Immobilization of INS1E Insulin-Producing Cells Within Injectable Alginate Hydrogels

  • Albert Espona-Noguera
  • Jesús Ciriza
  • Alberto Cañibano-Hernández
  • Laura Saenz del BurgoEmail author
  • Jose Luis PedrazEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 2100)


Alginate has demonstrated high applicability as a matrix-forming biomaterial for cell immobilization due to its ability to make hydrogels combined with cells in a rapid and non-toxic manner in physiological conditions, while showing excellent biocompatibility, preserving immobilized cell viability and function. Moreover, depending on its application, alginate hydrogel physicochemical properties such as porosity, stiffness, gelation time, and injectability can be tuned. This technology has been applied to several cell types that are able to produce therapeutic factors. In particular, alginate has been the most commonly used material in pancreatic islet entrapment for type 1 diabetes mellitus treatment. This chapter compiles information regarding the alginate handling, and we describe the most important steps and recommendations to immobilize insulin-producing cells within a tuned injectable alginate hydrogel using a syringe-based mixing system, detailing how to assess the viability and the biological functionality of the embedded cells.

Key words

Alginate Hydrogel Tissue engineering Diabetes mellitus Controlled drug delivery system Insulin-producing cells 


  1. 1.
    O’Brien FJ (2011) Biomaterials & scaffolds for tissue engineering. Mater Today 14:88–95CrossRefGoogle Scholar
  2. 2.
    Chen F, Liu X (2016) Advancing biomaterials of human origin for tissue engineering. Prog Polym Sci 53:86–168CrossRefGoogle Scholar
  3. 3.
    Kubinova S (2017) Extracellular matrix based biomaterials for central nervous system tissue repair: the benefits and drawbacks. Neural Regen Res 12:1430–1432CrossRefGoogle Scholar
  4. 4.
    Espona-Noguera A, Ciriza J, Cañibano-Hernández A et al (2018) Tunable injectable alginate-based hydrogel for cell therapy in Type 1 diabetes mellitus. Int J Biol Macromol 107:1261–1269CrossRefGoogle Scholar
  5. 5.
    Ahmed EM (2015) Hydrogel: preparation, characterization, and applications: a review. J Adv Res 6:105–121CrossRefGoogle Scholar
  6. 6.
    Hoffman AS (2002) Hydrogels for biomedical applications. Adv Drug Deliv Rev 54:3–12CrossRefGoogle Scholar
  7. 7.
    Buwalda SJ, Vermonden T, Hennink WE (2017) Hydrogels for therapeutic delivery: current developments and future directions. Biomacromolecules 18:316–330CrossRefGoogle Scholar
  8. 8.
    El-Sherbiny IM, Yacoub MH (2013) Hydrogel scaffolds for tissue engineering: progress and challenges. Glob Cardiol Sci Pract 2013:316–342PubMedPubMedCentralGoogle Scholar
  9. 9.
    McMurtrey RJ (2016) Analytic models of oxygen and nutrient diffusion, metabolism dynamics, and architecture optimization in three-dimensional tissue constructs with applications and insights in cerebral organoids. Tissue Eng Part C Methods 22(3):221–249CrossRefGoogle Scholar
  10. 10.
    Zhu J, Marchant RE (2011) Design properties of hydrogel tissue-engineering scaffolds. Expert Rev Med Devices 8:607–626CrossRefGoogle Scholar
  11. 11.
    Howard D, Buttery LD, Shakesheff KM et al (2008) Tissue engineering: strategies, stem cells and scaffolds. J Anat 213:66–72CrossRefGoogle Scholar
  12. 12.
    O'Connor SM, Stenger DA, Shaffer KM et al (2001) Survival and neurite outgrowth of rat cortical neurons in three-dimensional agarose and collagen gel matrices. Neurosci Lett 304(3):189–193CrossRefGoogle Scholar
  13. 13.
    Szot CS, Buchanan CF, Freeman JW et al (2011) 3D in vitro bioengineered tumors based on collagen I hydrogels. Biomaterials 32:7905–7912CrossRefGoogle Scholar
  14. 14.
    Allison DD, Grande-Allen KJ (2006) Review. Hyaluronan: a powerful tissue engineering tool. Tissue Eng 12:2131–2140CrossRefGoogle Scholar
  15. 15.
    Tsou Y, Khoneisser J, Huang P et al (2016) Hydrogel as a bioactive material to regulate stem cell fate. Bioact Mater 1:39–55CrossRefGoogle Scholar
  16. 16.
    Andersen T, Auk-Emblem P, Dornish M (2015) 3D cell culture in alginate hydrogels. Microarrays (Basel) 4(2):133–161CrossRefGoogle Scholar
  17. 17.
    Lee KY, Mooney DJ (2012) Alginate: properties and biomedical applications. Prog Polym Sci 37:106–126CrossRefGoogle Scholar
  18. 18.
    Qi M (2014) Transplantation of encapsulated pancreatic islets as a treatment for patients with type 1 diabetes mellitus. Adv Med 2014:429710CrossRefGoogle Scholar
  19. 19.
    Marchioli G, van Gurp L, van Krieken PP et al (2015) Fabrication of three-dimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation. Biofabrication 7:025009CrossRefGoogle Scholar
  20. 20.
    Bottino R, Trucco M (2015) Clinical implementation of islet transplantation: a current assessment. Pediatr Diabetes 16:393–401CrossRefGoogle Scholar
  21. 21.
    Dimatteo R, Darling NJ, Segura T (2018) In situ forming injectable hydrogels for drug delivery and wound repair. Adv Drug Deliv Rev 127:167–184CrossRefGoogle Scholar
  22. 22.
    O’Sullivan ES, Vegas A, Anderson DG et al (2011) Islets transplanted in immunoisolation devices: a review of the progress and the challenges that remain. Endocr Rev 32:827–844CrossRefGoogle Scholar
  23. 23.
    Krishnan R, Alexander M, Robles L et al (2014) Islet and stem cell encapsulation for clinical transplantation. Rev Diabet Stud 11:84–101CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Albert Espona-Noguera
    • 1
    • 2
  • Jesús Ciriza
    • 1
    • 2
  • Alberto Cañibano-Hernández
    • 1
    • 2
  • Laura Saenz del Burgo
    • 1
    • 2
    Email author
  • Jose Luis Pedraz
    • 1
    • 2
    Email author
  1. 1.NanoBioCel Group, Laboratory of PharmaceuticsSchool of Pharmacy, University of the Basque Country (UPV/EHU)Vitoria-GasteizSpain
  2. 2.Biomedical Research Networking Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN)Vitoria-GasteizSpain

Personalised recommendations