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Strategies to reduce dendritic cell activation through functional biomaterial design ☆

Paper ID Volume ID Publish Year Pages File Format Full-Text
6940 525 2012 11 PDF Available
Title
Strategies to reduce dendritic cell activation through functional biomaterial design ☆
Abstract

Dendritic cells play a key role in determining adaptive immunity, and there is growing interest in characterizing and manipulating the interactions between dendritic cells and biomaterial surfaces. Contact with several common biomaterials can induce the maturation of immature dendritic cells, but substrates that reduce dendritic cell maturation are of particular interest within the field of cell-based therapeutics where the goal is to reduce the immune response to cell-laden material carriers. In this study, we use a materials-based strategy to functionalize poly(ethylene glycol) hydrogels with immobilized immunosuppressive factors (TGF-β1 and IL-10) to reduce the maturation of immature dendritic cells. TGF-β1 and IL-10 are commonly employed as soluble factors to program dendritic cells in vitro, and we demonstrate that these proteins retain bioactivity towards dendritic cells when immobilized on hydrogel surfaces. Following stimulation with lipopolysaccharide (LPS) and/or cytokines, a dendritic cell line interacting with the surfaces of immunosuppressive hydrogels expressed reduced markers of maturation, including IL-12 and MHCII. The bioactivity of these immunomodulatory hydrogels was further confirmed with primary bone marrow-derived dendritic cells (BMDCs) isolated from non-obese diabetic (NOD) mice, as quantified by a decrease in activation markers and a significantly reduced capacity to activate T cells. Furthermore, by introducing a second signal to promote BMDC-material interactions combined with the presentation of tolerizing signals, the multifunctional PEG hydrogels were found to further increase signaling towards BMDCs, as evidenced by greater reductions in maturation markers.

Keywords
Immunomodulation; Hydrogel; Surface modification; Adhesion molecule; Photopolymerization
First Page Preview
Strategies to reduce dendritic cell activation through functional biomaterial design ☆
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 14, May 2012, Pages 3615–3625
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering