4.8 Article

PEG-based hydrogels as an in vitro encapsulation platform for testing controlled beta-cell microenvironments

Journal

ACTA BIOMATERIALIA
Volume 2, Issue 1, Pages 1-8

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2005.10.005

Keywords

islet encapsulation; poly(ethylene glycol) hydrogels; beta-cell viability

Funding

  1. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK076084, P30DK057516] Funding Source: NIH RePORTER
  2. NIDDK NIH HHS [DK057516, R01 DK076084-01A2, R01 DK076084] Funding Source: Medline

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An in vitro encapsulation platform for systematically testing the effects of microenvironmental parameters on encapsulated islets was developed. The base encapsulation matrix was a biocompatible hydrogel formed via the photoinitiated polymerization of dimethacrylated poly(ethylene glycol) (PEGDM). The resulting inert encapsulation matrix affords control over the biochemical and biophysical cellular microenvironment and the introduction of systematic changes to this environment. The compatibility of the PEG-based encapsulation platform with pancreatic beta-cells was first established using a murine beta-cell line, MIN6. When cell-cell contacts were introduced via aggregation of MIN6 beta-cells prior to encapsulation, MIN6 beta-cells remained viable within the PEG hydrogel platform throughout 3 weeks of in vitro culture. Proliferating cells were observed within encapsulated MIN6 aggregates qualitatively with bromodeoxyuridine staining and quantitatively by measuring the DNA content of encapsulation samples with time. MIN6 beta-cells were encapsulated in hydrogels formed from three PEGDM macromers of varying molecular weights ((M) over bar (n), = 4000, 8000, 10,000 g/mol), and the resulting differences in hydrogel crosslinking density, which influences transport properties, did not affect encapsulated beta-cell survival. Encapsulated MIN6 beta-cells transplanted into diabetic mice returned blood glucose levels to normal levels, indicating in vivo function. Finally, the compatibility of the PEG encapsulation system with freshly isolated islets was confirmed. (c) 2005 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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