The effects of a broad-spectrum matrix metalloproteinase inhibitor on characteristics of wound healing.
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 microg/mL) on days 0-1 postwounding (inflammatory phase) and (b) MMP-i administration (0.03, 0.3, 3.0, and 30 microg/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 microg/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.
Klein
Scott A
SA
Department of Orthopaedic Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Anderson
Gary L
GL
Kennedy
Amy B
AB
Bond
Sheldon J
SJ
D000818:Animals; D005434:Flow Cytometry; D006909:Hydroxyproline / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008812:Mice, Hairless; D012867:Skin / Q000201:enzymology / Q000293:injuries; D019714:Tissue Inhibitor of Metalloproteinases / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D006909:Hydroxyproline