. Cell Tissue Res 390(3):399–411

    Article  CAS  PubMed  Google Scholar 

  • Saeedi P, Halabian R, Fooladi AAI (2019) Antimicrobial effects of mesenchymal stem cells primed by modified LPS on bacterial clearance in sepsis. J Cell Physiol 234(4):4970–4986

    Article  CAS  PubMed  Google Scholar 

  • Salgado AJ, Coutinho OP, Reis RL (2004) Bone tissue engineering: state of the art and future trends. Macromol Biosci 4(8):743–765. https://doi.org/10.1002/mabi.200400026

    Article  CAS  PubMed  Google Scholar 

  • Shahrousvand M, Sadeghi GMM, Shahrousvand E, Ghollasi M, Salimi A (2017) Superficial physicochemical properties of polyurethane biomaterials as osteogenic regulators in human mesenchymal stem cells fates. Colloids Surf, B 156:292–304

    Article  CAS  Google Scholar 

  • Singh A, Kumari K, Kundu P (2022) Polyurethane Nanocomposites for Bone Tissue Engineering. Springer, Engineered Nanomaterials for Innovative Therapies and Biomedicine, pp 373–403

    Google Scholar 

  • Sun S, Guo Z, Xiao X, Liu B, Liu X, Tang PH, Mao N (2003) Isolation of mouse marrow mesenchymal progenitors by a novel and reliable method. Stem Cells 21(5):527–535. https://doi.org/10.1634/stemcells.21-5-527

    Article  CAS  PubMed  Google Scholar 

  • Termine JD, Kleinman HK, Whitson SW, Conn KM, McGarvey ML, Martin GR (1981) Osteonectin, a bone-specific protein linking mineral to collagen. Cell 26(1 Pt 1):99–105. https://doi.org/10.1016/0092-8674(81)90037-4

    Article  CAS  PubMed  Google Scholar 

  • Ullah S, Zainol I, Idrus RH (2017) Incorporation of zinc oxide nanoparticles into chitosan-collagen 3D porous scaffolds: Effect on morphology, mechanical properties and cytocompatibility of 3D porous scaffolds. Int J Biol Macromol 104:1020–1029

    Article  CAS  PubMed  Google Scholar 

  • Unger RE, Peters K, Huang Q, Funk A, Paul D, Kirkpatrick CJ (2005) Vascularization and gene regulation of human endothelial cells growing on porous polyethersulfone (PES) hollow fiber membranes. Biomaterials 26(17):3461–3469. https://doi.org/10.1016/j.biomaterials.2004.09.047

    Article  CAS  PubMed  Google Scholar 

  • Vater C, Kasten P, Stiehler M (2011) Culture media for the differentiation of mesenchymal stromal cells. Acta Biomater 7(2):463–477. https://doi.org/10.1016/j.actbio.2010.07.037

    Article  CAS  PubMed  Google Scholar 

  • Vigneshwaran N, Kumar S, Kathe A, Varadarajan P, Prasad V (2006) Functional finishing of cotton fabrics using zinc oxide–soluble starch nanocomposites. Nanotechnology 17(20):5087

    Article  ADS  CAS  Google Scholar 

  • Wang J, Liu B, Teng Z, Zhou X, Wang X, Zhang B, Lu G, Niu X, Yang Y, Deng X (2017) Phloretin attenuates listeria monocytogenes virulence both in vitro and in vivo by simultaneously targeting listeriolysin o and sortase A. Front Cell Infect Microbiol 7:9. https://doi.org/10.3389/fcimb.2017.00009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang QCB, Cao M, Sun J, Wu H, Zhao P, Xing J, Yang Y, Zhang X, Ji M, Gu N (2016) Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs. Biomaterials 2016(86):11–20

    Google Scholar 

  • Xue RQY, Li L, Yao G, Yang L, Sun Y (2017) Polycaprolactone nanofiber scaffold enhances the osteogenic differentiation potency of various human tissue-derived mesenchymal stem cells. Stem Cell Res Ther 8(1):148–156

    Article  PubMed  PubMed Central  Google Scholar 

  • Yaghoobi MH-NS, Soleimani M, Vasheghani-Farahani E, Mousavi SM (2016) Osteogenic differentiation and mineralization on compact multilayer nHA-PCL electrospun scaffolds in a perfusion bioreactor. Iran J Biotechnol 14(2):41–49

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang XLY, Liu X, Huang Q, Zhang R, Feng Q (2018) Incorporation of silica nanoparticles to PLGA electrospun fibers for osteogenic differentiation of human osteoblast-like cells. Regen Biomater 5(4):229–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye JH, Xu YJ, Gao J, Yan SG, Zhao J, Tu Q, Zhang J, Duan XJ, Sommer CA, Mostoslavsky G, Kaplan DL, Wu YN, Zhang CP, Wang L, Chen J (2011) Critical-size calvarial bone defects healing in a mouse model with silk scaffolds and SATB2-modified iPSCs. Biomaterials 32(22):5065–5076. https://doi.org/10.1016/j.biomaterials.2011.03.053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yi CLD, Fong CC, Zhang J, Yang M (2010) Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. ACS Nano 4(11):6439–6448

    Article  CAS  PubMed  Google Scholar 

  • Yin T, Li L (2006) The stem cell niches in bone. J Clin Invest 116(5):1195–1201. https://doi.org/10.1172/JCI28568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Webster TJ (2009) Nanotechnology and nanomaterials: promises for improved tissue regeneration. Nano Today 4(1):66–80

    Article  CAS  Google Scholar 

  • Zheng K, Lu M, Rutkowski B, Dai X, Yang Y, Taccardi N, Stachewicz U, Czyrska-Filemonowicz A, Huser N, Boccaccini AR (2016) ZnO quantum dots modified bioactive glass nanoparticles with pH-sensitive release of Zn ions, fluorescence, antibacterial and osteogenic properties. J Mater Chem B 4(48):7936–7949. https://doi.org/10.1039/c6tb02053d

    Article  CAS  PubMed  Google Scholar 

  • Zhou XZ, Leung VY, Dong QR, Cheung KM, Chan D, Lu WW (2008) Mesenchymal stem cell-based repair of articular cartilage with polyglycolic acid-hydroxyapatite biphasic scaffold. Int J Artif Organs 31(6):480–489. https://doi.org/10.1177/039139880803100603

    Article  CAS  PubMed  Google Scholar 

  • Zhu DSY, Young ML, Ma J, Zheng Y, Tang L (2017) Biological responses and mechanisms of human bone marrow mesenchymal stem cells to Zn and Mg biomaterials. ACS Appl Mater Interfaces 9:27453–27461

    Article  CAS  PubMed  Google Scholar 

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Norozi, S., Ghollasi, M., Salimi, A. et al. Mesenchymal stem cells osteogenic differentiation by ZnO nanoparticles and polyurethane bimodal foam nanocomposites. Cell Tissue Bank 25, 167–185 (2024). https://doi.org/10.1007/s10561-023-10090-4

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