Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10514-9. doi: 10.1073/pnas.1402216111. Epub 2014 Jun 30.

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

Author information

1
Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136; atomei@med.miami.edu.
2
Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy;
3
Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;
4
Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;Department of Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL 33146 and.
5
Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
6
Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.

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.

KEYWORDS:

alginate; cell encapsulation; cell transplantation; polyethylene glycol

PMID:
24982192
PMCID:
PMC4115512
DOI:
10.1073/pnas.1402216111
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center