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Polymeric Soft Micro-Robots Propelled into a Microfluidic Device for Gut Target Delivery Studies

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Design Tools and Methods in Industrial Engineering III (ADM 2023)

Part of the book series: Lecture Notes in Mechanical Engineering ((LNME))

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Abstract

Soft microrobots have gained great attention in the bioengineering field due to their ability to navigate into biological fluids, overcoming biological barriers. Indeed, thanks to the size and controlled movement they can easily deliver drugs to a specific target.

In this work, we present completely natural and biodegradable propulsion soft micro-robots made of alginate, in the shape of microparticles (MPs). These MPs have been loaded with sodium bicarbonate and are meant to be delivered together with citric acid as a powder-based formulation embedded into a capsule that will open in the gut. Sodium carbonate released from MPs allows a propulsive action due to the citric acid spherical gradient established upon its release, making MPs go radially toward the gut mucosa. In principle, MPs can be loaded with anti-inflammatory drugs or probiotics allowing a slow release of the compound close to the cell layer. The action of such micro-robots was tested inside a microfluidic device that recreated citric acid gradient, with a channel for the introduction of MPs. Here we saw the propulsion activity of MPs towards lower citric acid concentration by taking time-lapse images. Caco-2 cells were cultured in the same microfluidic device allowing the formation of a mucus-like layer to assess the accumulation of the propulsive MPs.

R. Crispiano and B. Corrado—These authors contributed equally to this work.

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References

  1. Nelson, B.J., Kaliakatsos, I.K. Abbott, J.J.: Microrobots for minimally invasive medicine, Annu. Rev. Biomed. Eng., 12(1), 55–85 (2010). https://doi.org/10.1146/annurev-bioeng-010510-103409

  2. Huang, T.Y., et al.: 3D printed microtransporters: compound micromachines for spatiotemporally controlled delivery of therapeutic agents, Adv. Mater., 27(42), 6644–6650 (2015). https://doi.org/10.1002/adma.201503095

  3. Ahmed, D., Dillinger, C., Hong, A., Nelson, B.J.: Artificial acousto-magnetic soft microswimmers, Adv. Mater. Technol. 2(7), 1700050 (2017). https://doi.org/10.1002/admt.201700050

  4. Palagi, S., Singh, D.P., Fischer, P.: Light‐controlled micromotors and soft microrobots, Adv. Opt. Mater. 7(16), 1900370 (2019). https://doi.org/10.1002/adom.201900370

  5. Medina-Sánchez, M., Magdanz, V., Guix, M., Fomin, V.M., Schmidt, O.G.: Swimming microrobots: soft, reconfigurable, and smart, Adv. Funct. Mater. 28(25), 1707228, (2018). https://doi.org/10.1002/adfm.201707228

  6. Nocentini, S., Parmeggiani, C., Martella, D., Wiersma, D.S.: Optically Driven Soft Micro Robotics, Adv. Opt. Mater. 6(14), 1800207 (2018). https://doi.org/10.1002/adom.201800207

  7. Mair, L.O., et al.: Soft capsule magnetic millirobots for region-specific drug delivery in the central nervous system, Front. Robot. AI, 8, 702566 (2021). https://doi.org/10.3389/frobt.2021.702566

  8. Lee, H., Choi, H., Lee, M., Park, S.: Preliminary study on alginate/NIPAM hy-drogel-based soft microrobot for controlled drug delivery using electromagnetic actuation and near-infrared stimulus», Biomed. Microdevices, 20(4), 103 (2018). https://doi.org/10.1007/s10544-018-0344-y

  9. Power, M., Anastasova, S., Shanel, S., Yang, G.Z.: Towards hybrid micro-robots using pH- and photo-responsive hydrogels for cancer targeting and drug delivery. In: 2017 IEEE International Conference on Robotics and Automation (ICRA), Singapore, Singapore: IEEE, mag, pp. 6002–6007 (2017). https://doi.org/10.1109/ICRA.2017.7989709

