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Microsystem Technologies

, Volume 24, Issue 7, pp 2905–2912 | Cite as

Cell therapy using an array of ultrathin hollow microneedles

  • Florina Silvia Iliescu
  • Jeremy Choon Meng Teo
  • Danilo Vrtacnik
  • Hayden Taylor
  • Ciprian IliescuEmail author
Technical Paper

Abstract

Cell transplantation traditionally employs needles to inject donor cells into tissues to treat certain diseases. However, it is difficult for the current method to achieve multiple parallel equidistant injections, which are ideal for cell therapy. This paper presents a new cell transplantation method using an array of ultrathin microneedles. The main characteristic of the needles is their high aspect ratio: each needle is 500 μm long, and has a 50 μm diameter and a very thin wall (2 μm-thick SiO2 and 1.5 μm-thick Si3N4). An array of such microneedles was successfully used to inject fluorescently labeled Mardin–Darby canine kidney cells into rat liver tissue. Viability of the cells inserted using this method was verified after 5 days. Preliminary results show that this type of microneedle array can be used for cell therapy.

References

  1. Alhasan L, Qi A, Al-Abboodi A, Rezk A, Chan PP, Iliescu C, Yeo LY (2016) Rapid enhancement of cellular spheroid assembly by acoustically driven microcentrifugation. ACS Biomater Sci Eng 2:1013–1022CrossRefGoogle Scholar
  2. Avram A et al (2014) Fabrication of thin dielectric membranes for microwave applications. Dig J Nanomater Biostruct 9:475–481Google Scholar
  3. Beißner N, Lorenz T, Reichl S (2016) Organ on chip. In: Microsystems for pharmatechnology. Springer, New York, pp 299–339Google Scholar
  4. Chen B, Wei J, Tay FE, Wong YT, Iliescu C (2008) Silicon microneedle array with biodegradable tips for transdermal drug delivery. Microsyst Technol 14:1015–1019CrossRefGoogle Scholar
  5. Chen B, Wei J, Iliescu C (2010) Sonophoretic enhanced microneedles array (SEMA)—improving the efficiency of transdermal drug delivery. Sens Actuators B Chem 145:54–60CrossRefGoogle Scholar
  6. Cima I, Wen Yee C, Iliescu FS, Min Phyo W, Hon Lim K, Iliescu C, Han Tan M (2013) Label-free isolation of circulating tumor cells in microfluidic devices: current research and perspectives. Biomicrofluidics 7:011810CrossRefGoogle Scholar
  7. Duffield JS, Park KM, Hsiao L-L, Kelley VR, Scadden DT, Ichimura T, Bonventre JV (2005) Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J Clin Investig 115:1743CrossRefGoogle Scholar
  8. Esch EW, Bahinski A, Huh D (2015) Organs-on-chips at the frontiers of drug discovery. Nat Rev Drug Discov 14:248CrossRefGoogle Scholar
  9. Gojo S et al (2003) In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells. Exp Cell Res 288:51–59CrossRefGoogle Scholar
  10. Griffith LG, Naughton G (2002) Tissue engineering—current challenges and expanding opportunities. Science 295:1009–1014CrossRefGoogle Scholar
  11. Griss P, Stemme G (2003) Side-opened out-of-plane microneedles for microfluidic transdermal liquid transfer. J Microelectromech Syst 12:296–301CrossRefGoogle Scholar
  12. Henry S, McAllister DV, Allen MG, Prausnitz MR (1998) Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci 87:922–925CrossRefGoogle Scholar
  13. Iliescu C, Tresset G (2015) Microfluidics-driven strategy for size-controlled DNA compaction by slow diffusion through water stream. Chem Mater 27:8193–8197CrossRefGoogle Scholar
  14. Iliescu C, Tay FE, Wei J (2006) Low stress PECVD—SiNx layers at high deposition rates using high power and high frequency for MEMS applications. J Micromech Microeng 16:869CrossRefGoogle Scholar
  15. Iliescu C, Tresset G, Xu G (2007) Continuous field-flow separation of particle populations in a dielectrophoretic chip with three dimensional electrodes. Appl Phys Lett 90:234104CrossRefGoogle Scholar
  16. Iliescu C et al (2011) Residual stress in thin films PECVD depositions. J Optoelectron Adv Mater 13:387–394Google Scholar
  17. Iliescu FS, Sterian AP, Petrescu M (2013) A parallel between transdermal drug delivery and microtechnology. Univ Politech Buchar Sci Bull Ser A Appl Math Phys 75:227–236Google Scholar
  18. Kochhar JS, Anbalagan P, Shelar SB, Neo JK, Iliescu C, Kang L (2014) Direct microneedle array fabrication off a photomask to deliver collagen through skin. Pharm Res 31:1724–1734CrossRefGoogle Scholar
  19. Kubo K, Tsukasa N, Uehara M, Izumi Y, Ogino M, Kitano M, Sueda T (1997) Calcium and silicon from bioactive glass concerned with formation of nodules in periodontal-ligament fibroblasts in vitro. J Oral Rehabil 24:70–75CrossRefGoogle Scholar
  20. Lanza R, Langer R, Vacanti JP (2014) Principles of tissue engineering, 4th edn. Academic Press, BostonGoogle Scholar
  21. Larrañeta E, Lutton RE, Woolfson AD, Donnelly RF (2016a) Microneedle arrays as transdermal and intradermal drug delivery systems: materials science, manufacture and commercial development. Mater Sci Eng R Rep 104:1–32CrossRefGoogle Scholar
