Promotion through external magnetic field of osteogenic differentiation potential in adipose‐derived mesenchymal stem cells: Design of polyurethane/poly(lactic) acid sponges doped with iron oxide nanoparticles

Marycz, Krzysztof; Alicka, Michalina; Kornicka, Katarzyna; Polnar, Joanna; Lis-Bartos, Anna; Wiglusz, Rafał J.; Roecken, Michael; Nédélec, Jean-Marie

doi:10.1002/jbm.b.34488

Cited by 18 publications

(14 citation statements)

References 30 publications

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“…As a negative control, cell lines culturing without exposure to the magnetic field were used (MF-). The system for magnetic field generation was described in detail by Marycz et al 34 . The magnetic field stimulation system was installed in CO 2 incubator and established to 0.2 T.…”

Section: Methodsmentioning

confidence: 99%

Nanohydroxyapatite (nHAp) Doped with Iron Oxide Nanoparticles (IO), miR-21 and miR-124 Under Magnetic Field Conditions Modulates Osteoblast Viability, Reduces Inflammation and Inhibits the Growth of Osteoclast – A Novel Concept for Osteoporosis Treatment: Part 1

Marycz

Śmieszek

Marcinkowska

et al. 2021

IJN

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Purpose: Osteoporosis results in a severe decrease in the life quality of many people worldwide. The latest data shows that the number of osteoporotic fractures is becoming an increasing international health service problem. Therefore, a new kind of controllable treatment methods for osteoporotic fractures is extensively desired. For that reason, we have manufactured and evaluated nanohydroxyapatite (nHAp)-based composite co-doped with iron oxide (IO) nanoparticles. The biomaterial was used as a matrix for the controlled delivery of miR-21-5p and miR-124-3p, which have a proven impact on bone cell metabolism. Methods: The nanocomposite Ca 5 (PO 4 ) 3 OH/Fe 3 O 4 (later called nHAp/IO) was obtained by the wet chemistry method and functionalised with microRNAs (nHAp/IO@miR-21/124). Its physicochemical characterization was performed using XRPD, FT-IR, SEM-EDS and HRTEM and SAED methods. The modulatory effect of the composite was tested in vitro using murine pre-osteoblasts MC3T3-E1 and pre-osteoclasts 4B12. Moreover, the anti-inflammatory effects of biomaterial were analysed using a model of LPS-treated murine macrophages RAW 264.7. We have analysed the cells' viability, mitochondria membrane potential and oxidative stress under magnetic field (MF+) and without (MF-). Moreover, the results were supplemented with RT-qPCR and Western blot assays to evaluate the expression profile for master regulators of bone metabolism. Results: The results indicated pro-osteogenic effects of nHAp/IO@miR-21/124 composite enhanced by exposure to MF. The enhanced osteogenesis guided by nHAp/IO@miR-21/124 presence was associated with increased metabolism of progenitor cells and activation of osteogenic markers (Runx-2, Opn, Coll-1). Simultaneously, nanocomposite decreased metabolism and differentiation of pre-osteoclastic 4B12 cells accompanied by reduced expression of CaII and Ctsk. Obtained composite regulated viability of bone progenitor cells and showed immunomodulatory properties inhibiting the expression of inflammatory markers, ie, TNF-α, iNOs or IL-1β, in LPS-stimulated RAW 264.7 cells. Conclusion:We have described for the first time a new concept of osteoporosis treatment based on nHAp/IO@miR-21/124 application. Obtained results indicated that fabricated nanocomposite might impact proper regeneration of osteoporotic bone, restoring the balance between osteoblasts and osteoclast.

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Section: Methodsmentioning

confidence: 99%

Nanohydroxyapatite (nHAp) Doped with Iron Oxide Nanoparticles (IO), miR-21 and miR-124 Under Magnetic Field Conditions Modulates Osteoblast Viability, Reduces Inflammation and Inhibits the Growth of Osteoclast – A Novel Concept for Osteoporosis Treatment: Part 1

Marycz

Śmieszek

Marcinkowska

et al. 2021

IJN

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“…The stimulation of osteoblasts for differentiation and inhibition of osteoclasts activity seems to be a key component in the course of osteoporotic bone regeneration. Recently, we have shown that magnetic iron nanoparticles (IOs) enhance progenitor cells osteogenic activity which supports their application in regenerative medicine [19].…”

Section: Discussionmentioning

confidence: 90%

“…Cells were exposed to magnetic field using system was designed at the Institute of Low Temperature and Structure Research Polish Academy of Science in Wroclaw as described previously [19]. The MF strength equalled 0.2 T. The cell culture plate of following size 127.89 × 85.6 × 19.69 mm was placed between magnets, and all systems were installed in CO 2 incubator.…”

Section: Experimental Settingmentioning

confidence: 99%

“…This results in significant reduction of necessary surgical intervention, application of maximum dose of drugs, and avoidance of toxic side effects on other organs. Our own previous studies revealed that magnetic promote osteogenic differentiation potential of stem progenitor cells under magnetic field condition through activation of particular integrin's [19].…”

Section: Introductionmentioning

confidence: 97%

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Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action

