Microfabricated microporous membranes reduce the host immune response and prolong the functional lifetime of a closed-loop insulin delivery implant in a type 1 diabetic rat model

verfasst von

Jason Li, Michael K.L. Chu, Claudia R. Gordijo, Azhar Z. Abbasi, Kuan Chen, Hibret A. Adissu, Matthias Löhn, Adria Giacca, Oliver Plettenburg, Xiao Yu Wu

Abstract

Implantation of a medical implant within the body inevitably triggers a host inflammatory response that negatively impacts its function and longevity. Nevertheless, the degree and severity of this response may be reduced by selecting appropriate materials, implant geometry, surface topography and surface treatment. Here we demonstrate a strategy to improve the biocompatibility of a chemically-driven closed-loop insulin delivery implant. A microfabricated microporous, poly(ethylene glycol)-grafted polydimethylsiloxane membrane was placed on top of the glucose-responsive insulin release plug of the implant. Implant biocompatibility was assessed in healthy rats while implant function was evaluated in a type 1 diabetic rat model. The microporous membrane with a small distance to the plug provided a geometric barrier to inflammatory cell migration and prevented leukocyte-mediated degradation of the plug for at least 30 days. Membrane-protected devices elicited a significantly milder inflammatory response and formation of a well-defined fibrous capsule at the device opening compared to unprotected devices. The device's glucose-responsiveness was nearly unchanged, although the insulin release rate decreased with decreasing pore size. The microporous membrane improved biocompatibility and prolonged invivo efficacy of the implant by ~3-fold. This work suggests the importance of implant design in modulating inflammatory response and thereby extending the functional duration of the implant.

Externe Organisation(en)

University of Toronto
Sanofi-Aventis Deutschland GmbH

Typ

Artikel

Journal

BIOMATERIALS

Band

47

Seiten

51-61

Anzahl der Seiten

11

ISSN

0142-9612

Publikationsdatum

04.2015

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Biophysik, Bioengineering, Keramische und Verbundwerkstoffe, Biomaterialien, Werkstoffmechanik

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1016/j.biomaterials.2015.01.005 (Zugang: Geschlossen)