Device design and materials optimization of conformal coating for islets of Langerhans

Alice Tomei, Vita Manzoli, Christopher Fraker, Jaime Giraldo, Diana Velluto, Mejdi Najjar, Antonello Pileggi, Ruth Molano, Camillo Ricordi, Cherie L. Stabler, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Encapsulation of islets of Langerhans may represent a way to transplant islets in the absence of immunosuppression. Traditional methods for encapsulation lead to diffusional limitations imposed by the size of the capsules (600-1,000 μm in diameter), which results in core hypoxia and delayed insulin secretion in response to glucose. Moreover, the large volume of encapsulated cells does not allow implantation in sites that might be more favorable to islet cell engraftment. To address these issues, we have developed an encapsulation method that allows conformal coating of islets through microfluidics and minimizes capsule size and graft volume. In this method, capsule thickness, rather than capsule diameter, is constant and tightly defined by the microdevice geometry and the rheological properties of the immiscible fluids used for encapsulation within the microfluidic system. We have optimized the method both computationally and experimentally, and found that conformal coating allows for complete encapsulation of islets with a thin (a few tens of micrometers) continuous layer of hydrogel. Both in vitro and in vivo in syngeneic murine models of islet transplantation, the function of conformally coated islets was not compromised by encapsulation and was comparable to that of unencapsulated islets. We have further demonstrated that the structural support conferred by the coating materials protected islets from the loss of function experienced by uncoated islets during ex vivo culture.

Original languageEnglish
Pages (from-to)10514-10519
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number29
DOIs
StatePublished - Jul 22 2014

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Equipment Design
Islets of Langerhans
Capsules
Microfluidics
Transplants
Islets of Langerhans Transplantation
Hydrogel
Cell Size
Immunosuppression
Insulin
Glucose

Keywords

  • Alginate
  • Cell encapsulation
  • Cell transplantation
  • Polyethylene glycol

ASJC Scopus subject areas

  • General

Cite this

Device design and materials optimization of conformal coating for islets of Langerhans. / Tomei, Alice; Manzoli, Vita; Fraker, Christopher; Giraldo, Jaime; Velluto, Diana; Najjar, Mejdi; Pileggi, Antonello; Molano, Ruth; Ricordi, Camillo; Stabler, Cherie L.; Hubbell, Jeffrey A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 29, 22.07.2014, p. 10514-10519.

Research output: Contribution to journalArticle

Tomei, Alice ; Manzoli, Vita ; Fraker, Christopher ; Giraldo, Jaime ; Velluto, Diana ; Najjar, Mejdi ; Pileggi, Antonello ; Molano, Ruth ; Ricordi, Camillo ; Stabler, Cherie L. ; Hubbell, Jeffrey A. / Device design and materials optimization of conformal coating for islets of Langerhans. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 29. pp. 10514-10519.
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