Skip to main content

Advertisement

SpringerLink
Log in

On-chip fabrication of magnetic alginate hydrogel microfibers by multilayered pneumatic microvalves

  • Research Paper
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

Abstract

Alginate hydrogel has widespread applications in tissue engineering, cancer therapy, wound management and drug/cell/growth factor delivery due to its biocompatibility, hydrated environment and desirable viscoelastic properties. However, the lack of controllability is still an obstacle for utilizing it in the fabrication of 3D tissue constructs and accurate targeting in mass delivery. Here, we proposed a new method for achieving magnetic alginate hydrogel microfibers by dispersing magnetic nanoparticles in alginate solution and solidifying the magnetic alginate into hydrogel fiber inside microfluidic devices. The microfluidic devices have multilayered pneumatic microvalves with hemicylindrical channels to fully stop the fluids. In the experiments, the magnetic nanoparticles and the alginate solution were mixed and formed a uniform suspension. No aggregation of magnetic nanoparticles was found, which is crucial for flow control inside microfluidic devices. By regulating the flow rates of different solutions with the microvalves inside the microfluidic device, magnetic hydrogel fibers and nonmagnetic hydrogel fibers were fabricated with controlled sizes. The proposed method for fabricating magnetic hydrogel fiber holds great potential for engineering 3D tissue constructs with complex architectures and active drug release.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Aubin H, Nichol JW, Hutson CB, Bae H, Sieminski AL, Cropek DM, Akhyari P, Khademhosseini A (2010) Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials 31(27):6941–6951. doi:10.1016/j.biomaterials.2010.05.056

    Article  Google Scholar 

  • Bako J, Vecsernyes M, Ujhelyi Z, Kovacsne IB, Borbiro I, Biro T, Borbely J, Hegedus C (2013) Composition and characterization of in situ usable light cured dental drug delivery hydrogel system. J Mater Sci Mater Med 24(3):659–666. doi:10.1007/s10856-012-4825-x

    Google Scholar 

  • Barry RA, Shepherd RF, Hanson JN, Nuzzo RG, Wiltzius P, Lewis JA (2009) Direct-write assembly of 3D hydrogel scaffolds for guided cell growth. Adv Mater 21(23):2407–2410. doi:10.1002/adma.200803702

    Article  Google Scholar 

  • Bhatia SR, Khattak SF, Roberts SC (2005) Polyelectrolytes for cell encapsulation. Curr Opin Colloid Interface 10(1–2):45–51. doi:10.1016/j.cocis.2005.05.004

    Article  Google Scholar 

  • Cheng Y, Luo X, Tsao C-Y, Wu H-C, Betz J, Payne GF, Bentley WE, Rubloff GW (2011) Biocompatible multi-address 3D cell assembly in microfluidic devices using spatially programmable gel formation. Lab Chip 11(14):2316–2318

    Article  Google Scholar 

  • Choi NW, Cabodi M, Held B, Gleghorn JP, Bonassar LJ, Stroock AD (2007) Microfluidic scaffolds for tissue engineering. Nat Mater 6(11):908–915. doi:10.1038/Nmat2022

    Google Scholar 

  • Cushing MC, Anseth KS (2007) Hydrogel cell cultures. Science 316(5828):1133–1134. doi:10.1126/science.1140171

    Article  Google Scholar 

  • Du YA, Lo E, Ali S, Khademhosseini A (2008) Directed assembly of cell-laden microgels for fabrication of 3D tissue constructs. Proc Natl Acad Sci USA 105(28):9522–9527. doi:10.1073/pnas.0801866105

    Article  Google Scholar 

  • Fedorovich NE, Alblas J, de Wijn JR, Hennink WE, Verbout AJ, Dhert WJA (2007) Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the-art and novel application in organ printing. Tissue Eng 13(8):1905–1925. doi:10.1089/ten.2006.0175

    Article  Google Scholar 

  • Galateanu B, Dimonie D, Vasile E, Nae S, Cimpean A, Costache M (2012) Layer-shaped alginate hydrogels enhance the biological performance of human adipose-derived stem cells. Bmc Biotechnol 12. doi:10.1186/1472-6750-12-35

  • Giri TK, Thakur D, Alexander A, Ajazuddin HB, Tripathi DK (2012) Alginate based hydrogel as a potential biopolymeric carrier for drug delivery and cell delivery systems: present status and applications. Curr Drug Deliv 9(6):539–555

    Article  Google Scholar 

  • Han N, Johnson J, Lannutti JJ, Winter JO (2012) Hydrogel-electrospun fiber composite materials for hydrophilic protein release. J Controlled Release 158(1):165–170. doi:10.1016/j.jconrel.2011.09.094

    Article  Google Scholar 

  • Hu M, Deng R, Schumacher KM, Kurisawa M, Ye H, Purnamawati K, Ying JY (2010) Hydrodynamic spinning of hydrogel fibers. Biomaterials 31(5):863–869. doi:10.1016/j.biomaterials.2009.10.002