  10. Li, T., Li, L., Song, W., Wang, L., Shao, G., Zhang, G.: Self-Propelled multi-layered microrockets for pollutants purification, ECS J. Solid State Sci. Technol. 4(10), S3016–S3019 (2015). https://doi.org/10.1149/2.0041510jss

  11. Baylis, J.R., et al.: Self-propelled particles that transport cargo through flowing blood and halt hemorrhage, Sci. Adv., 1(9), e1500379, (2015). https://doi.org/10.1126/sciadv.1500379

  12. Sun, H.C.M., Liao, P., Wei, T., Zhang, L., Sun, D.: Magnetically powered bio-degradable microswimmers, Micromachines, 11(4), 404 (2020). https://doi.org/10.3390/mi11040404

  13. Wang, X., et al.: 3D printed enzymatically biodegradable soft helical micro-swimmers», Adv. Funct. Mater. 28(45), 1804107 (2018). https://doi.org/10.1002/adfm.201804107

  14. Park, J., Kim, J., Pané, S., Nelson, B.J., Choi, H.: Acoustically mediated controlled drug release and targeted therapy with degradable 3D porous magnetic microrobots, Adv. Healthc. Mater. 10(2), 2001096 (2021). https://doi.org/10.1002/adhm.202001096

  15. Louis, F., et al.: Bioprinted Vascularized Mature Adipose Tissue with Collagen Microfibers for Soft Tissue Regeneration, Cyborg Bionic Syst. 2021/1412542, (2021). https://doi.org/10.34133/2021/1412542

  16. Zhong, D., et al.: Orally deliverable strategy based on microalgal biomass for intestinal disease treatment, Sci. Adv., 7(48), eabi9265 (2021). https://doi.org/10.1126/sciadv.abi9265

  17. Quashie, D., et al.: Magnetic bio-hybrid micro actuators, Nanoscale, 14(12), 4364–4379 (2022). https://doi.org/10.1039/D2NR00152G

  18. Yasa, O., Erkoc, P., Alapan, Y., Sitti, M.: Microalga-powered microswimmers toward active cargo delivery, Adv. Mater., 30(45) 1804130 (2018). https://doi.org/10.1002/adma.201804130

  19. Lee, K.Y., Mooney, D.J.: Alginate: Properties and biomedical applications, Prog. Polym. Sci., 37(1), 106–126 (2012). https://doi.org/10.1016/j.progpolymsci.2011.06.003

  20. Yin, B.S., Li, M., Liu, B.M., Wang, S.Y., Zhang, W.G.: An integrated micro-fluidic device for screening the effective concentration of locally applied tacro-limus for peripheral nerve regeneration, Exp. Ther. Med. 9 (1) 154–158, (2015). https://doi.org/10.3892/etm.2014.2082

  21. Di Natale, C., et al.: Morphological and rheological guided design for the microencapsulation process of lactobacillus paracasei CBA L74 in calcium alginate microspheres, Front. Bioeng. Biotechnol. 9, 660691 (2021). https://doi.org/10.3389/fbioe.2021.660691

  22. Norouzi, A.R., Nikfarjam, A., Hajghassem, H.: PDMS–PMMA bonding improvement using SiO2 intermediate layer and its application in fabricating gas micro valves, Microsyst. Technol. 24(6), 2727–2736, (2018). https://doi.org/10.1007/s00542-017-3676-2

  23. Müller, G.T.A., Stokes, R.H.: The mobility of the undissociated citric acid molecule in aqueous solution, Trans Faraday Soc, 53, 642–645 (1957) https://doi.org/10.1039/TF9575300642

  24. Fujii, T.: PDMS-based microfluidic devices for biomedical applications, Microelectron. Eng., 61, 907–914 (2002). https://doi.org/10.1016/S0167-9317(02)00494-X

  25. Liga, A., Morton, J.A.S., Kersaudy-Kerhoas, M.: Safe and cost-effective rap-id-prototyping of multilayer PMMA microfluidic devices, Microfluid. Nanofluidics, 20(12), 164 (2016). https://doi.org/10.1007/s10404-016-1823-1

