In 2010, it was estimated that 6.5 million people in the United States alone suffered from chronic wounds, accruing an annual cost of about $2.5 billion. Furthermore, experts predict that the burden of chronic wounds will increase rapidly in the near future due to increasing medical costs, an aging population, and the emergence of antibiotic resistant bacteria. A chronic wound is considered a wound that does not heal in an orderly set of stages or within a time period of about three months. The etiology of chronic wounds is very diverse. One of the most prevalent reasons patients have persistent chronic wounds is that their bodies produce too many proteases at the wound site. In turn, these proteases degrade the extracellular matrix of the wound site which acts as a scaffold for new cells to migrate and grow. Proteases have also been shown to decrease healing rates by degrading growth factors that are needed for recruiting wound healing cells and inducing cellular proliferation. Wound healing progresses through three successive stages known as inflammation, proliferation, and remodeling. Ultimately, the degradation of the extracellular matrix and growth factor cause the wound to remain stuck in the inflammation phase, thus unable to heal.

We will use synthetic biology principles to help treat chronic wounds by targeting the overproduction of wound site protease.

• For Aim 1 we will genetically engineer E. coli to produce a protease inhibitor and platelet derived growth factor.
• For Aim 2 we will purify the protease inhibitor and platelet derived growth factor in a bioreactor.
• For Aim 3 we will design a collagen bandage that mimics the human extracellular matrix, and infuse it with purified protease inhibitor and platelet derived growth factor.

Our approach is two-fold. By infusing the collagen extracellular matrix with platelet derived growth factor and protease inhibitor, chronic wounds should be able to progress past the inflammation phase and begin healing once again.