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Design principles for cytokine-neutralizing gels: Cross-linking effects

Paper ID Volume ID Publish Year Pages File Format Full-Text
2016 97 2010 8 PDF Available
Title
Design principles for cytokine-neutralizing gels: Cross-linking effects
Abstract

Constructs composed of cytokine-neutralizing antibodies conjugated to high-molecular-weight hyaluronic acid have been shown to be effective at controlling inflammatory responses in vivo. A critical question in the development of this new class of biomaterial is whether crosslinked conjugates have similar anti-inflammatory effects, which would open up a broad range of tissue engineering applications in which the material would have intrinsic inflammation-controlling function. To test this, high-molecular-weight hyaluronic acid was conjugated with monoclonal antibodies to the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in two forms of the material: viscous, non-crosslinked polymer–antibody conjugates and crosslinked, elastomeric polymer–antibody conjugates. The cytokine affinities of both constructs were validated using molecular characterization methods, and the biological activities were tested through subcutaneous implantation in Sprague–Dawley rats. In vitro, both forms of these constructs are capable of binding cytokines, but in vivo only the non-crosslinked polymer significantly reduces markers of acute inflammation compared to controls that lack the antibodies. We propose that these materials function by retarding cytokine diffusion, with the non-crosslinked polymers being capable of retarding the diffusion of cytokines in the extracellular matrix and preventing engagement with receptors. In contrast, crosslinked materials have long diffusion lengths into the gel compared with those between cells on the surface of the material, which may make them ineffective at sequestering pro-inflammatory cytokines on biologically relevant timescales. These results suggest an important design principle for preparing cytokine-regulating materials based on consideration of transport phenomena.

Keywords
Antibody; Biomimetic material; Pro-inflammatory cytokines; Hyaluronic acid; Inflammation
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Design principles for cytokine-neutralizing gels: Cross-linking effects
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 6, Issue 12, December 2010, Pages 4708–4715
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