    Article  Google Scholar 

  • Hu C, Uchida T, Tercero C, Ikeda S, Ooe K, Fukuda T, Arai F, Negoro M, Kwon G (2012) Development of biodegradable scaffolds based on magnetically guided assembly of magnetic sugar particles. J Biotechnol 159(1–2):90–98. doi:10.1016/j.jbiotec.2012.02.002

    Article  Google Scholar 

  • Ko DY, Shinde UP, Yeon B, Jeong B (2013) Recent progress of in situ formed gels for biomedical applications. Prog Polym Sci 38(3–4):672–701. doi:10.1016/j.progpolymsci.2012.08.002

    Article  Google Scholar 

  • Ling Y, Rubin J, Deng Y, Huang C, Demirci U, Karp JM, Khademhosseini A (2007) A cell-laden microfluidic hydrogel. Lab Chip 7(6):756–762. doi:10.1039/B615486g

    Article  Google Scholar 

  • Liu Y, Ramanath HS, Wang DA (2008) Tendon tissue engineering using scaffold enhancing strategies. Trends Biotechnol 26(4):201–209. doi:10.1016/j.tibtech.2008.01.003

    Article  Google Scholar 

  • Liu HX, Wang CY, Gao QX, Chen JX, Ren BY, Liu XX, Tong Z (2009) Facile fabrication of well-defined hydrogel beads with magnetic nanocomposite shells. Int J Pharm 376(1–2):92–98. doi:10.1016/j.ijpharm.2009.04.031

    Google Scholar 

  • Liu JP, Zhang LL, Yang ZH, Zhao XJ (2011) Controlled release of paclitaxel from a self-assembling peptide hydrogel formed in situ and antitumor study in vitro. Int J Nanomed 6:2143–2153. doi:10.2147/Ijn.S24038

    Article  Google Scholar 

  • Liu J, Shi J, Jiang L, Zhang F, Wang L, Yamamoto S, Takano M, Chang M, Zhang H, Chen Y (2012) Segmented magnetic nanofibers for single cell manipulation. Appl Surf Sci 258(19):7530–7535. doi:10.1016/j.apsusc.2012.04.077

    Google Scholar 

  • Man Y, Wang P, Guo YW, Xiang L, Yang Y, Qu YL, Gong P, Deng L (2012) Angiogenic and osteogenic potential of platelet-rich plasma and adipose-derived stem cell laden alginate microspheres. Biomaterials 33(34):8802–8811. doi:10.1016/j.biomaterials.2012.08.054

    Article  Google Scholar 

  • Martel S, Felfoul O, Mathieu JB, Chanu A, Tamaz S, Mohammadi M, Mankiewicz M, Tabatabaei N (2009) MRI-based medical nanorobotic platform for the control of magnetic nanoparticles and flagellated bacteria for target interventions in human capillaries. Int J Robot Res 28(9):1169–1182. doi:10.1177/0278364908104855

    Article  Google Scholar 

  • Massart R, Cabuil V (1987) Effect of some parameters on the formation of colloidal magnetite in alkaline-medium: yield and particle-size control. J Chim Phys Pcb 84(7–8):967–973

    Google Scholar 

  • Nikkhah M, Eshak N, Zorlutuna P, Annabi N, Castello M, Kim K, Dolatshahi-Pirouz A, Edalat F, Bae H, Yang YZ, Khademhosseini A (2012) Directed endothelial cell morphogenesis in micropatterned gelatin methacrylate hydrogels. Biomaterials 33(35):9009–9018. doi:10.1016/j.biomaterials.2012.08.068

    Article  Google Scholar 

  • Nishiyama Y, Nakamura M, Henmi C, Yamaguchi K, Mochizuki S, Nakagawa H, Takiura K (2009) Development of a three-dimensional bioprinter: construction of cell supporting structures using hydrogel and state-of-the-art inkjet technology. J Biomech Eng 131(3):035001. doi:10.1115/1.3002759

    Article  Google Scholar 

  • Ozawa F, Ino K, Arai T, Ramon-Azcon J, Takahashi Y, Shiku H, Matsue T (2013) Alginate gel microwell arrays using electrodeposition for three-dimensional cell culture. Lab Chip 13(15):3128–3135. doi:10.1039/c3lc50455g

    Article  Google Scholar 

  • Pankhurst QA, Connolly J, Jones SK, Dobson J (2003) Applications of magnetic nanoparticles in biomedicine. J Phys D Appl Phys 36(13):R167–R181

    Article  Google Scholar 

  • Pouponneau P, Leroux J-C, Martel S (2009) Magnetic nanoparticles encapsulated into biodegradable microparticles steered with an upgraded magnetic resonance imaging system for tumor chemoembolization. Biomaterials 30(31):6327–6332. doi:10.1016/j.biomaterials.2009.08.005

    Article  Google Scholar 

  • Prinjha R, Moore SE, Vinson M, Blake S, Morrow R, Christie G, Michlovich D, Simmons DL, Walsh FS (2000) Neurobiology: inhibitor of neurite outgrowth in humans. Nature 403(6768):383–384

    Article  Google Scholar 

  • Saboktakin MR, Tabatabaie RM, Maharramov A, Ramazanov MA (2010) Synthesis and characterization of biodegradable chitosan beads as nano-carriers for local delivery of satranidazole. Carbohydr Polym 81(3):726–731. doi:10.1016/j.carbpol.2010.03.047