  22. Larrañeta E, McCrudden MTC, Courtenay AJ, Donnelly RF (2016b) Microneedles: a new frontier in nanomedicine delivery. Pharm Res 33:1055–1073.  https://doi.org/10.1007/s11095-016-1885-5 CrossRefGoogle Scholar
  23. Lee W, Tseng P, Di Carlo D (eds) (2017) Microfluidic cell sorting and separation technology. In: Microtechnology for cell manipulation and sorting. Microsystems and Nanosystems. Springer, ChamGoogle Scholar
  24. Lim SH, Ng JY, Kang L (2017) Three-dimensional printing of a microneedle array on personalized curved surfaces for dual-pronged treatment of trigger finger. Biofabrication 9:015010CrossRefGoogle Scholar
  25. Lin L, Pisano AP (1999) Silicon-processed microneedles. J Microelectromech Syst 8:78–84CrossRefGoogle Scholar
  26. Liu D, Zhang H, Fontana F, Hirvonen JT, Santos HA (2017) Microfluidic-assisted fabrication of carriers for controlled drug delivery. Lab Chip 17:1856–1883CrossRefGoogle Scholar
  27. Lu M, Ozcelik A, Grigsby CL, Zhao Y, Guo F, Leong KW, Huang TJ (2016) Microfluidic hydrodynamic focusing for synthesis of nanomaterials. Nano Today 11:778–792CrossRefGoogle Scholar
  28. Müller A et al (2001) Micromachined filters for 38 and 77 GHz supported on thin membranes. J Micromech Microeng 11:301CrossRefGoogle Scholar
  29. Nayak A, Babla H, Han T, Das DB (2016) Lidocaine carboxymethylcellulose with gelatine co-polymer hydrogel delivery by combined microneedle and ultrasound. Drug Deliv 23:658–669CrossRefGoogle Scholar
  30. Ni M, Tong WH, Choudhury D, Rahim NAA, Iliescu C, Yu H (2009) Cell culture on MEMS platforms: a review. Int J Mol Sci 10:5411–5441CrossRefGoogle Scholar
  31. Ni M, Tresset G, Iliescu C (2017) Self-assembled polysulfone nanoparticles using microfluidic chip. Sens Actuators B Chem 252:458–462CrossRefGoogle Scholar
  32. Ohashi K et al (2007) Engineering functional two-and three-dimensional liver systems in vivo using hepatic tissue sheets. Nat Med 13:880–886CrossRefGoogle Scholar
  33. Park J-H, Allen MG, Prausnitz MR (2005) Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J Control Release 104:51–66CrossRefGoogle Scholar
  34. Quimby J, Dow S (2015) Novel treatment strategies for feline chronic kidney disease: a critical look at the potential of mesenchymal stem cell therapy. Vet J 204:241–246CrossRefGoogle Scholar
  35. Resnik D, Možek M, Pečar B, Dolžan T, Janež A, Urbančič V, Vrtačnik D (2015) Characterization of skin penetration efficacy by Au-coated Si microneedle array electrode. Sens Actuators A 232:299–309CrossRefGoogle Scholar
  36. Roda A et al (2016) Progress in chemical luminescence-based biosensors: a critical review. Biosens Bioelectron 76:164–179CrossRefGoogle Scholar
  37. Sanjay ST, Zhou W, Dou M, Tavakoli H, Ma L, Xu F, Li X (2017) Recent advances of controlled drug delivery using microfluidic platforms. Adv Drug Deliv Rev (in press)Google Scholar
  38. Skuk D, Tremblay JP (2003) Myoblast transplantation: the current status of a potential therapeutic tool for myopathies. J Muscle Res Cell Motil 24:287–302CrossRefGoogle Scholar
  39. Stoeber B, Liepmann D (2005) Arrays of hollow out-of-plane microneedles for drug delivery. J Microelectromech Syst 14:472–479CrossRefGoogle Scholar
  40. Tong WH et al (2016) Constrained spheroids for prolonged hepatocyte culture. Biomaterials 80:106–120CrossRefGoogle Scholar
  41. Tuan-Mahmood T-M, McCrudden MT, Torrisi BM, McAlister E, Garland MJ, Singh TRR, Donnelly RF (2013) Microneedles for intradermal and transdermal drug delivery. Eur J Pharm Sci 50:623–637CrossRefGoogle Scholar
  42. Yu F, Zhuo S, Qu Y, Choudhury D, Wang Z, Iliescu C, Yu H (2017) On chip two-photon metabolic imaging for drug toxicity testing. Biomicrofluidics 11:034108CrossRefGoogle Scholar
  43. Zhang S et al (2011) A robust high-throughput sandwich cell-based drug screening platform. Biomaterials 32:1229–1241CrossRefGoogle Scholar
  44. Zhou Y, Tang L, Zeng G, Zhang C, Zhang Y, Xie X (2016) Current progress in biosensors for heavy metal ions based on DNAzymes/DNA molecules functionalized nanostructures: a review. Sens Actuators B Chem 223:280–294CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.School of Applied ScienceRepublic PolytechnicSingaporeSingapore
  2. 2.Department of Biomedical EngineeringKhalifa University of Science and TechnologyAbu DhabiUnited Arab Emirates
  3. 3.Laboratory of Microsensor Structures and Electronics, Faculty of Electrical EngineeringUniversity of LjubljanaLjubljanaSlovenia
  4. 4.Department of Mechanical EngineeringUniversity of California, BerkeleyBerkeleyUSA
  5. 5.National Institute for Research and Development in Microtechnologies, IMT-BucharestBucharestRomania
  6. 6.Academy of Romanian ScientistsBucharestRomania

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