Magnetic-Field-Driven Precision Fabrication of Multifunctional Microgels for Biomedical Applications

Abstract

The fabrication of monodisperse microgels has achieved considerable success and has transformed many fields. However, conventional methods typically rely on external shear forces, interfacial perturbations, or toxic solvents, which restrict their application flexibility. This study presents a novel magnetic-field-actuated strategy for fabricating uniform microgels (300-900 µm) with tunable morphologies, including microspheres and microfibers, bypassing the need for external shear forces, interfacial perturbations, or toxic solvents. By integrating superparamagnetic iron oxide nanoparticles (SPIONs) into hydrogel precursors, internal magnetic stress gradients induce self-driven droplet segmentation, enabling precise control over particle size and structure with high-throughput production and exceptional uniformity. These biocompatible microgels exhibit robust magnetic responsiveness, facilitating precise positioning and occlusion in vascular embolism models and enhancing toxin clearance in hemodialysis by three to four times through turbulence induced by magnetically driven rotation. This magnetically programmable platform merges microgel synthesis and functionalization, offering a versatile class of carriers with adaptable structures for regenerative medicine and precision medicine applications.

Keywords

hemodialysis / magnetic field / microgels / SPIONs / vascular embolism

References

[1] L. Xuan, Y. Hou, L. Liang, et al., “Microgels for Cell Delivery in Tissue Engineering and Regenerative Medicine,” Nano-Micro Letters 16 (2024): 218.

[2] Z. Liu, J. Wu, Z. Luo, et al., “3D Biofabrication of Microporous Hydrogels for Tissue Engineering,” Advanced Healthcare Materials 14 (2025): e2403583.

[3] Y. Hou, L. Xuan, W. Mo, et al., “Anisotropic Microcarriers: Fabrication Strategies and Biomedical Applications,” Advanced Materials 37 (2025): 2416862.

[4] G. Tang, R. Xiong, D. Lv, et al., “Gas-Shearing Fabrication of Multicompartmental Microspheres: A One-Step and Oil-Free Approach,” Advanced Science 6 (2019): 1802342.

[5] T. Moragues, D. Arguijo, T. Beneyton, et al., “Droplet-Based Microfluidics,” Nature Reviews Methods Primers 3 (2023): 32.

[6] I. Yoon, A. Shum, and L. D. H. D. Weitz, “Fabrication of phospholipid vesicles from double emulsions in microfluidics,” Bulletin of the American Physical Society 53, Abstract X8.00007, p. 50 (2008), http://meetings.aps.org/link/BAPS.2008.MAR.X8.7.

[7] L.-Y. Chu, A. Utada, R. Shah, J. W. Kim, and D. Weitz, “Controllable Monodisperse Multiple Emulsions,” Angewandte Chemie International Edition 46 (2007): 8970-8974.

[8] H. Kim, D. Luo, D. Link, D. Weitz, M. Marquez, and Z. Cheng, “Controlled Production of Emulsion Drops Using an Electric Field in a Flow-Focusing Microfluidic Device,” Applied Physics Letters 91 (2007): 133106.

[9] Q. Feng, D. Li, Q. Li, X. Cao, and H. Dong, “Microgel Assembly: Fabrication, Characteristics and Application in Tissue Engineering and Regenerative Medicine,” Bioactive Materials 9 (2022): 105.

[10] Q. Feng, D. Li, Q. Li, et al., “Assembling Microgels via Dynamic Cross-Linking Reaction Improves Printability, Microporosity, Tissue-Adhesion, and Self-Healing of Microgel Bioink for Extrusion Bioprinting,” ACS Applied Materials & Interfaces 14 (2022): 15653.

[11] Z. Chen, Z. Lv, Z. Zhang, et al., “Advanced Microfluidic Devices for Fabricating Multi-Structural Hydrogel Microsphere,” Exploration 1 (2021): 20210036.

[12] Y. Xu, H. Zhu, A. Denduluri, et al., “Recent Advances in Microgels: From Biomolecules to Functionality,” Small 18 (2022): 2200180.

[13] S. Deng, W. Shang, S. Feng, et al., “Controlled Droplet Transport to Target on a High Adhesion Surface With Multi-Gradients,” Scientific Reports 7 (2017): 45687.

[14] L. Wu, Z. Dong, F. Li, and Y. Song, “Designing Laplace Pressure Pattern for Microdroplet Manipulation,” Langmuir 34 (2018): 639.

[15] M. C. Mendes, J. A. Pereira, A. S. Silva, and J. F. Mano, “Magneto-Enzymatic Microgels for Precise Hydrogel Sculpturing,” Advanced Materials 36 (2024): 2402988.

[16] B. Kong, R. Liu, J. Guo, L. Lu, Q. Zhou, and Y. Zhao, “Tailoring Micro/Nano-Fibers for Biomedical Applications,” Bioactive Materials 19 (2023): 328-347.

[17] C. Zhou, C. Wang, K. Xu, et al., “Hydrogel Platform With Tunable Stiffness Based on Magnetic Nanoparticles Cross-Linked GelMA for Cartilage Regeneration and Its Intrinsic Biomechanism,” Bioactive Materials 25 (2023): 615-628.

