title: A nanoporous, transparent microcontainer for encapsulated islet therapy.
abstract: Present-day islet encapsulation techniques such as polymer microcapsules and microelectromechanical system (MEMS)-based biocapsules have shown promise in insulin replacement therapy, but they each have limitations-the permeability characteristics of existing polymeric capsules cannot be strictly controlled because of tortuosity and the large size of present-day MEMS biocapsules leads to necrotic regions within the encapsulation volume. We report on a new microcontainer to encapsulate and immunoprotect islets/beta cells that may be used for allo- or xenotransplantation in cell-based therapy. The microcontainers have membranes containing nanoslots to permit the bidirectional transport of nutrients, secretagogues, and cellular products while immunoprotecting the encapsulated cells. The 300-microm microcontainers were fabricated from an epoxy-based polymer, SU-8, with 50-microm-thick walls. Arrays of 25-nm wide slots were created in the SU-8 microcontainer lid. Isolated mouse islets were encapsulated in the microcontainer, and their physiological response to glucose was studied with fluorescence and two-photon imaging over 48 hours. The physiological response of the encapsulated islets was indistinguishable from controls. An agarose-filled microcontainer was imaged with magnetic resonance imaging to demonstrate the feasibility of future noninvasive, in vivo imaging. The SU-8 microcontainers maintained mechanical integrity upon islet loading and mechanical manipulation. Islet encapsulation, as well as the ability to visualize islet function within these transparent microcontainers, was demonstrated.
authors.affiliation: The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Barjor
authors.initials: B
authors.lastname: Gimi
authors.forename: Joonbum
authors.initials: J
authors.lastname: Kwon
authors.forename: Andrey
authors.initials: A
authors.lastname: Kuznetsov
authors.forename: Behroze
authors.initials: B
authors.lastname: Vachha
authors.forename: Richard L
authors.initials: RL
authors.lastname: Magin
authors.forename: Louis H
authors.initials: LH
authors.lastname: Philipson
authors.forename: Jeong-Bong
authors.initials: JB
authors.lastname: Lee
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D016381:Islets of Langerhans Transplantation / Q000295:instrumentation* / Q000379:methods*; D008567:Membranes, Artificial; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures; D014183:Transplantation, Heterologous
chemical_list: D001786:Blood Glucose; D008567:Membranes, Artificial