Immune stimulating responses of biopolymers with particular reference to treatment of chronic wounds

Chronic wounds are a major world health problem; estimated to affect 3% of the population over the age of 65. There is a demand in the wound healing marked for new efficient products. The chronic wound bed represents a very complex system where bacteria a nd their products and degraded proteins constitute important elements. In order for the wound to heal, it is essential to switch the balance in the wound bed towards a normal inflammatory process with the production of proinflammatory cytokines. Biopolyme rs, including alginates, are widely used in dressings for chronic, non-healing skin wounds, however, their mechanisms of actions have so far largely been unknown. We hypothesize that certain alginate structures may stimulate healing of chronic wounds by i nducing a local pro-inflammatory reaction with the production of cytokines and chemokines. Alginates are linear copolymers of ?-D-mannuronic acid (M) and its C5-epimer ?-L-guluronic acid (G). Previous work by the partners in this project has shown that t he ratio and distribution of G-residues affects the immunostimulating properties of alginates. The main goal in this project is to develop a non-toxic immune stimulating alginate for treatment of chronic wounds. A wide range of different alginate substra tes will be produced by fermentation of genetically engineered bacterial strains. The alginates, or oligomers thereof, will subsequently be characterized for their ability to regulate expression of genes that control inflammation and tissue repair. A huma n acute wound model will be established for examining the effects of different alginates on wound closure in the presence and absence of bacteria isolated from chronic wounds. Based on the data generated from the cell based assays, expression studies and the work with the acute wound model, we will design a production strain/process for in vivo production of alginate substrates with optimal biological effect for treatment of chronic wounds.