Submitted to: Biomedical Materials Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/6/2006
Publication Date: 5/3/2007
Citation: Edwards, J.V., Howley, P.S., Condon, B.D. 2007. Human Neutrophil Elastase and Collagenase Sequestration with Phosphorylated Cotton Wound Dressings. Journal of Biomedical Materials Research Part A. 83A(2):446-454. Interpretive Summary: This manuscript addresses a major worldwide health care problem involving the treatment of chronic wounds with new wound dressings designed to lower destructive levels of proteases found in non-healing wounds. The research reported in this paper demonstrates how two different types of cotton phosphorylation reactions can be used to create a simple and potent protease-lowering wound dressing. These results have important implications in the potential commercialization of a cotton—based chronic wound dressing. The paper shows how the phosphorylated cotton gauze is designed and tested to demonstrate the uptake of two key destructive proteases found in the chronic wound. The use of this type of cotton gauze in chronic wound patients may occur in the future since clinical trials and commercialization is currently occurring with this type of dressing. It also provides a value added cotton product that meets and unmet consumer need, and provides a route for better cotton utilization to further assist the cotton farmer.
Technical Abstract: The design and preparation of wound dressings that redress the proteolytic imbalance in chronic wounds has become an important goal of wound healing and medical materials science. Recent studies have demonstrated that chronic wounds contain high levels of tissue and cytokine destroying proteases including matrix metalloprotease and neutrophil elastase. Thus, the lowering of excessive protease levels in the wound environment prevents the breakdown of extracellular matrix proteins and growth factors necesssary for wound healing. A form of phosphorylated cotton gauze was prepared to target sequestration of proteases from chronic wound exudate through a cationic uptake binding mechanism involving salt bridge formation of the positively charged amino acid side chains of the protease with the phosphate counterions of the wound dressing fiber. Two types of phosphorylated cotton gauze were prepared from sodium hexametaphosphate and diammonium phosphate in separate formulations and applied to cotton gauze by pad/dry/cure methods. The phosphorylated cotton gauze samples were assessed for their ability to lower elastase and collagenase activity. Sodium hexametaphosphate and diammonium phosphate-treated cotton lowered elastase activity 40-70% more effectively than untreated cotton gauze under conditions that mimic chronic wound exudate. The efficacy of the phosphorylated cotton was directly related to the pH of the surface of the dressing. The capacity of the modified gauze to sequester continued elastase secretions similar to that found in a chronic wound over a twenty-four hour period was retained within a 20 percent loss of capacity and was dose dependent with a total of 20 mUnits of elastase removed.