Effects of Hyaluronic Acid Conjugation on Anti-TNF-alpha Inhibition of Inflammation in Burns

Biomaterials capable of neutralizing specific cytokines could form the basis for treating a broad range of conditions characterized by intense, local inflammation. Severe burns, spanning partial-to full-thickness of the dermis, can result in complications due to acute inflammation that contributes to burn progression, and early mediation may be a key factor in rescuing thermally injured tissue from secondary necrosis in order to improve healing outcomes. In this work we examined the effects on burn progression and influence on the inflammatory microenvironment of topical application of anti-TNF- alone, mixed with hyaluronic acid or conjugated to hyaluronic acid. We found that non-conjugated anti-TNF- decreased macrophage infiltration to a greater extent than that conjugated to hyaluronic acid; however there was little effect on the degree of progression or IL-1 levels. A simple transport model is proposed to analyze the results, which predicts qualitative and quantitative differences between untreated burn sites and those treated with the conjugates. Our results indicate that conjugation of anti-TNF- to high molecular weight hyaluronic acid provides sustained, local modulation of the post-injury inflammatory responses compared to direct administration of non-conjugated antibodies. Published in the Journal of Biomedical Materials Research A, v102 n5 p1527-1536, May 2014. Sponsored in part by NIH. Prepared in collaboration with the Department of Biomedical Engineering, the Department of Chemistry, and the McGowan Institute for Regenerative Medicine, Carnegie Mellon University, Pittsburgh, PA.