The inhibition of matrix metalloproteinase activity in chronic wounds by a polyacrylate superabsorber.
Excessive matrix metalloproteinase (MMP) levels have been observed in wound fluid of impaired healing wounds. This is thought to interfere with granulation tissue formation as newly formed extracellular matrix and cytokines are degraded and the wound becomes deadlocked, unable to progress to the next healing stages. In the cleansing phase, associated with high MMP activity levels, hydroactive wound dressings containing polyacrylate superabsorber particles are particularly effective. We tested whether these particles can block MMP activity in wound fluid obtained from chronic venous leg ulcers. Polyacrylate superabsorber particles inhibited MMP activity by more than 87% in a fluorogenic peptide substrate assay. Further analysis revealed two underlying molecular mechanisms. First, experiments showed direct binding of MMPs to the particles. Secondly, polyacrylate superabsorber particles can bind Ca2+ and Zn2+ ions competing with MMPs for divalent ions required for enzymatic activity. Furthermore, we provide the first evidence in vivo that MMPs bind effectively to polyacrylate superabsorber particles within the hostile environment of chronic wounds. We conclude that polyacrylate superabsorber particles can rescue the highly proteolytic microenvironment of non-healing wounds from MMP activity so that more conductive conditions allow healing to proceed.
Eming
Sabine
S
Department of Dermatology, University of Cologne, Kerpener Strasse 62, 50924 Cologne, Germany.
Smola
Hans
H
Hartmann
Berenike
B
Malchau
Gebhart
G
Wegner
Ronny
R
Krieg
Thomas
T
Smola-Hess
Sigrun
S
D000180:Acrylic Resins / Q000494:pharmacology*; D002908:Chronic Disease; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology*; D014947:Wounds and Injuries / Q000201:enzymology*
D000180:Acrylic Resins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; C006903:carbopol 940