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

摘要

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.