The Effects of a Broad-Spectrum Matrix Metalloproteinase Inhibitor on Characteristics of Wound Healing

Abstract

This study investigates the effects of a broad-spectrum matrix metalloproteinase inhibitor (MMP-i) on the rate of closure, hydroxyproline deposition, and macrophage infiltration in healing wounds. Full-thickness excisional wounds were created on the dorsal surface of hairless mice. Two experimental groups were used to measure rates of wound closure: (a) MMP-i administration (0.03, 0.3, 3.0, and 30 w g/mL) on days 0-1 postwounding (inflammatory phase) and (b) MMP-i administration (0.03, 0.3, 3.0, and 30 w g/mL) on days 6-8 postwounding (proliferative phase). Additionally, hydroxyproline deposition and percent macrophage infiltration were measured in skin wound margins on days 2, 8, and 16 postwounding. MMP-i administration at concentrations of 0.03, 0.3, and 3.0 w g/mL on days 0-1 postwounding significantly ( p < .05) increased the rate of wound closure. No significant effect on the rate of wound closure was observed with MMP-i administration on days 6-8 postwounding. Hydroxyproline deposition was significantly ( p < .05) increased on day 8 postwounding, and the percent macrophage infiltration was significantly ( p < .05) decreased on day 2 postwounding by MMP-i administration on days 0-1 postwounding. These experiments demonstrate that MMP-i administration during the inflammatory phase significantly affects several characteristics of wound healing. We postulate that these effects may be attributed to decreased degradation of ECM components, increased concentrations of endogenous growth factors, and a shortened inflammatory phase.