[18] S. Ganguly and S. Margel, “3D Printed Magnetic Polymer Composite Hydrogels for Hyperthermia and Magnetic Field Driven Structural Manipulation,” Progress in Polymer Science 131 (2022): 101574.

[19] E. M. Greeson, C. S. Madsen, A. V. Makela, and C. H. Contag, “Magnetothermal Control of Temperature-Sensitive Repressors in Superparamagnetic Iron Nanoparticle-Coated Bacillus subtilis,” ACS Nano 16 (2022): 16699.

[20] Z. Ding, Y. Cai, H. Sun, et al., “Janus Hydrogel Microrobots With Bioactive Ions for the Regeneration of Tendon-Bone Interface,” Nature Communications 16 (2025): 2189.

[21] H. Wang, Y. Hou, L. Chen, et al., “Superparamagnetic Hydrogels: Precision-Driven Platforms for Biomedicine, Robotics, and Environmental Remediation,” Biomedical Technology 10 (2025): 100084.

[22] X. He, Y. He, G. Wen, and F. Jiao, “Evolution and Breakup of a Ferrofluid Droplet Neck Through a Capillary Tube,” Chemical Engineering Science 289 (2024): 119882.

[23] R. E. Rosenweig, Ferrohydrodynamics (Cambridge University Press, 1985).

[24] A. P. Stikuts, R. Perzynski, and A. Cēbers, “Small Deformation Theory for a Magnetic Droplet in a Rotating Field,” Physics of Fluids 34 (2022): 052010.

[25] K. Xu, C. P. Tostado, J.-H. Xu, Y.-C. Lu, and G.-S. Luo, “Direct Measurement of the Differential Pressure During Drop Formation in a Co-Flow Microfluidic Device,” Lab on a Chip 14 (2014): 1357.

[26] B. T. Helenbrook and C. F. Edwards, “Quasi-Steady Deformation and Drag of Uncontaminated Liquid Drops,” International Journal of Multiphase Flow 28 (2002): 1631.

[27] L. Shao, B. Pan, R. Hou, Y. Jin, and Y. Yao, “User-Friendly Microfluidic Manufacturing of Hydrogel Microspheres With Sharp Needle,” Biofabrication 14 (2022): 025017.

[28] W. J. Seeto, Y. Tian, S. Pradhan, P. Kerscher, and E. A. Lipke, “Rapid Production of Cell-Laden Microspheres Using a Flexible Microfluidic Encapsulation Platform,” Small 15 (2019): 1902058.

[29] C. Zhang, R. Grossier, L. Lacaria, F. Rico, N. Candoni, and S. Veesler, “A Microfluidic Method Generating Monodispersed Microparticles With Controllable Sizes and Mechanical Properties,” Chemical Engineering Science 211 (2020): 115322.

[30] K. Danas, S. V. Kankanala, and N. Triantafyllidis, “Experiments and Modeling of Iron-Particle-Filled Magnetorheological Elastomers,” Journal of the Mechanics and Physics of Solids 60 (2012): 120-138.

[31] D. Wang and W. Rao, “Bench-to-Bedside Development of Multifunctional Flexible Embolic Agents,” Theranostics 13 (2023): 2114.

[32] H. Wu, S. Lv, R. Zhang, et al., “Next-Generation Flexible Embolic Systems: Targeted Transarterial Chemoembolization Strategies for Hepatocellular Carcinoma,” Advanced Materials 37 (2025): 2503971.

[33] S. Yu, X. Yan, C. Wang, et al., “A Non-invasive, Closed-Loop Electronic Stent for Real-Time Management of Gastroesophageal Reflux Disease,” Advanced Fiber Materials 8 (2026): 289-302.

[34] J. Luo, J. B. Fan, and S. Wang, “Recent Progress of Microfluidic Devices for Hemodialysis,” Small 16 (2020): 1904076.

[35] H. Zhang, X. Han, J. Liu, et al., “Fabrication of Modified Alginate-Based Biocomposite Hydrogel Microspheres for Efficient Removal of Heavy Metal Ions From Water,” Colloids and Surfaces A: Physicochemical and Engineering Aspects 651 (2022): 129736.

[36] J. Zhao, H. Li, C. Mu, S. Zhang, F. Shi, and J. Hu, “Performance and Mechanism of L-Arginine Modified Alginate Aerogels for Adsorption of Cadmium and Copper Ions,” Journal of Polymers and the Environment 32 (2024): 5086-5097.

[37] D. S. Veliz, K. L. Lin, and C. Sahlgren, “Organ-on-a-Chip Technologies for Biomedical Research and Drug Development: A Focus on the Vasculature,” Smart Medicine 2 (2023): e20220030.

[38] J. Law, X. Wang, M. Luo, et al., “Microrobotic Swarms for Selective Embolization,” Science Advances 8 (2022): eabm5752.

[39] D. Jin, Q. Wang, K. F. Chan, et al., “Swarming Self-Adhesive Microgels Enabled Aneurysm on-Demand Embolization in Physiological Blood Flow,” Science Advances 9 (2023): eadf9278.

[40] X. Liu, L. Wang, Y. Xiang, et al., “Magnetic Soft Microfiberbots for Robotic Embolization,” Science Robotics 9 (2024): eadh2479.

RIGHTS & PERMISSIONS

2026 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.