    Article  Google Scholar 

  • Sakai S, Yamaguchi S, Takei T, Kawakami K (2008) Oxidized alginate-cross-linked alginate/gelatin hydrogel fibers for fabricating tubular constructs with layered smooth muscle cells and endothelial cells in collagen gels. Biomacromolecules 9(7):2036–2041. doi:10.1021/Bm800286v

    Article  Google Scholar 

  • Sugiura S, Szilagyi A, Sumaru K, Hattori K, Takagi T, Filipcsei G, Zrinyi M, Kanamori T (2009) On-demand microfluidic control by micropatterned light irradiation of a photoresponsive hydrogel sheet. Lab Chip 9(2):196–198. doi:10.1039/b810717c

    Article  Google Scholar 

  • Takei T, Sakai S, Ijima H, Kawakami K (2006) Development of mammalian cell-enclosing calcium-alginate hydrogel fibers in a co-flowing stream. Biotechnol J 1(9):1014–1017. doi:10.1002/biot.200600055

    Article  Google Scholar 

  • Willard MA, Kurihara LK, Carpenter EE, Calvin S, Harris VG (2004) Chemically prepared magnetic nanoparticles. Int Mater Rev 49(3–4):125–170. doi:10.1179/095066004225021882

    Article  Google Scholar 

  • Wilson ME, Kota N, Kim Y, Wang YD, Stolz DB, LeDuc PR, Ozdoganlar OB (2011) Fabrication of circular microfluidic channels by combining mechanical micromilling and soft lithography. Lab Chip 11(8):1550–1555. doi:10.1039/C0lc00561d

    Article  Google Scholar 

  • Winkleman A, Bracher PJ, Gitlin I, Whitesides GM (2007) Fabrication and manipulation of ionotropic hydrogels cross-linked by paramagnetic ions. Chem Mat 19(6):1362–1368. doi:10.1021/cm062626f

    Article  Google Scholar 

  • Wohl-Bruhn S, Heim E, Schwoerer A, Bertz A, Harling S, Menzel H, Schilling M, Ludwig F, Bunjes H (2012) Fluxgate magnetorelaxometry: a new approach to study the release properties of hydrogel cylinders and microspheres. Int J Pharm 436(1–2):677–684. doi:10.1016/j.ijpharm.2012.07.021

    Google Scholar 

  • Wu ZL, Gong JP (2011) Hydrogels with self-assembling ordered structures and their functions. Npg Asia Mater 3:57–64. doi:10.1038/asiamat.2010.200

    Article  Google Scholar 

  • Wu ZL, Kurokawa T, Gong JP (2012) Hydrogels with a macroscopic-scale liquid crystal structure by self-assembly of a semi-rigid polyion complex. Polym J 44(6):503–511. doi:10.1038/Pj.2012.74

    Article  Google Scholar 

  • Yang SF, Leong KF, Du ZH, Chua CK (2001) The design of scaffolds for use in tissue engineering. Part 1. Traditional factors. Tissue Eng 7(6):679–689

    Article  Google Scholar 

  • Yao R, Zhang RJ, Lin F, Luan J (2013) Biomimetic injectable HUVEC-adipocytes/collagen/alginate microsphere co-cultures for adipose tissue engineering. Biotechnol Bioeng 110(5):1430–1443. doi:10.1002/Bit.24784

    Article  Google Scholar 

  • Zhao LB, Pan L, Zhang K, Guo SS, Liu W, Wang Y, Chen Y, Zhao XZ, Chan HLW (2009) Generation of Janus alginate hydrogel particles with magnetic anisotropy for cell encapsulation. Lab Chip 9(20):2981–2986. doi:10.1039/B907478c

    Article  Google Scholar 

Download references

Acknowledgments

This work was partially supported by the MEXT KAKENHI Grant No. 23106006 and the COE for Education and Research of Micro-Nano Mechatronics of the Nagoya University Global COE Program. The authors greatly appreciate the help rendered by Hideo Matsuura in the Department of Micro-Nano Systems Engineering, Nagoya University for his help in manufacturing magnetic pillar and his support in the design of the roller for magnetic hydrogel fiber collection.

Author information

Authors and Affiliations

  1. Department of Micro-Nano Systems Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan

    Chengzhi Hu, Masahiro Nakajima, Tao Yue, Masaru Takeuchi & Toshio Fukuda

  2. Department of Applied Chemistry and Biotechnology, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, 263-8522, Japan

    Minoru Seki

  3. School of Mechatronic Engineering, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing, 100-081, China

    Qiang Huang & Toshio Fukuda

Authors
  1. Chengzhi Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masahiro Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tao Yue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masaru Takeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Minoru Seki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toshio Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chengzhi Hu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hu, C., Nakajima, M., Yue, T. et al. On-chip fabrication of magnetic alginate hydrogel microfibers by multilayered pneumatic microvalves. Microfluid Nanofluid 17, 457–468 (2014). https://doi.org/10.1007/s10404-013-1325-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10404-013-1325-3

Keywords

Search

Navigation