title: Device design and materials optimization of conformal coating for islets of Langerhans.
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.
authors: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136; atomei@med.miami.edu.
authors: Alice A
authors: http://orcid.org/0000-0002-5059-6303
authors: AA
authors: Tomei
authors: 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;
authors: Vita
authors: V
authors: Manzoli
authors: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;
authors: Christopher A
authors: CA
authors: Fraker
authors: 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.
authors: Jaime
authors: J
authors: Giraldo
authors: Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors: Diana
authors: D
authors: Velluto
authors: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;
authors: Mejdi
authors: M
authors: Najjar
authors: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;
authors: Antonello
authors: http://orcid.org/0000-0001-7819-2813
authors: A
authors: Pileggi
authors: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;
authors: R Damaris
authors: RD
authors: Molano
authors: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;
authors: Camillo
authors: C
authors: Ricordi
authors: 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.
authors: Cherie L
authors: CL
authors: Stabler
authors: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors: Jeffrey A
authors: JA
authors: Hubbell
mesh_terms: D000464:Alginates / Q000494:pharmacology; D000818:Animals; D002449:Cell Aggregation; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003198:Computer Simulation; D004867:Equipment Design; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D057446:Hydrodynamics; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D044085:Microfluidics / Q000295:instrumentation*; D008863:Microspheres; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000494:pharmacology; D015203:Reproducibility of Results
chemical_list: D000464:Alginates; D020099:Coated Materials, Biocompatible; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D020723:Glucuronic Acid
keywords: alginate; cell encapsulation; cell transplantation; polyethylene glycol