In vitro binding of matrix metalloproteinase-2 (MMP-2), MMP-9, and bacterial collagenase on collagenous wound dressings.

Chronic wounds are characterized by failure in wound-healing response and a delay in healing or nonclosure of the wounds. This results in a high effort in clinical treatment and/or home care. A major difference between acute wounds and chronic wounds is the imbalance of proteinase inhibitors and proteinase activity that regulates the degradation and regeneration of the extracellular matrix proteins. Collagen and collagen/oxidized regenerated cellulose dressings act as a competitive substrate for matrix metalloproteinase-2, matrix metalloproteinase-9, and bacterial collagenase and influence this imbalance positively. Both wound dressings, approved for chronic wound treatment, the bovine collagen type I sponge and the oxidized regenerated cellulose collagen sponge, did not differ significantly in their sorption profiles for all enzymes. In general, binding was enhanced with a longer incubation time. The density of the device and the accessible surface, which can be controlled by the manufacturing process, are the crucial factors for the efficiency of the wound dressing.

A model describing the effect of enzymatic degradation on drug release from collagen minirods.

A drug delivery system, named minirod, containing insoluble non-cross-linked collagen was prepared to investigate the release of model drug compounds. To characterise the complete drug release process properly, a mathematical model was developed. Previously, a mathematical model describing water penetration, matrix swelling and drug release by diffusion from dense collagen matrices has been introduced and tested. However, enzymatic matrix degradation influences the drug release as well. Based on experimental data, a model was developed which describes drug release by collagenolytic matrix degradation based on enzyme diffusion, adsorption and cleavage. Data for swelling, collagen degradation and FITC dextran release from insoluble equine collagen type I minirods were collected. Sorption studies demonstrated a tight sorption of collagenase on collagen surfaces that follows a Freundlich sorption isotherm and results in a degradation constant of 3.8x10(-5) mol/l for the minirods. The diffusion coefficients of FITC dextran 20 and 70 (3x10(-3) and 2.4x10(-3) cm2/h) in water were analyzed by fluorescence correlation spectroscopy (FCS). Using these data, the mathematical model was verified by two-dimensional simulations. The numerical results agreed well with the measurements.