AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.8351
Submit to IJB
Cite this article
24
Download
577
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
RESEARCH ARTICLE

Osteogenesis induced by magnetic responsive composite scaffolds under a static magnetic field

ShuangShuang Zhuo1 ,  Ming Zhang2 ,  YongQiang Zhang3 ,  Xin Zhang4 ,  Rui Sang5 ,  Xin Fang4 ,  YiRan Yao1 ,  TingYue Qi1*
Show Less
1 Department of Ultrasound, Medical Imaging Center, Affiliated Hospital of Yangzhou University, Yangzhou, China
2 Department of Orthopaedic Surgery, The Second Hospital of Nanjing, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine , Nanjing, Jiangsu, China
3 Department of Orthopedics, Northern Jiangsu People’s Hospital, Yangzhou, China
4 Department of Orthopaedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
5 Health Management Center, Affiliated Hospital of Yangzhou University, Yangzhou, China
IJB, 8351 https://doi.org/10.36922/ijb.8351
Received: 31 December 2024 | Accepted: 25 February 2025 | Published online: 25 February 2025
(This article belongs to the Special Issue 3D Printing Biomedical Polymer Materials)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Currently, traditional osteogenesis methods face significant challenges in terms of therapeutic efficiency and biocompatibility, particularly in the context of bone repair where higher precision and efficacy are required. In this study, we fabricated a novel composite scaffold composed of polycaprolactone (PCL), polydopamine (PDA), and iron oxide nanoparticles (IONPs) and investigated its osteogenic potential. The incorporation of IONPs imparts magnetic responsiveness to the scaffold, thereby enabling the application of an external magnetic field to stimulate osteogenesis. Characterization of the scaffold confirmed its structural integrity, porosity, and biocompatibility, whereas the inclusion of PDA improved its hydrophilicity and cell adhesion properties. In vitro studies demonstrated that an external magnetic field significantly enhanced cell proliferation, osteogenic differentiation, and mineral deposition of osteoprogenitor cells cultured on the scaffolds. Furthermore, in vivo evaluation revealed that when the scaffold was exposed to magnetic stimulation, bone regeneration was accelerated, and integration of the defect site was improved. The magnetic-field-mediated approach proposed in this study effectively enhanced the osteogenic rate by augmenting the magnetic responsiveness of IONPs and combining the biocompatibility and cell-adhesion-promoting functions of PCL/PDA. This method offers a more controllable and biologically responsive alternative strategy for bone tissue regeneration with considerable potential for clinical applications.

