Inhibition of procollagen C-proteinase reduces scar hypertrophy in a rabbit model of cutaneous scarring.
Hypertrophic scarring, which results from excessive collagen deposition at sites of dermal wound repair, can be functionally and cosmetically debilitating to the surgical patient. Pharmacological regulation of collagen synthesis and deposition is a direct approach to the control of scar tissue formation. One of the key steps in collagen stabilization is the cleavage of the C-terminal propeptide from the precursor molecule to form collagen fibrils, a reaction catalyzed by procollagen C-proteinase (PCP). We tested the ability of a PCP inhibitor to reduce hypertrophic scar formation in a rabbit ear model. After the placement of four, 7-mm dermal wounds on each ear, New Zealand white rabbits received PCP inhibitor subcutaneously in the left ear at four time points postwounding: days 7, 9, 11, 13 (early treatment; n=20 wounds) or days 11, 13, 15, 17 (late treatment; n=20 wounds). The right ear of each animal served as a control (vehicle alone). Wounds were harvested on postoperative day 28 and scar hypertrophy quantified by measurement of the scar elevation index. Early treatment of wounds with PCP inhibitor did not reduce scar formation compared with controls (p>0.05). However, late treatment resulted in a statistically significant reduction in the scar elevation index (p<0.01). Our results point not only to the potential use of PCP inhibitors to mitigate hypertrophic scarring but also to the temporal importance of drug delivery for antiscarring therapy.
Reid
Russell R
RR
Northwestern University, Division of Plastic Surgery, Chicago, Illinois 60611, USA.
Mogford
Jon E
JE
Butt
Richard
R
deGiorgio-Miller
Alex
A
Mustoe
Thomas A
TA
D000704:Analysis of Variance; D000818:Animals; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D017439:Cicatrix, Hypertrophic / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004423:Ear / Q000293:injuries; D005260:Female; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D014945:Wound Healing / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; D008666:Metalloendopeptidases; D055395:Bone Morphogenetic Protein 1