TY - JOUR
T1 - Metalloproteinase inhibitors and wound healing
T2 - A novel enhancer of wound strength
AU - Witte, M. B.
AU - Thornton, F. J.
AU - Kiyama, T.
AU - Efron, D. T.
AU - Schulz, G. S.
AU - Moldawer, L. L.
AU - Barbul, A.
AU - Hunt, T. K.
PY - 1998
Y1 - 1998
N2 - 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 (metalloproteinases [MMPs]) in wound healing by using GM6001, a novel inhibitor of MMPs. Methods. We used the dosal shin incision model with implantation of polyvinyl alcohol sponges. Twenty male Sprague-Dawley rats were randomly assigned to receive either GM6001 (100 mg/hg body weight) or 2 mL saline subcutaneously. Ten days after operation the animals were killed and fresh wound breaking strength, scar and sponge hydroxyproline content, and collagen type I gene expression in sponges were assayed. In addition, the inflammatory response and the wound fluid cytokine (tumor necrosis factor-α [TNF-α] and transforming growth factor-β1 [TGF-β1]) profile were studied. Results. GM6001 significantly increased wound strength (422 ± 59 vs 302 ± 33 g, P < .05), whereas scar collagen content did not differ. In the sponge granulomas the inflammatory infiltrate, the collagen content, and the collagen type I gene expression were all significantly decreased by GM6001. Conclusions. Inhibition of MMP activity during acute wound healing enhances wound strength even though new collagen synthesis and the inflammatory response are significantly decreased. This could be achieved by decreasing collagen turnover or increasing collagen maturation and crosslinking, or both.
AB - 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 (metalloproteinases [MMPs]) in wound healing by using GM6001, a novel inhibitor of MMPs. Methods. We used the dosal shin incision model with implantation of polyvinyl alcohol sponges. Twenty male Sprague-Dawley rats were randomly assigned to receive either GM6001 (100 mg/hg body weight) or 2 mL saline subcutaneously. Ten days after operation the animals were killed and fresh wound breaking strength, scar and sponge hydroxyproline content, and collagen type I gene expression in sponges were assayed. In addition, the inflammatory response and the wound fluid cytokine (tumor necrosis factor-α [TNF-α] and transforming growth factor-β1 [TGF-β1]) profile were studied. Results. GM6001 significantly increased wound strength (422 ± 59 vs 302 ± 33 g, P < .05), whereas scar collagen content did not differ. In the sponge granulomas the inflammatory infiltrate, the collagen content, and the collagen type I gene expression were all significantly decreased by GM6001. Conclusions. Inhibition of MMP activity during acute wound healing enhances wound strength even though new collagen synthesis and the inflammatory response are significantly decreased. This could be achieved by decreasing collagen turnover or increasing collagen maturation and crosslinking, or both.
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U2 - 10.1016/S0039-6060(98)70154-0
DO - 10.1016/S0039-6060(98)70154-0
M3 - Article
C2 - 9706172
AN - SCOPUS:0031828462
VL - 124
SP - 464
EP - 470
JO - Surgery
JF - Surgery
SN - 0039-6060
IS - 2
ER -