Graphical abstract
Keywords
Bone regeneration
Bone remodeling
Iron oxide nanoparticles
Static magnetic fields
Funding
This work was financially supported by the Guiding Project of Social Development of Yangzhou City (Grant/Award Number: YZ2024118), the Natural Science Foundation of Jiangsu Province (Grant Number: BK20230704), and the Special Fund for Medical Innovation and Transformation of Yangzhou University (Grant/Award Number: AHYZUCXTD202106).
Conflict of interest
The authors declare they have no competing interests.
References
  1. Park J, Lee SJ, Jung TG, et al. Surface modification of a three-dimensional polycaprolactone scaffold by polydopamine, biomineralization, and BMP-2 immobilization for potential bone tissue applications. Colloids Surf B Biointerfaces. 2021;199:111528. doi: 10.1016/j.colsurfb.2020.111528
  2. Li J, Yao Q, Xu Y, et al. Lithium chloride-releasing 3D printed scaffold for enhanced cartilage regeneration. Med Sci Monit. 2019;25:4041-4050. doi: 10.12659/MSM.916918
  3. Dong Q, Zhang M, Zhou X, et al. 3D-printed Mg-incorporated PCL-based scaffolds: a promising approach for bone healing. Mater Sci Eng C Mater Biol Appl. 2021;129:112372. doi: 10.1016/j.msec.2021.112372
  4. Elahi N, Rizwan M. Progress and prospects of magnetic iron oxide nanoparticles in biomedical applications: a review. Artif Organs. 2021;45(11):1272-1299. doi: 10.1111/aor.14027
  5. Alcala-Orozco CR, Mutreja I, Cui X, et al. Hybrid biofabrication of 3D osteoconductive constructs comprising Mg-based nanocomposites and cell-laden bioinks for bone repair. Bone. 2022;154:116198. doi: 10.1016/j.bone.2021.116198
  6. Li J, Li L, Zhou J, et al. 3D printed dual-functional biomaterial with self-assembly micro-nano surface and enriched nano argentum for antibacterial and bone regeneration. Appl Mater Today. 2019;17:206-215. doi: 10.1016/j.apmt.2019.06.012
  7. Kong N, Yang H, Tian R, et al. An injectable self-adaptive polymer as a drug carrier for the treatment of nontraumatic early stage osteonecrosis of the femoral head. Bone Res. 2022;10(1):28. doi: 10.1038/s41413-022-00196-y
  8. Cheng YL, Chen YW, Wang K, et al. Enhanced adhesion and differentiation of human mesenchymal stem cells inside apatite-mineralized/poly(dopamine)-coated poly(epsilon-caprolactone) scaffolds by stereolithography. J Mater Chem B. 2016;4(38): 6307-6315. doi: 10.1039/c6tb01377e
  9. Lutter G, Puehler T, Cyganek L, et al. Biodegradable poly- ε-caprolactone scaffolds with ECFCs and iMSCs for tissue-engineered heart valves. Int J Mol Sci. 2022;23(1):527. doi: 10.3390/ijms23010527
  10. Abdelaziz D, Hefnawy A, Al-Wakeel E, et al. New biode­gradable nanoparticles-in-nanofiber-based membranes for guided periodontal tissue and bone regeneration with enhanced antibacterial activity. J Adv Res. 2021;28:51-62. doi: 10.1016/j.jare.2020.06.014
  11. Dikici S, Aldemir Dikici B, MacNeil S, et al. Decellularized extracellular matrix decorated PCL PolyHIPE scaffolds for enhanced cellular activity, integration, and angiogenesis. Biomater Sci. 2021;9(21):7297-7310. doi: 10.1039/d1bm01262b
  12. Wei P, Xu Y, Zhang H, et al. Continued sustained insulin-releasing PLGA nanoparticles modified 3D-Printed PCL composite scaffolds for osteochondral repair. Chem Eng J. 2021;422:130051. doi: 10.1016/j.cej.2021.130051
  13. Kao CY, Lin TL, Lin YH, et al. Synergistic effect of static magnetic fields and 3D-printed iron-oxide-nanoparticle-containing calcium silicate/poly-ε-caprolactone scaffolds for bone tissue engineering. Cells. 2022;11(24):3967. doi: 10.3390/cells11243967
  14. Li L, Li J, Guo J, et al. 3D molecularly functionalized cell-free biomimetic scaffolds for osteochondral regeneration. Adv Funct Mater. 2019;29(6):1807356. doi: 10.1002/adfm.201807356
  15. Liu Y, Peng L, Li L, et al. 3D-bioprinted BMSC-laden biomimetic multiphasic scaffolds for efficient repair of osteochondral defects in an osteoarthritic rat model. Biomaterials. 2021;279:121216. doi: 10.1016/j.biomaterials.2021.121216
  16. Ge R, Li X, Lin M, et al. Fe3O4@polydopamine composite theranostic superparticles employing packed Fe3O4 nanoparticles as the core. ACS Appl Mater Interfaces. 2016;8(35):22942-22952. doi: 10.1021/acsami.6b07997
  17. Karahaliloğlu Z, Yalçın E, Demirbilek M, et al., 2017, Magnetic silk fibroin e-gel scaffolds for bone tissue engineering applications. J Bioact Compat Polym. 2017;32(6):596-614. doi: 10.1177/0883911517693635
  18. Fini M, Cadossi R, Canè V, et al. The effect of pulsed electromagnetic fields on the osteointegration of hydroxyapatite implants in cancellous bone: a morphologic and microstructural in vivo study. J Orthop Res. 2002;20(4):756-763. doi: 10.1016/s0736-0266(01)00158-9
