Journal
WOUND REPAIR AND REGENERATION
Volume 18, Issue 3, Pages 302-310Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1524-475X.2010.00591.x
Keywords
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Funding
- U.S. Army [DAMD 17-02-1-0717]
- Department of Defense [W81XWH-08-2-0032]
- 3M Non-Tenured Faculty Grant
- Sanford C. Bernstein and Company [1 P01 CA 101944-01A2]
- Clinical and Translational Research Program [1U54RR023506-01]
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Wound healing represents a highly regulated, orchestrated response of cells recruited to sites of injury. High molecular weight hyaluronic acid was conjugated with monoclonal antibodies to the cytokine interleukin-1 beta to create a matrix-forming polymer capable of modifying healing. Using gel electrophoresis and fluorescence immunosorbent assays, we determined a degree of antibody functionalization per hyaluronic acid chain of 13.6 +/- 1.6%. The biological activity of the conjugate in vitro, measured using a nuclear factor-kappa B translocation assay in activated THP-1 monocytes, was comparable in inhibiting cytokine signaling to a similar level as the unconjugated antibody. Incisional wound studies in Sprague-Dawley rats indicates that viscous hyaluronic acid solutions were immunologically active, but covalent functionalization with antibodies against tumor necrosis factor-alpha and interleukin-1 beta resulted in significant reductions in the inflammatory response. Covalent attachment of cytokine-neutralizing antibodies to matrix-forming polymers could lead to the development of materials capable of locally regulating wound healing and inflammatory responses in the setting of tissue regeneration.
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