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The Diffusive Properties of Hydrogel Microcapsules for Cell Encapsulation

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Cell Microencapsulation

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1479))

Abstract

Hydrogel microcapsules have been used for decades to encapsulate cells and treat diseases ranging from neurodegenerative disorders to more systemic applications like Type I Diabetes. This cell encapsulation modality has been developed through more cumulative experiments than perhaps any other, owing to the relative ease of accessing the required materials, the commercial availability of droplet-generating instrumentation, and the mild microenvironment and unique permeability properties of hydrogels that are difficult to attain with alternative encapsulation systems employing thermoplastic materials. Because of their size and shape, microcapsules have an inherent advantage over macroencapsulation devices due to the more favorable surface area to volume ratio, which allows for greater efficiency in the amount of cellular cargo that is entrapped and enhanced nutrient exchange and efflux of secreted products. Unfortunately, with this significant positive benefit comes the caveat of difficult or impractical retrievability, highlighting the paradox that is particularly relevant as differentiated stem cell sources become more readily available. This chapter focuses on several techniques that can be used to evaluate the permeability and pore structure of hydrogel microcapsules, including a simplistic model for describing the diffusive behavior of alginate-polycation-alginate (APA) microcapsules with a liquid core, and an ancillary method to evaluate the ultrastructure of the APA membrane including morphometric analysis.

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References

  1. Chang T (1964) Semipermeable microcapsules. Science 146:524–525

    Article  CAS  Google Scholar 

  2. Elliott R, Tan P, Wilson R, Wolf L (2008) PRESS RELEASE: living cell technologies reports clinical benefit for all patients in diabetes trial. http://www.lct.com.au

  3. Martinsen A, Storro I, Skjak-Braek G (1992) Alginate as immobilization material: III. Diffusional properties. Biotechnol Bioeng 39(2):186–194

    Article  CAS  Google Scholar 

  4. Bouhadir KH, Alsberg E, Mooney DJ (2001) Hydrogels for combination delivery of antineoplastic agents. Biomaterials 22(19):2625–2633

    Article  CAS  Google Scholar 

  5. Lim F, Sun A (1980) Microencapsulated islets as bioartificial endocrine pancreas. Science 210(4472):908–910

    Article  CAS  Google Scholar 

  6. King A, Strand B, Rokstad A, Kulseng B, Andersson A, Skjak-Braek G, Sandler S (2003) Improvement of the biocompatibility of alginate/poly-L-lysine/alginate microcapsules by the use of epimerized alginate as a coating. J Biomed Mater Res A 64(3):533–539

    Article  Google Scholar 

  7. Liu X, Xue W, Liu Q, Yu W, Fu Y, Xiong X, Ma X, Yuan Q (2004) Swelling behaviour of alginate–chitosan microcapsules prepared by external gelation or internal gelation technology. Carbohydr Polym 56(4):459–464

    Article  CAS  Google Scholar 

  8. Altman JJ, Houlbert D, Chollier A, Leduc A, McMillan P, Galletti PM (1984) Encapsulated human islet transplants in diabetic rats. Trans Am Soc Artif Intern Organs 30:382–386

    CAS  Google Scholar 

  9. Thu B, Bruheim P, Espevik T, Smidsrod O, Soon-Shiong P, Skjak-Braek G (1996) Alginate polycation microcapsules. II. Some functional properties. Biomaterials 17(11):1069–1079

    Article  CAS  Google Scholar 

  10. Thanos C, Bintz B, Bell W, Qian H, Schneider P, MacArthur D, Emerich D (2006) Intraperitoneal stability of alginate-polyornithine microcapsules in rats: an FTIR and SEM analysis. Biomaterials 27(19):3570–3579

    CAS  Google Scholar 

  11. Veiseh O, Doloff J, Ma M, Vegas A, Tam H, Bader A, Li J, Langan E, Wyckoff J, Loo W, Jhunjhunwala S, Chiu A, Siebert S, Tang K, Hollister-Lock J, Aresta-Dasilva S, Bochenek M, Mendoza-Elias J, Wang Y, Qi M, Lavin D, Chen M, Dholakia N, Thakrar R, Lacik I, Weir G, Oberholzer J, Greiner D, Langer R, Anderson D (2015) Size- and shape-dependent foreign body immune response to materials implanted in rodents and hon-human primates. Nat Mater 14(6):643–651

    Article  CAS  Google Scholar 

  12. Kang J, Erdodi G, Kennedy J (2007) Third-generation amphiphilic conetworks. III. Permeabilities and mechanical properties. J Polym Sci A Polym Chem 45(18):4276–4283

