|Diegelmann, Robert - VCU MEDICAL CENTER|
Submitted to: Cellulose
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 1, 2009
Publication Date: May 24, 2009
Citation: Edwards, J.V., Howley, P.S., Prevost, N.T., Condon, B.D., Arnold, J.W., Diegelmann, R. 2009. Positively and Negatively Charged Ionic Modifications to Cellulose Assessed as Cotton-Based Protease-Lowering and Haemostatic Wound Agents. Cellulose. 16(5):911-921. Interpretive Summary: Chronic wounds are a major worldwide health problem. This research is directed at strengthening the role of cotton-based textiles in the growing market of high tech wound dressings. This paper demonstrates an important technology for development of value-added cotton-based wound dressings. An improvement on cotton gauze to accelerate healing in patients with bedsores and ulcers and promote hemostasis of bleeding wounds is the ultimate goal of this work. The paper shows how cotton gauze can be modified ionoically to reduce the activity of a destructive enzyme found to keep chronic wounds from healing, and to promote gelling and clotting of blood. The destructive proteases found in chronic wound are human neutrophil elastase and collagenase. High levels of elastase collagenase in the non-healing wound break down the recruitment of new tissue necessary for healing to take place. The advantage of this work suggests that a novel gauze prepared from positively and negatively modified cellulose may in the future be preferable over standard gauze widely used in hospitals and nursing homes at present. This preference is based on the rational design approach which soaks up elastase activity and decreases the high levels of activity found to be destructive in the non-healing wound. In addition the positively charged character of chitosan-grafted cotton promotes gelling of blood on the fabric and reduces blood flow and wicking into the fabric. The addition of ionically derivatized cotton to the wound dressing market would boost cottons share in the rapidly growing field of high tech wound care, and aid both the consumer and the cotton farmer by providing an economic value-added product.
Technical Abstract: Recent developments in cellulose wound dressings targeted to different stages of wound healing have been based on structural and charge modifications that function to modulate events in the complex inflammatory and hemostatic phases of wound healing. Hemostasis and inflammation comprise two overlapping but distinct phases of wound healing wherein different dressing material properties are required to bring pathological events under control when they present as a result of trauma or chronic wounds. Thus, we have designed cellulose wound dressings with properties that function through modified fiber surface properties to lower protease levels in the chronic wound, and promote clotting in hemorrhaging wounds. With this in mind three finishing chemistries utilizing traditional pad-dry-cure approaches were explored for their potential to confer charged properties to cotton dressings. Cellulose dressings designed to remove cationic serine proteases from highly exudative chronic wounds were created to present negatively charged fibers as an ion exchange mechanism of protease-lowering. Phosphorylated cotton and polycarboxylic acid crosslinked cotton were prepared to examine their ability to remove human neutrophil elastase (HNE) from surrogate wound fluid. A cellulose phosphorylation reaction utilizing sodium hexametaphosphate:urea was explored to optimize cellulose phosphorylation as a function of HNE sequestration efficacy. Acid catatlyzed crosslinking of cellulose with butane-tetracarboxylic acid also resulted in a negatively charged dressing that removed HNE from solution more effectively than phosphorylated cellulose. Collagenase sequestration was also assessed with phosphorylated cellulose and polycarboxylic acid crosslinked cellulose derivatives. Butanetetracarboxylic acid and phosphorylated cellulose functioned to remove collagenase from solution most effectively. Cellulose dressings designed to accelerate thrombosis and aggregation of blood platelets were prepared with a view to examining derivatized cotton fibers bearing a net positive charge to promote hemostasis. Cellulose and chitosan dressings bearing an aminoglucan functionality were created by grafting chitosan on cotton and preparing aminized cotton. The preparation of chitosan-grafted cotton dressings was completed with a citric acid grafting onto cellulose. Aminized cotton was functionalized as an ethylamino-ether cellulose derivative. The chitosan-grafted and aminized cotton demonstrated a dose response gelling of citrated sheep blood.