The Direct Inhibition of MMP–2 and MMP–9 by an Enzyme Alginogel: A Possible Mechanism of Healing Support for Venous Leg Ulcers

Flaminal Forte is an enzyme alginogel,whose activity depends on the absorption and binding of matrix metalloproteinases (MMPs), which are known to play a crucial role in delayed wound healing. The aim of the study was to evaluate the influence of Flaminal on MMP-2/-9 activity in ulcer exudate, ex vivo. Eight patients with bilateral venous leg ulcers were treated for 4 weeks with Flaminal Forte covered by hydrocolloid ('F' wounds), or with hydrocolloid alone ('H' wounds) as a reference control. Clinical assessment did not reveal any differences between F and H wounds regarding surface reduction and general wound condition. Nevertheless, although non-significant, there was a visible difference in peri-wound skin appearance in F wounds, as compared to H wounds. The wound exudate contained high MMP-2/-9 levels, which gradually decreased as wounds healed. The attenuation of MMPs was stronger in F than in H exudate, however, in standard zymography this difference appeared non-significant. Realtime zymography revealed that Flaminal mediated a powerful direct inhibition of gelatinolytic activity of wound exudate and of recombinant MMP-2/-9 in vitro.