Protease Indicator for Chronic Wound Management

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DESCRIPTION (provided by applicant): Chronic wounds are characterized by an overabundant presence of polymorphonuclear leukocytes(PMN's) which produce excessive elastase and the PMN collagenase , MMP-8. Collagenase destroys the wound matrix while elastase degrades growth factors and their receptor sites. These excessive proteases can be lowered by radical surgical debridement of the wound to promote healing. Once the wound proteases are lowered, host growth factors will be functional and/or the clinician can add extrinsic growth factors to the wound without degradation by these deleterious enzymes. More recently, protease sequestering dressings have been developed to lower protease content for improved healing. However, determination that the protease level has been lowered requires laboratory study of wound fluids or biopsies with at least a 24 hour delay before the information is returned to the clinician. Using the methodology to be developed in this proposal, a rapid, safe, inexpensive bed-side measurement of collagenase and elastase can be made which will determine when the protease sequestering dressing can be stopped safely. At present, the decision to change to another form of dressing is made imperically by simply observing the appearance of the wound. 2 approaches will be evaluated. The first approach will be to assay both proteases using rapid immunochromatographic methods. The second approach will be to assay elastase by a rapid colorimetric or fluorometric method. The methods will be validated using purified proteins, artificial wound fluids, and patient wound fluid samples. The assays used to develop this product are standard and should lead to a commercial product development in a Phase II study. Commercial production of the device and FDA approval as such should be straight forward. Cost of production will be low and therefore, broad usage and company profit is expected. The benefits to our patient population with chronic wounds should be significant.