Inhibition of wound contraction with colchicine and D-penicillamine

The effects of locally injected combined colchicine and D-penicillamine on wound contraction were investigated in a murine model. Two full-thickness excisional wounds were made on either side of the back of hairless (hr/hr) mice. A volume of 0.15 ml of colchicine, D-penicillamine, or combined colchicine and D-penicillamine in normal saline vehicle were injected daily into the wound on one side of the animal and 0.15 ml of vehicle alone was injected into the wound on the other side for 5 or 10 days; thus, each animal served as its own control. The surface area of each wound was measured on Days 0, 5, and 10 to determine an index of the rate of wound contraction. At the end of the experimental period (Day 5 or 10), wounds were excised en bloc from euthanized animals for histological studies. The following histological parameters were determined: the thickness of the granulation tissue, the number of fibroblasts in granulation tissue per unit area, and the number of inflammatory cells (neutrophils, lymphocytes, macrophages, mast cells) in subjacent muscle per unit area. Our data showed that after 5 days of treatment, wound contraction was significantly inhibited only in wounds treated with combined colchicine and D-penicillamine. Wound contraction was significantly inhibited even after 10 days of treatment with the combination. Histological studies revealed that although the thickness of the granulation tissue and the number of inflammatory cells in subjacent muscle were decreased by D-penicillamine alone, only combined colchicine and D-penicillamine decreased the thickness of the granulation tissue, fibroblasts in granulation tissue, and inflammatory cells in subjacent muscle. Our data suggests that very low concentrations of colchicine and D-penicillamine when combined and injected locally may be potentially useful in controlling surface scar formation.