  19. Wu XD, Kang L, Tian J, et al. Exosomes derived from magnetically actuated bone mesenchymal stem cells promote tendon-bone healing through the miR-21-5p/ SMAD7 pathway. Mater Today Bio. 2022;15:100319. doi: 10.1016/j.mtbio.2022.100319
  20. Sun J, Liu X, Huang J, et al. Magnetic assembly mediated enhancement of differentiation of mouse bone marrow cells cultured on magnetic colloidal assemblies. Sci Rep. 2014;4:5125. doi: 10.1038/srep05125
  21. Huang Z, He Y, Chang X, et al. A magnetic iron oxide/ polydopamine coating can improve osteogenesis of 3D-printed porous titanium scaffolds with a static magnetic field by upregulating the TGFβ-Smads pathway. Adv Healthc Mater. 2020;9(14):e2000318. doi: 10.1002/adhm.202000318
  22. Yan Z, Sun T, Tan W, et al. Magnetic field boosts the transmembrane transport efficiency of magnesium ions from PLLA bone scaffold. Small. 2023;19(40): e2301426. doi: 10.1002/smll.202301426
  23. Wang Q, Chen B, Ma F, et al. Magnetic iron oxide nanoparticles accelerate osteogenic differentiation of mesenchymal stem cells via modulation of long noncoding RNA INZEB2. Nano Res. 2016;10(2):626-642. doi: 10.1007/s12274-016-1322-4
  24. Abar E, Vandghanooni S, Torab A, et al. A comprehensive review on nanocomposite biomaterials based on gelatin for bone tissue engineering. Int J Biol Macromol. 2024; 254(Pt 1):127556. doi: 10.1016/j.ijbiomac.2023.127556
  25. García-Lamas L, Lozano D, Jiménez-Díaz, V, et al. Enriched mesoporous bioactive glass scaffolds as bone substitutes in critical diaphyseal bone defects in rabbits. Acta Biomater. 2024;180:104-114. doi: 10.1016/j.actbio.2024.04.005
  26. Zheng L, Zhuang Z, Li Y, et al. Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis. Bioact Mater. 2022;14:250-261. doi: 10.1016/j.bioactmat.2021.11.012
  27. Kim EC, Leesungbok R, Lee SW, et al. Effects of moderate-intensity static magnetic fields on human bone marrow-derived mesenchymal stem cells. Bioelectromagnetics. 2015;36(4):267-276. doi: 10.1002/bem.21903
  28. Liao W, Lu J, Wang Q, et al. Osteogenesis of iron oxide nanoparticle-labeled human precartilaginous stem cells in penetrating network table hydrogel. Front Bioeng Biotechnol. 2022;10:872149. doi: 10.3389/fbioe.2022.872149
  29. Fu C, Jiang Y, Yang X, et al. Mussel-inspired gold nanoparticles and PLGA/L-Lysine-g-graphene oxide composite scaffolds for bone defect repair. Int J Nanomedicine. 2021;16:6693-6718. doi: 10.2147/ijn.S328390
  30. Ghorbani F, Kim M, Monavari M, et al. Mussel-inspired polydopamine-decorated alginate dialdehyde-gelatin 3D printed scaffolds for bone tissue engineering applications. Front Bioeng Biotechnol. 2022;10:940070. doi: 10.3389/fbioe.2022.940070
  31. Li Y, Wu R, Yu L, et al. Rational design of nonstoichiometric bioceramic scaffolds via digital light processing: tuning chemical composition and pore geometry evaluation. J Biol Eng. 2021;15(1):1. doi: 10.1186/s13036-020-00252-3
  32. Gharibshahian M, Salehi M, Beheshtizadeh N, et al. Recent advances on 3D-printed PCL-based composite scaffolds for bone tissue engineering. Front Bioeng Biotechnol. 2023;11:1168504. doi: 10.3389/fbioe.2023.1168504
  33. Zhang X, Yan Q, Liu X, et al. LncRNA00638 promotes the osteogenic differentiation of periodontal mesenchymal stem cells from periodontitis patients under static mechanical strain. Stem Cell Res Ther. 2023;14(1):177. doi: 10.1186/s13287-023-03404-6
  34. Bedford EE, Méthivier CM, Pradier C, et al. Nanostructured and spiky gold shell growth on magnetic particles for SERS applications. Nanomaterials (Basel). 2020;10(11):2136. doi: 10.3390/nano10112136
  35. Song X, Liu X, Ma Y, et al. Synthesis of Ce/Gd@HA/PLGA scaffolds contributing to bone repair and MRI enhancement. Front Bioeng Biotechnol. 2022;10:834226. doi: 10.3389/fbioe.2022.834226
  36. Li X, Wei Z, Lv H, et al. Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites. Int J Nanomedicine. 2019;14:573-589. doi: 10.2147/IJN.S184920
  37. Wang S, Gu R, Wang F, et al. 3D-printed PCL/Zn scaffolds for bone regeneration with a dose-dependent effect on osteogenesis and osteoclastogenesis. Mater Today Bio. 2022;13:100202. doi: 10.1016/j.mtbio.2021.100202
  38. Li D, Zheng S, Wei P, et al. Synchronized long-term delivery of growth hormone and insulin-like growth factor 1 through poly (lactic-co-glycolic acid) nanoparticles on polycaprolactone scaffolds for enhanced osteochondral regeneration. Int J Biol Macromol. 2024;282(Pt 4):136781. doi: 10.1016/j.ijbiomac.2024.136781
