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3D Printed Magneto‐Active Microfiber Scaffolds for Remote Stimulation and Guided Organization of 3D In Vitro Skeletal Muscle Models

Small, vol. 20, pp. e2307178

Abstract

This work reports the rational design and fabrication of magneto-active microfiber meshes with controlled hexagonal microstructures via melt electrowriting (MEW) of a magnetized polycaprolactone-based composite. In situ iron oxide nanoparticle deposition on oxidized graphene yields homogeneously dispersed magnetic particles with sizes above 0.5 µm and low aspect ratio, preventing cellular internalization and toxicity. With these fillers, homogeneous magnetic composites with high magnetic content (up to 20 weight %) are obtained and processed in a solvent-free manner for the first time. MEW of magnetic composites enabled the creation of skeletal muscle-inspired design of hexagonal scaffolds with tunable fiber diameter, reconfigurable modularity, and zonal distribution of magneto-active and nonactive material, with elastic tensile deformability. External magnetic fields below 300 mT are sufficient to trigger out-of-plane reversible deformation. In vitro culture of C2C12 myoblasts on three-dimensional (3D) Matrigel/collagen/MEW scaffolds showed that microfibers guided the formation of 3D myotube architectures, and the presence of magnetic particles does not significantly affect viability or differentiation rates after 8 days. Centimeter-sized skeletal muscle constructs allowed for reversible, continued, and dynamic magneto-mechanical stimulation. Overall, these innovative microfiber scaffolds provide magnetically deformable platforms suitable for dynamic culture of skeletal muscle, offering potential for in vitro disease modeling.

Authors 13

  1. Utrecht University · University Medical Center Utrecht · Eindhoven University of Technology

    Affiliation as printed

    Department of Biomedical Engineering Eindhoven University of Technology Eindhoven 5612 AE The Netherlands

    Department of Orthopaedics Regenerative Medicine Center Utrecht University Medical Center Utrecht Utrecht 3508 GA The Netherlands

    Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, 5612 AE The Netherlands

    Department of Orthopaedics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, 3508 GA The Netherlands

  2. Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

    Affiliation as printed

    Department of Anatomy and Embryology Leiden University Medical Center Leiden 2333 ZC The Netherlands

    Leiden Node The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) Leiden 2333 ZA The Netherlands

    Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, 2333 ZC The Netherlands

    Leiden Node, The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden, 2333 ZA The Netherlands

  3. Universidade do Porto

    Affiliation as printed

    ALiCE – Associate Laboratory in Chemical Engineering Faculty of Engineering University of Porto Porto 4200‐465 Portugal

    Departamento de Engenharia Química Faculty of Engineering University of Porto Porto 4200‐465 Portugal

  4. Utrecht University · University Medical Center Utrecht

    Affiliation as printed

    Department of Orthopaedics Regenerative Medicine Center Utrecht University Medical Center Utrecht Utrecht 3508 GA The Netherlands

    Department of Orthopaedics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, 3508 GA The Netherlands

  5. Utrecht University · University Medical Center Utrecht

    Affiliation as printed

    Department of Orthopaedics Regenerative Medicine Center Utrecht University Medical Center Utrecht Utrecht 3508 GA The Netherlands

    Department of Orthopaedics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, 3508 GA The Netherlands

  6. Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

    Affiliation as printed

    Department of Anatomy and Embryology Leiden University Medical Center Leiden 2333 ZC The Netherlands

    Leiden Node The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) Leiden 2333 ZA The Netherlands

    Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, 2333 ZC The Netherlands

    Leiden Node, The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden, 2333 ZA The Netherlands

  7. Universidade do Porto

    Affiliation as printed

    Departamento de Engenharia Química Faculty of Engineering University of Porto Porto 4200‐465 Portugal

  8. Universidade do Porto

    Affiliation as printed

    Departamento de Engenharia Química Faculty of Engineering University of Porto Porto 4200‐465 Portugal

  9. Universidade do Porto

    Affiliation as printed

    ALiCE – Associate Laboratory in Chemical Engineering Faculty of Engineering University of Porto Porto 4200‐465 Portugal

    Departamento de Engenharia Química Faculty of Engineering University of Porto Porto 4200‐465 Portugal

  10. Utrecht University · University Medical Center Utrecht

    Affiliation as printed

    Department of Clinical Sciences Faculty of Veterinary Medicine Utrecht University Utrecht 3508 GA The Netherlands

    Department of Orthopaedics Regenerative Medicine Center Utrecht University Medical Center Utrecht Utrecht 3508 GA The Netherlands

    Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3508 GA The Netherlands

    Department of Orthopaedics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, 3508 GA The Netherlands

  11. Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

    Affiliation as printed

    Department of Anatomy and Embryology Leiden University Medical Center Leiden 2333 ZC The Netherlands

    Leiden Node The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) Leiden 2333 ZA The Netherlands

    Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, 2333 ZC The Netherlands

    Leiden Node, The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden, 2333 ZA The Netherlands

  12. Universidade do Porto

    Affiliation as printed

    ALiCE – Associate Laboratory in Chemical Engineering Faculty of Engineering University of Porto Porto 4200‐465 Portugal

    Departamento de Engenharia Química Faculty of Engineering University of Porto Porto 4200‐465 Portugal

  13. Miguel Dias Castilho corresponding

    Utrecht University · University Medical Center Utrecht · Eindhoven University of Technology

    Affiliation as printed

    Department of Biomedical Engineering Eindhoven University of Technology Eindhoven 5612 AE The Netherlands

    Department of Orthopaedics Regenerative Medicine Center Utrecht University Medical Center Utrecht Utrecht 3508 GA The Netherlands

    Institute for Complex Molecular Systems Eindhoven University of Technology Eindhoven 5612 AE The Netherlands

    Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, 5612 AE The Netherlands

    Department of Orthopaedics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, 3508 GA The Netherlands

    Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, 5612 AE The Netherlands

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References 60