The effects of cell-matrix interactions on encapsulated beta-cell function within hydrogels functionalized with matrix-derived adhesive peptides.

Abstract

The influence of matrix-derived adhesive peptide sequences on encapsulated beta-cell survival and glucose-stimulated insulin release was explored by covalently incorporating synthetic peptide sequences within a model encapsulation environment. Photopolymerized poly(ethylene glycol) (PEG) hydrogels were functionalized via the addition of acrylate-PEG-peptide conjugates to the polymer precursor solution prior to beta-cell photoencapsulation. Individual MIN6 beta-cells were encapsulated in the presence of the laminin-derived recognition sequences, IKLLI, IKVAV, LRE, PDSGR, RGD, and YIGSR, and the collagen type I sequence, DGEA. In the absence of cell-cell and cell-matrix contacts, encapsulated MIN6 beta-cell survival diminishes within one week; however, in PEG hydrogel derivatives including the laminin sequences IKLLI and IKVAV, encapsulated beta-cells exhibit preserved viability, reduced apoptosis, and increased insulin secretion. Interactions with the laminin sequences LRE, PDSGR, RGD, and YIGSR contribute to improved viability, but insulin release from these samples was not statistically greater than that from controls. MIN6 beta-cells were also encapsulated with various concentrations of IKLLI and IKVAV (0.05-5.0mm), individually, and the peptide combinations IKLLI-IKVAV, IKVAV-YIGSR, and PDSGR-YIGSR to explore synergistic effects. The presented results give evidence that synthetic peptide epitopes may be useful in the design of an islet encapsulation environment that promotes cell survival and function via targeted cell-matrix interactions.