  26. Zimmerman, W.B.J.: Multiphysics Modeling with Finite Element Methods, vol. 18. Series on Stability, Vibration and Control of Systems, Series A, vol. 18. WORLD SCIENTIFIC (2006). https://doi.org/10.1142/6141

  27. Lentle, R.G., Janssen, P.W.M., Physical characteristics of digesta and their influence on flow and mixing in the mammalian intestine: a review, J. Comp. Physiol. B, 178(6), 673–690 (2008). https://doi.org/10.1007/s00360-008-0264-x

  28. De Gregorio, V. et al.: Intestine‐on‐chip device increases ECM remodeling inducing faster epithelial cell differentiation, Biotechnol. Bioeng. 117(2), 556–566 (2020). https://doi.org/10.1002/bit.27186

  29. Beckwitt, C.H., et al.: Liver ‘organ on a chip’, Exp. Cell Res. 363(1) 15–25, (2018). https://doi.org/10.1016/j.yexcr.2017.12.023

  30. Zhang, Y.S. et al.: From cardiac tissue engineering to heart-on-a-chip: beating challenges, Biomed. Mater. 10(3). 034006 (2015), https://doi.org/10.1088/1748-6041/10/3/034006

  31. Mazio, C. et al.: Easy-to-build and reusable microfluidic device for the dynamic culture of human bronchial cystic fibrosis epithelia, ACS Biomater. Sci. Eng. 9(5), 2780–2792 (2023). https://doi.org/10.1021/acsbiomaterials.2c01460

  32. Ashammakhi, N., Wesseling-Perry, K., Hasan, A., Elkhammas, E., Zhang, Y.S.: Kidney-on-a-chip: untapped opportunities», Kidney Int., 94(6), 1073–1086 (2018). https://doi.org/10.1016/j.kint.2018.06.034

  33. Griep, L.M., et al.: BBB ON CHIP: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function», Biomed. Microdevices, 15(1), 145–150 (2013). https://doi.org/10.1007/s10544-012-9699-7

  34. Xu, J., Wu, T., Zhang, Y.: Soft microrobots in microfluidic applications, Biomed. Mater. Devices, 1(2), (2023). https://doi.org/10.1007/s44174-023-00071-2

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Authors and Affiliations

  1. Istituto Italiano di Tecnologia, Naples, Italy

    Raffaele Crispino, Raffaele Vecchione & Paolo Antonio Netti

  2. Department of Chemical Materials, Industrial Production Engineering, University of Naples Federico II, Naples, Italy

    Raffaele Crispino, Brunella Corrado & Paolo Antonio Netti

  3. Interdisciplinary Research Centre on Biomaterials, University of Naples Federico II, Naples, Italy

    Brunella Corrado & Paolo Antonio Netti

Authors
  1. Raffaele Crispino
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  2. Brunella Corrado
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  3. Raffaele Vecchione
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  4. Paolo Antonio Netti
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Correspondence to Raffaele Vecchione .

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Editors and Affiliations

  1. Department of Industrial Engineering, University of Florence, Florence, Italy

    Monica Carfagni

  2. Department of Industrial Engineering, University of Florence, Florence, Italy

    Rocco Furferi

  3. Department of Industrial and Information Engineering and Economics, University of L'Aquila, L’Aquila, Italy

    Paolo Di Stefano

  4. Department of Industrial Engineering, University of Florence, Florence, Italy

    Lapo Governi

  5. Department of Engineering "Enzo Ferrari", University of Modena and Reggio Emilia, Modena, Italy

    Francesco Gherardini

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Crispino, R., Corrado, B., Vecchione, R., Netti, P.A. (2024). Polymeric Soft Micro-Robots Propelled into a Microfluidic Device for Gut Target Delivery Studies. In: Carfagni, M., Furferi, R., Di Stefano, P., Governi, L., Gherardini, F. (eds) Design Tools and Methods in Industrial Engineering III. ADM 2023. Lecture Notes in Mechanical Engineering. Springer, Cham. https://doi.org/10.1007/978-3-031-58094-9_68

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  • DOI: https://doi.org/10.1007/978-3-031-58094-9_68

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  • Online ISBN: 978-3-031-58094-9

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