Controlled Release of Dexamethasone from Organosilicone Constructs for Local Modulation of Inflammation in Islet Transplantation

Jessica D. Weaver, Yun Song, Ethan Y. Yang, Camillo Ricordi, Antonello Pileggi, Peter Buchwald, Cherie L. Stabler

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Inflammation is a significant detriment to the engraftment of cells and tissues, particularly for islet transplantation, where a low tolerance for the inflammatory milieu results in significant graft loss. Local treatment with anti-inflammatories, such as glucocorticoids, provides the benefits of site-targeted delivery with minimization of the broad side effects associated with systemic delivery. Polydimethylsiloxane (PDMS) is a flexible platform that is capable of providing sustained delivery of hydrophobic drugs. Here, we evaluated the capacity of PDMS constructs loaded with the anti-inflammatory glucocorticoid dexamethasone (Dex) to locally mitigate inflammation in islet grafts. Dex-PDMS constructs, fabricated in rod or disk geometries, demonstrated prolonged and sustained release at therapeutically relevant levels. In vitro, Dex-PDMS constructs inhibited endotoxin-induced human monocyte and macrophage activation, but they did not impair islet viability or function. Dex-PDMS rods, co-transplanted with islet-seeded scaffolds in a murine model, demonstrated suppression of host inflammatory responses during early- and late-phase engraftment, without significantly altering islet graft potency. The facile nature of these glucocorticoid-doped PDMS constructs allows for the optimization of targeted dose delivery with wide applicability in cell and tissue transplantation.

Original languageEnglish (US)
Pages (from-to)2250-2261
Number of pages12
JournalTissue Engineering - Part A
Volume21
Issue number15-16
DOIs
StatePublished - Aug 1 2015

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ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials

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