Mechanism of Action of a Novel Advanced Wound Care Matrix

The authors recently described the safety and performance of a novel advanced wound care matrix (AWCM) in an IRB-approved retrospective study with 10 diabetic foot ulcer patients. This matrix consists of an upper compact layer and a lower porous layer, which mimic the structure of the basement membrane and dermis of human skin. Here we describe the investigation of possible mechanism of action underlying the clinical performance of this novel AWCM.

1) Incubation of the AWCM with specific matrix metalloproteinases (MMP) -1, -2, and -9, which are most abundant in chronic wound exudates, led to a reduction in the activity of MMP-1 by 55%, MMP-2 by 96%, and MMP-9 by 66%, suggesting an activity modulation by the AWCM.

2) Cell activity assays revealed an equally strong activity of healing-related growth factors (e.g., TGF-β1, bFGF, and VEGF) at 0 hours and 72 hours after incubation and after subsequent washing of the AWCM, indicating that these growth factors were bound and preserved by the AWCM.

3) Boyden Chamber Assays using human keratinocytes showed an equal number of migrated cells in wells incubated with the AWCM compared to growth supplement, which served as a positive control. Cell numbers in test and positive control were above the negative control. In addition, keratinocytes, fibroblasts, and endothelial cells were successfully grown on the AWCM. Thus, the AWCM provided a favorable environment that enabled cell attachment and migration.

Based on these data, we conclude that the novel bilayer AWCM supports the healing of diabetic foot ulcer by rebalancing MMPs and growth factors and by enabling cells to bind and migrate into the wound.