Expression of matrix-metalloproteases in the fluid of chronic diabetic foot wounds treated with a protease absorbent dressing

Abstract

It is well known, that wound healing in diabetes is impaired. Persistently high levels of matrix-metalloproteases (MMPs) contribute to wound persistence. The topical use of protease-inhibitors might beneficially affect wound healing.

Research design and methods: 19 patients with chronic diabetic foot lesions (Wagner/Armstrong 2A) were studied. 6 patients received "good standard wound care", 13 patients were treated with a protease-inhibitor-modulating-matrix (ORC/collagen matrix) that was changed daily. At day 1 and 5 biopsies were taken from the wounds; wound fluids were collected daily. Biopsies were analysed using quantitative real-time-PCR and all samples were analysed using ELISA and zymography for MMPs, TIMPs, IL 1-β and TNFα levels.

Results: No differences in mRNA-expression of MMPs, TNFα and for MMP levels in wound tissue were detected between both groups or between the 2 sampling time points. MMP-2 active was significantly reduced in wound fluids of ORC/collagen treated lesions (p=0.043) after 5 days. MMP-2 pro was also reduced by about 25% when compared to increasing levels in the control group (+27%). We observed a significant reduction of the wound area in the ORC/collagen group (p=0.003).

Conclusions: Local treatment with a protease-inhibitor has a beneficial effect on wound healing. In contrast to unchanged mRNA-levels and protein levels of MMPs there was a clear reduction of MMP-2-levels in wound fluids. Our data support the potential role of ORC/collagen as a wound dressing. Modulation of MMPs appears to be beneficial in the treatment of chronic diabetic wounds.