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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

Paper ID Volume ID Publish Year Pages File Format Full-Text
5729 423 2015 11 PDF Available
Title
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
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 in vivo 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.

Keywords
Biocompatibility; Diabetes; Closed-loop insulin delivery implant; Microfabrication; Microporous membrane; Drug delivery implant
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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
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 47, April 2015, Pages 51–61
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us