Protease Modulating Properties of Multi-Action Wound Treatment

Introduction: The aim of this study was to assess the capability of a novel Multi-Action Treatment (MAT*) dressing to modulate levels of Matrix Metalloproteinase (MMP-2 and MMP-9) and Neutrophil Elastase (ELA2). MAT dressing comprises a formulation including povidone iodine incorporated into a carboxymethyl cellulose (CMC) gelling fibre substrate.

Method: Samples of MAT, CMC substrate without the agent and positive control dressing (1cm x 1cm) were placed in 24-well plates in triplicate and activated with deionised water. One millilitre of prepared protease solution, was added to each dressing sample and to “No dressing” control wells. Plates were sealed and incubated at 37 ± 2°C and 50 ± 5 rpm. Supernatants were collected after 1 hour, 4 hours and 24 hours incubation. The concentration of protease remaining in each supernatant was determined using the appropriate ELISA method.

Results: Following incubation with MAT no MMP-2 or MMP-9 was detected in samples at all timepoints tested and no ELA2 was detected at or after 4 hours. All controls performed as expected. No dressing control slightly reduced MMP levels and with stable levels of elastase. Positive control, reduced MMP-2 to zero at 24 hours, reduced MMP-9 to zero at all timepoints and reduced ELA2 but not to zero. The CMC dressing performed similarly to the no dressing control against MMP-2. When tested against MMP-9 and ELA2 the CMC dressing reduced the amount of protease present over time but did not reduce it to below detection limits.

Discussion: No MMP-2, MMP-9 and ELA2 were detected in samples following incubation with the MAT dressing. The increased levels of proteinases detected in wound exudate have been correlated to poor wound healing, most likely due to the excessive degradation of key extracellular matrix components essential for tissue repair and the inhibition of reepithelialisation. Wound dressings like MAT which reduce MMP levels in a wound and may improve wound healing.In other studies (1, 2) MAT has been shown to disrupt biofilm and to be bactericidal. The design intent is to combine these actions with the protease modulation in a single treatment.