期刊
ACTA BIOMATERIALIA
卷 6, 期 12, 页码 4708-4715出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2010.06.029
关键词
Antibody; Biomimetic material; Pro-inflammatory cytokines; Hyaluronic acid; Inflammation
资金
- U.S. Army DAMD [17-02-1-0717]
- Armed Forces Institute for Regenerative Medicine [W81 x WH-08-2-0032]
- NIH [1R43GM085897]
- 3 M Non-Tenured Faculty
- The Sanford C. Bernstein and Company, LLC [P01 CA 101,944-01A2]
- The Clinical and Translational Research Program (Reis, Steven) [1U54RR023506-01]
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-1 beta and tumor necrosis factor-alpha 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. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据