  39. Xu J, Liu K, Chen T, et al. Rotating magnetic field delays human umbilical vein endothelial cell aging and prolongs the lifespan of Caenorhabditis elegans. Aging (Albany NY). 2019;11(22):10385-10408. doi: 10.18632/aging.102466
  40. Chen G, Zhuo Y, Tao B, et al. Moderate SMFs attenuate bone loss in mice by promoting directional osteogenic differentiation of BMSCs. Stem Cell Res Ther. 2020;11(1):487. doi: 10.1186/s13287-020-02004-y
  41. Marycz K, Alicka M, Kornicka-Garbowska K, et al. 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. J Biomed Mater Res B Appl Biomater. 2020;108(4):1398-1411. doi: 10.1002/jbm.b.34488
  42. Meng J, Xiao B, Zhang Y, et al. Super-paramagnetic responsive nanofibrous scaffolds under static magnetic field enhance osteogenesis for bone repair in vivo. Sci Rep. 2013;3:2655. doi: 10.1038/srep02655
  43. Mouthuy PA, Somogyi Škoc M, Čipak Gašparović A, et al. Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications. Int J Nanomedicine. 2017;12:3977-3991. doi: 10.2147/ijn.S133326
  44. Zhao YZ, Chen R, Xue PP, et al. Magnetic PLGA microspheres loaded with SPIONs promoted the reconstruction of bone defects through regulating the bone mesenchymal stem cells under an external magnetic field. Mater Sci Eng C Mater Biol Appl. 2021;122:111877. doi: 10.1016/j.msec.2021.111877
  45. Fujita T, Azuma Y, Fukuyama R, et al. Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling. J Cell Biol. 2004;166(1):85-95. doi: 10.1083/jcb.200401138
  46. Madel MB, Ibáñez L, Ciucci T, et al. Dissecting the phenotypic and functional heterogeneity of mouse inflammatory osteoclasts by the expression of Cx3cr1. Elife. 2020;9:e54493. doi: 10.7554/eLife.54493
  47. Ruolan W, Liangjiao C, Longquan S. The mTOR/ULK1 signaling pathway mediates the autophagy-promoting and osteogenic effects of dicalcium silicate nanoparticles. J Nanobiotechnology. 2020;18(1):119. doi: 10.1186/s12951-020-00663-w
  48. Kaliannagounder VK, Hossain MA, Kim JH, et al. Magnetic hydroxyapatite composite nanoparticles for augmented differentiation of MC3T3-E1 cells for bone tissue engineering. Mar Drugs. 2023;21(2):85. doi: 10.3390/md21020085
  49. Liu TM, Lee EH. Transcriptional regulatory cascades in Runx2-dependent bone development. Tissue Eng Part B Rev. 2013;19(3):254-263. doi: 10.1089/ten.TEB.2012.0527
  50. Li W, Huang C, Ma T, et al. Low-frequency electromagnetic fields combined with tissue engineering techniques accelerate intervertebral fusion. Stem Cell Res Ther. 2021;12(1):143 doi: 10.1186/s13287-021-02207-x
  51. Wang Q, Chen B, Cao M, et al. Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs. Biomaterials. 2016;86:11-20. doi: 10.1016/j.biomaterials.2016.02.004
  52. Gokduman K, Bestepe F, Li L, et al. Dose-, treatment- and time-dependent toxicity of superparamagnetic iron oxide nanoparticles on primary rat hepatocytes. Nanomedicine (Lond). 2018;13(11):1267-1284. doi: 10.2217/nnm-2017-0387
  53. Jain TK, Reddy MK, Morales MA, et al. Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats. Mol Pharm. 2008;5(2): 316-327. doi: 10.1021/mp7001285
  54. Levy M, Luciani N, Alloyeau D, et al. Long term in vivo biotransformation of iron oxide nanoparticles. Biomaterials. 2011;32(16):3988-3999. doi: 10.1016/j.biomaterials.2011.02.031
  55. Marsell R, Einhorn TA. The biology of fracture healing. Injury. 2011;42(6):551-555. doi: 10.1016/j.injury.2011.03.031
  56. Yang J, Gao H, Zhang D, et al. Static compressive behavior and material failure mechanism of trabecular tantalum scaffolds fabricated by laser powder bed fusion-based additive manufacturing. Int J Bioprint. 2022;8(1):438. doi: 10.18063/ijb.v8i1.438
  57. Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005;26(27): 5474-5491. doi: 10.1016/j.biomaterials.2005.02.002
  58. Jiang P, Zhang Y, Zhu C, et al. Fe(3)O(4)/BSA particles induce osteogenic differentiation of mesenchymal stem cells under static magnetic field. Acta Biomater. 2016; 46:141-150. doi: 10.1016/j.actbio.2016.09.020
  59. Chen H, Sun J, Wang Z, et al. Magnetic cell-scaffold interface constructed by superparamagnetic IONP enhanced osteogenesis of adipose-derived stem cells. ACS Appl Mater Interfaces. 2018;10(51):44279-44289 doi: 10.1021/acsami.8b17427
  60. Yang J, Wu J, Guo Z, et al. Iron oxide nanoparticles combined with static magnetic fields in bone remodeling. Cells. 2022;11(20):3298. doi: 10.3390/cells11203298.

 

 

 

 

 

 

Share
Back to top
International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept