METALLOPROTEINASE INHIBITORS AND WOUND-HEALING - A NOVEL ENHANCER OF WOUND STRENGTH

Background. Wound strength is a balance between collagen synthesis and degradation. The role of collagen breakdown in wound healing is still not well understood. We investigated the role of collagenases (metall oproteinases [MMPs]) in, wound healing by using GM6001, a novel inhibi tor of MMPs. Methods. We used the dosal shin incision model with impla ntation of polyvinyl alcohol sponges. Twenty male Sprague-Dawley rats were randomly assigned to receive either GM6001 (100 mg/kg body weight ) or 2 mL saline subcutaneously. Ten days after operation the animals were killed and fresh wound breaking strength, scar and sponge hydroxy proline content, and collagen type I gene expression in sponges were a ssayed. In addition, the inflammatory response and the wound fluid cyt okine (tumor, necrosis factor-alpha [TNF-alpha] and transforming growt h factor-beta 1 [TGF-beta 1]) profile were studied. Results. GM6001 si gnificantly increased wound strength (422 +/- 59 vs 302 +/- 33 g, P < .05), whereas scar collagen content did not differ: In the sponge gran ulomas the inflammatory infiltrate, the collagen content, and the coll agen type I gene expression were all significantly decreased by GM6001 . Conclusions. Inhibition of MMP activity during acute wound healing e nhances wound strength even though new collagen synthesis and the infl ammatory response are significantly decreased. This could be achieved by decreasing collagen turnover or increasing collagen maturation and crosslinking; or both.