    Article  CAS  Google Scholar 

  13. Schweicher J, Nyitray C, Desai TA (2014) Membranes to achieve immunoprotection of transplanted islets. Front Biosci (Landmark Ed) 19:49–76

    Article  CAS  Google Scholar 

  14. Lim F, Moss RD (1981) Microencapsulation of living cells and tissues. J Pharm Sci 70(4):351–354

    Article  CAS  Google Scholar 

  15. Leung YF, O’Shea GM, Goosen MF, Sun AM (1983) Microencapsulation of crystalline insulin or islets of Langerhans: an insulin diffusion study. Artif Organs 7(2):208–212

    Article  CAS  Google Scholar 

  16. Sakai S, Ono T, Ijima H, Kawakami K (2000) Control of molecular weight cut-off for immunoisolation by multilayering glycol chitosan-alginate polyion complex on alginate-based microcapsules. J Microencapsul 17(6):691–699

    Article  CAS  Google Scholar 

  17. Matsumoto T, Kawai M, Masuda T (1992) Influend of concentration and mannuronate/guluronate ratio on steady flow properties of alginate aqueous systems. Biorheology 29(4):411–417

    CAS  Google Scholar 

  18. van Schilfgaarde R, de Vos P (1999) Factors influencing the properties and performance of microcapsules for immunoprotection of pancreatic islets. J Mol Med 77(1):199–205

    Article  Google Scholar 

  19. Wang T, Lacik L, Brissova M, Anilkumar AV, Prokop A, Hunkeler D, Green R, Shahrokhi K, Powers AC (1997) An encapsulation system for the immunoisolation of pancreatic islets. Nat Biotechnol 15(4):358–362

    Article  CAS  Google Scholar 

  20. Addicks WJ, Flynn GL, Weiner N (1987) Validation of a flow-through diffusion cell for use in transdermal research. Pharm Res 4(4):337–341

    Article  CAS  Google Scholar 

  21. Pluen A, Netti P, Jain R, Berk D (1999) Diffusion of macromolecules in agarose gels: comparison of linear and globular configurations. Biophys J 77:542–552

    Article  CAS  Google Scholar 

  22. O’Leary TJ (1987) Concentration dependence of protein diffusion. Biophys J 52(1):137–139

    Article  Google Scholar 

  23. Nakagawa Y, Murai T, Hasegawa C, Hirata M, Tsuchiya T, Yagami T, Haishima Y (2003) Endotoxin contamination in would dressings made of natural biomaterials. J Biomed Mater Res 66B:347–355

    Article  CAS  Google Scholar 

  24. Kwok WY, Kiparissides C, Yuet P, Harris TJ, Goosen MFA (1991) Mathematical-modeling of protein diffusion in microcapsules - a comparison with experimental results. Can J Chem Eng 69(1):361–370

    Article  CAS  Google Scholar 

  25. Lee KY, Mooney DJ (2012) Alginate: properties and biomedical applications. Prog Polym Sci 37(1):106–126. doi:10.1016/j.progpolymsci.2011.06.003

    Article  CAS  Google Scholar 

  26. Tam SK, de Haan BJ, Faas MM, Halle J-P, Yahia LH, deVos P (2007) Adsorption of human immunoglobulin to implantable alginate-poly-L-lysine microcapsules: effect of microcapsule composition. J Biomed Mater Res A 89(3):609–615

    Google Scholar 

  27. Garfinkel MR, Harland RC, Opara EC (1998) Optimization of the microencapsulated islet for transplantation. J Surg Res 76:7–10

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Cytosolv, Inc., 117 Chapman St., Suite 107, Providence, RI, USA

    D. M. Lavin, B. E. Bintz & C. G. Thanos Ph.D.

  2. Brown University, Providence, RI, USA

    D. M. Lavin & B. E. Bintz

Authors
  1. D. M. Lavin
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  2. B. E. Bintz
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  3. C. G. Thanos Ph.D.
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Corresponding author

Correspondence to C. G. Thanos Ph.D. .

Editor information

Editors and Affiliations

  1. Wake Forest Institute for Regenerative Medicine Wake Forest School of Medicine, Winston-Salem, North Carolina, USA

    Emmanuel C. Opara

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Lavin, D.M., Bintz, B.E., Thanos, C.G. (2017). The Diffusive Properties of Hydrogel Microcapsules for Cell Encapsulation. In: Opara, E. (eds) Cell Microencapsulation. Methods in Molecular Biology, vol 1479. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6364-5_9

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  • DOI: https://doi.org/10.1007/978-1-4939-6364-5_9

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6362-1

  • Online ISBN: 978-1-4939-6364-5

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