Marycz¹,

Sobierajska²,

Roecken³

et al. 2020

J Nanobiotechnol

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Background: Prevalence of osteoporosis is rapidly growing and so searching for novel therapeutics. Yet, there is no drug on the market available to modulate osteoclasts and osteoblasts activity simultaneously. Thus in presented research we decided to fabricate nanocomposite able to: (i) enhance osteogenic differentiation of osteoblast, (i) reduce osteoclasts activity and (iii) reduce pro-inflammatory microenvironment. As a consequence we expect that fabricated material will be able to inhibit bone loss during osteoporosis. Results:The α-Fe 2 O 3 /γ-Fe 2 O 3 nanocomposite (IOs) was prepared using the modified sol-gel method. The structural properties, size, morphology and Zeta-potential of the particles were studied by means of XRPD (X-ray powder diffraction), SEM (Scanning Electron Microscopy), PALS and DLS techniques. The identification of both phases was checked by the use of Raman spectroscopy and Mössbauer measurement. Moreover, the magnetic properties of the obtained IOs nanoparticles were determined. Then biological properties of material were investigated with osteoblast (MC3T3), osteoclasts (4B12) and macrophages (RAW 264.7) in the presence or absence of magnetic field, using confocal microscope, RT-qPCR, western blot and cell analyser. Here we have found that fabricated IOs: (i) do not elicit immune response; (ii) reduce inflammation; (iii) enhance osteogenic differentiation of osteoblasts; (iv) modulates integrin expression and (v) triggers apoptosis of osteoclasts. Conclusion:Fabricated by our group α-Fe 2 O 3 /γ-Fe 2 O 3 nanocomposite may become an justified and effective therapeutic intervention during osteoporosis treatment.

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“…Cells were exposed to a magnetic field using the system designed at the Institute of Low Temperature and Structure Research Polish Academy of Science in Wroclaw as described previously. 19…”

Section: Experimental Settingmentioning

confidence: 99%

Fe3O4 Magnetic Nanoparticles Under Static Magnetic Field Improve Osteogenesis via RUNX-2 and Inhibit Osteoclastogenesis by the Induction of Apoptosis

Marycz¹,

Sobierajska²,

Wiglusz³

et al. 2020

IJN

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The presented study aimed to investigate the effects of Fe 3 O 4 nanoparticles and static magnetic field on osteoblast and osteoclasts' metabolic activity. Methods: Magnetic nanoparticles were prepared by a wet chemical co-precipitation process and analyzed using X-ray powder diffraction, high-resolution transmission electron microscope (HRTEM), dynamic light scattering (DLS), laser Doppler velocimetry, Raman and the Mössbauer spectroscopy. In vitro experiments were performed using MC3T3, 4B12 and RAW 264.7 cell lines. Cells were cultured in the presence of nanoparticles and with or without exposure to the magnetic field. Proteins were investigated with Western blotting and immunofluorescence and Western blot. Gene expression was analyzed with a quantitative real-time polymerase chain reaction. Results: Obtained particles were in the nano-range (average size around 50 nm) and had a spherical-like morphology. The typical hydrodynamic size was in the range 178-202 nm and Zeta potential equaled -9.51 mV. Mössbauer spectrum corresponds to the Fe +3 ions in tetrahedral (A) and Fe +3 and Fe +2 ions in octahedral (B) sites of Fe 3 O 4 . In vitro study revealed cytocompatibility and anti-inflammatory effects of fabricated nanoparticles. Furthermore, it was shown that nanoparticles combined with magnetic field exposure enhance osteogenic differentiation of MC3T3 cells by upregulation of RUNX-2 activity. Under the same experimental condition, nanoparticles and magnetic field decreased osteoclastogenesis of 4B12 by the induction of apoptosis through the mitochondrial-dependent pathway. Conclusion: Fe 3 O 4 nanoparticles together with magnetic field can be applied for the fabrication of novel biomaterials for the treatment of bone disorders related to bone loss in which a balance between bone-forming and resorbing cells is disturbed.

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Promotion through external magnetic field of osteogenic differentiation potential in adipose‐derived mesenchymal stem cells: Design of polyurethane/poly(lactic) acid sponges doped with iron oxide nanoparticles

Cited by 18 publications

References 30 publications

Nanohydroxyapatite (nHAp) Doped with Iron Oxide Nanoparticles (IO), miR-21 and miR-124 Under Magnetic Field Conditions Modulates Osteoblast Viability, Reduces Inflammation and Inhibits the Growth of Osteoclast – A Novel Concept for Osteoporosis Treatment: Part 1

Nanohydroxyapatite (nHAp) Doped with Iron Oxide Nanoparticles (IO), miR-21 and miR-124 Under Magnetic Field Conditions Modulates Osteoblast Viability, Reduces Inflammation and Inhibits the Growth of Osteoclast – A Novel Concept for Osteoporosis Treatment: Part 1

Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action

<p>Fe<sub>3</sub>O<sub>4</sub> Magnetic Nanoparticles Under Static Magnetic Field Improve Osteogenesis via RUNX-2 and Inhibit Osteoclastogenesis by the Induction of Apoptosis</p>

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